Paper - Comparative studies on the growth of the cerebral cortex 2 (1917)
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Sugita N. Comparative studies on the growth of the cerebral cortex. II. On the increases in the thickness of the cerebral cortex during the postnatal growth of the brain. Albino rat. (1917) J Comp. Neurol. 28: 511-.
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Sugita N. Comparative studies on the growth of the cerebral cortex. II. On the increases in the thickness of the cerebral cortex during the postnatal growth of the brain. Albino rat. (1917) J Comp. Neurol. 28: 511-. Sugita N. Comparative studies on the growth of the cerebral cortex. III. On the size and shape of the cerebrum in the Norway rat (Mus norvegicus) and a comparison of these with the corresponding characters in the albino rat. (1918) J Comp. Neurol. 29: 1-. Sugita N. Comparative studies on the growth of the cerebral cortex. IV. On the thickness of the cerebral cortex of the Norway rat (Mus norvegicus) and a comparison of the same with the cortical thickness in the albino rat. (1918) J Comp. Neurol. 29: 11-. Sugita N. Comparative studies on the growth of the cerebral cortex. V. Part I. On the area of the cortex and on the number of cells in a unit volume, measured on the frontal and sagittal sections of the albino rat brain, together with the changes in these characters according to the growth of the brain. V. Part II. On the area of the cortex and on the number of cells in a unit volume, measured on the frontal and sagittal sections of the brain of the Norway rat (Mus norvegicus), compared with the c responding data for the albino rat. (1918) J Comp. Neurol. 29: 61-117. Sugita N. Comparative studies on the growth of the cerebral cortex. VI. Part I. On the increase in size and on the developmental changes of some nerve cells in the cerebral cortex of the albino rat during the growth of the brain. VI. Part II. On the increase in size of some nerve cells in the cerebral cortex of the Norway rat (Mus norvegicus), compared with the corresponding changes in the albino rat. (1918) J Comp. Neurol. 29: 119-. Sugita N. Comparative studies on the growth of the cerebral cortex. VII. On the influence of starvation at an early age upon the development of the cerebral cortex. Albino rat. (1918) J Comp. Neurol. 29: 177-. Sugita N. Comparative studies on the growth of the cerebral cortex. VIII. General review of data for the thickness of the cerebral cortex and the size of the cortical cells in several mammals, together with some postnatal growth changes in these structures. (1918) J Comp. Neurol. 29: 241-.
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Comparative Studies on the Growth of the Cerebral Cortex
II. On the Increase in the Thickness of the Cerebral Cortex during the Postnatal Growth of the Brain. Albino Rat
From The Wistar Institute of Anatomy and Biology
Twelve Figures And Twelve Charts
I. Introduction
The object of this paper is to present the data collected upon the increase in the thickness of the cerebral cortex of the albino rat from birth to maturity and so to give an insight into the postnatal growth of one important portion of the cerebrum. A study of this kind may be of value in several ways: It should be of fundamental biological interest, it should be useful for reference in experimental work on the central nervous system and in connection with extensive data on the rat collected by Donaldson ('15), and finally it should shed some hght on comparative psychology.
Papers on the thickness of the cerebral cortex of the mature human brain have been published by several anatomists, for example, Schwalbe ('81), Donaldson ('91), Hammarberg ('95), Kaes ('05, '07), Brodmann ('09), etc. His ('04) has also carefully described the developmental changes of the cerebral cortex in the early fetal period of the human brain, including the cortical thickness. Furthermore, there has been only one study on the development of the human cortex after birth, a paper by Kaes ('07) which, however, is unfortunately open to very serious criticism. Brodmann ('09) has made an extensive collection of results obtained by comparative anatomists on the cerebral cortex in several orders of the mammals. It is not possible, however, to compare the results in these valuable papers, because, the authors are not in accord in respect to technical methods or the localities where the thickness was measured. My intention in the study which follows is to present the results of the exact measurements systematically applied to the thickness of the cerebral cortex during postnatal growth, using ample material and treating this with uniform methods of dissection, fixation, imbedding and staining. The systematic examination of sections thus prepared should make it possible to trace the steps in the growth of the cerebral cortex of the albino rat from birth to maturity in a way which could be controlled by subsequent workers in this field.
Hitherto, there has been no systematic study in this field so that I have not had any previous example to follow. I have therefore used my own judgment as to the localities to be sectioned and the methods of measurement. The reasons for the various methods will be given in the appropriate chapters. In a later part of this series of studies, I shall try to review collectively the data presented by previous authors concerning the cortical thickness of human and animal brains. As these researches have, however, been all directed towards the solution of phylogenetic problems and have been made on the adult individual, they have but little immediate bearing on the present problem.
In connection with this research, and using the same material, I have studied also the developmental changes during growth in the size and shape of the ganglion cells, the differentiation of the cell-layers of the cortex, the distribution of the several kinds of ganglion cells in the cerebral cortex, and further, the changes in the relations between the elements of the central nervous system according to the growth phase of the brain. These results Avill be presented in papers which are to follow.
This study was started in October, 1915, and completed in June, 1916, under the direction of Prof. H. H. Donaldson at The Wistar Institute of Anatomy and Biology and I am much indebted to Prof. Donaldson for his valuable suggestions.
II. Material
The animals used in the present study were all from the rat colony of The Wistar Institute. I employed 124 albino rats, 96 males and 28 females, representing every stage of postnatal growth and having approximately standard body weights. After .dissection, the entire brain was separated from the spinal cord by a section at the level of the calamus scriptorius and was weighed in a small weighing bottle. I have classified the individuals in twenty groups, according to the number of decigrams in the brain weight of each, for example, brains weighing 0.300 to 0.399 grams form Group III and brains weighing 1.500 to 1.599 grams. Group XV, etc. In each group, the individual was designated as a, b, c in the order of the date of the dissection. The body and brain weights, body and tail lengths, sex and age of each individual are given in tables 1 and 2. The measurements were made by the usual methods employed at The Wistar Institute.
My reason for classifying the material according to brain weight, is that my own observations as well as those of others have shown that the brain weight increases most regularly according to age, and is much more resistant to outside influences than the body weight, for example. Hence it seemed to me to be not only more cojivenient, but also more precise to arrange the material according to the brain weight, rather than according to the body weight, or some other physical character.
Tables 1 and 2 show the sex, body and tail lengths, body and brain weights of the albino rats used in this study on the thickness of the cerebral cortex (table 1) in the sagittal and the frontal sections and (table 2) in the horizontal sections respectively, entered in the order of the increasing brain weight.
These animals were collected at random from many different litters and at various seasons. iVlthough individual variations appear when the data are compared with the values in the reference tables for the rat (Donaldson, '15), nevertheless, by grouping these data according to the number of decigrams of brain weight, and obtaining the average values, it is found that these
TABLE 1
Showing the sex, body and tail lengths, body and brain weights of the albino rats used in this study on the thickness of the cerebral cortex in the sagittal and frontal sections, entered according to increasing brain weight
NITMBEK
SEX
AGE
BODT WEIGHTl
BODY LENGTH
TAIL LENGTH
BRAIN WEIGHT
days
groTns
mTn.
tiiTn.
grama
la
2.9
38
14
0.1-53
c
2.9
34
14
0.154
b
3.2
42
15
0.177
II a
m
B
4.8
47
16
0.213
b
m
B
4.6
45
16
0.221
c
m
B
5.0
48
19
0.261
d
m
B
5.0
51
18
0.271
e
m
1
5.7
50
18
0.288
Ilia
m
2
5.5
50
17
0.311
b
f
3
5.2
49
18
0.322
g
m
4
7.1
55
23
0.374
c
m
3
6.5
54
20
0.390
i
f
4
5.7
53
22
0.395
IV b
m
4
7.2
56
22
0.400
a
m
4
6.8
54
22
0.402
c
m
5
7.6
56
22
0.420
i
m
4
6.6
57
23
0.443
d
m
5
8.9
59
26
0.459
e
m
5
9.8
60
25
0.466
Vi
m
5
8.2
61
25
0.501
a
m
5
8.3
58
25
0.525
b
f
7
8.5
61
26
0.528
c
m
6
12.2
63
30
0.534
d
m
7
10.9
65
27
0.537
e
m
6
8.2
60
25
0.555
f
m
6
8.8
60
30
0.558
g
m
6
8.5
57
25
0.564
h
f
7
10.5
63
29
0.579
Vic
m
7
8.5
62
28
0.610
a
m
7
12.1
63
26
0.617
e
f
8
8.6
61
29
0.690
Vila
m
9
8.4
61
32
0.740
b
m
8
8.9
62
33
0.760
GROWTH OF THE CF-REBRAL CORTEX
515
TABLE 1— Continued
NUMBER
SEX
AGE
BODY weight'
BODY LENGTH
TAIL LENGTH
BBAIN WEIGHT
days
grams
niTn*
mm.
grams
Villa
m
9
12.2
66
30
0.800
h
m
9
8.9
61
32
0.805
b
m
9
10.8
67
32
0.822
c
m
10
12.4
68
36
0.849
k
m
11
11.6
69
39
0.870
d
f
10
13.9
70
30
0.898
IX d
m
11
13.3
73
38
0.959
e
f
12
14.6
79
42
0.960
a
m
11
14.1
75
40
0.972
Xa
m
12
15.2
74
45
1.033
b
m
13
15.8
77
43
1.036
e
m
15
15.5
73
49
1.051
XI a
m
17
13.4
75
51
1.107
b
m
22
20.4
82
46
1.189
c
m
15
15.8
79
47
1.193
d
m
20
18.7
80
58
1.195
XII c
m
25
20.5
84
54
1.234
a
f
28
35.4
103
88
1.273
XIII a
m
16
20.4
82
60
1.301
g
m
40.9
120
692
1.307
b
m
30.6
102
•85
1.327
c
m
29.8
106
73
1.346
h
f
28
38.5
114
90
1.392
XIV a
m
32.1
108
77
1.412
e
m
77.4
144
130
1.441
b
m
30
38.1
110
86
1.483
XV a
m
50
77.8
142
135
1.530
b
f
35
54.9
127
119
1.542
c
f
60
79.4
140
134
1.552
d
f
41
70.1
139
120
1.573
e
f
60
66.7
138
123
1.574
XVI a
m
105
121.0
167
151
1.642
g
f
163.0
191
173
1.643
c
f
216.83
198
170
1.647
e
m
145.0
178
147
1.690
516
NAOKI SUGITA
TABLE 1— Concluded
NUMBER
SEX
AGE
BODY WEIGHTl
BODY LENGTH
TAIL LENGTH
BRAIN WEIGHT
days
fframs
mm.
mm.
grams
XVII f
f
234.0
201
174
1.720
a
m
77
119.5
.163
150
1.721
b
m
90
123.0
169
141
1.730
c
f
108
125.3
162
150
1.731
XVIII c
m
112
204.7
195
160
1.817
a
m
150
191.0
192
165
1.844
e
m
112
210.0
198
164
1.855
XIX a
m
2 years
300.2
225
195
1.924
XX a
m
2 years
251.5
162^
215
2.039
b
m
2 years
321.0
180*
187
2.069
1 Under 10 grams net weight, over 10 grams gross weight given.
2 Cut.
^ Pregnant.
■• Because of rigor mortis, this figure is not reliable. .
average values are in fair accord with the reference table values as shown in tables 3 and 4, corresponding respectively to tables 1 and 2.
These latter values have been obtained by the use of the formulas devised by.Hatai and given in The Rat" (Donaldson, '15). A comparison of the observed and calculated values shows that in the case of Groups II-XV in table 3 and Groups II-XIII in table 4, the agreement is close, and as these groups go up to 30 days of age or more they include the period in which there is any important increase in the thickness of the cortex. After 30 days of age the discrepancies which appear between the observed and corftputed body weights and body and tail lengths are not significant for the present investigation and may therefore be neglected.
GROWTH OF THE CEREBRAL CORTEX
517
TABLE 2
Showing the sex, body and tail lengths, body and brain weights of the albino rats used in this study on the thickness of the cerebral cortex in the horizontal sections, entered according to increasing brain weight
NUMBER
SEX
AGE
BODT WEIGHT
BODY LENGTH
TAIL LENGTH
BRAIN WEIGHT
days
grams
mm.
mm,.
grams
II f
m
1
5.5
50
21
0.288
g
m
2
6.9
53
19
0.296
III d
m
1
6.1
52
22
0.303
f
m
2
5.9
53
20
0.318
e
m
2
6.1
50
22
0.331
IV g
m
3
6.4
53
23
0.415
h
m
3
6.9
54
23
0.421
f
m
5
8.4
60
24
0.423
V j
m
5
9.9
63
29
0.520
1
m
5
9.1
61
27
0.535
k
m
7
11.3
63
28
0.541
n
m
■7
10.6
63
28
0.563
m
m
7
11.6
63
30
0.569
VI d
m
7
9.0
62
28
0.613
b
m
7
8.7
63
28
0.650
VII d
m
8
9.9
64
29
0.728
c
m
7
9.3
63
32
0.794
VIII e
m
10
12.1
68
33
0.809
i
m
8
8.3
62
32
0.829
f
m
10
13.2
69
33
0.868
g
f
9
18.9
80
41
0.884
IX b
m
11
13.8
71
39
0.914
c
m
12
13.6
73
40
0.964
X d
f
11
15.1
75
48
1.028
c
m
12
15.6
77
44
1,035
f
m
14
15.2
79
45
1.098
XI e
m
16
16.2
78
50
1.121
XII d
m
20.9
84
51
1.209
b
f
21.3
82
60
1.255
e
m
23.9
92
78
1.257
518
NAOKI SUGITA
TABLE 2— Concluded
NUMBER
SEX
AGE
BODY WEIGHT
BODY LENGTH
TAIL LENGTH
BRAIN WEIGHT
days
grams
mm. •
tmn.
grams
XIII d
111
21,9
84 •
62
1.332
f
111
33
25.1
96
77
1.344
e
f
28.3
100
82
1.377
XIV d
f
76.7
135
125
1.448
c
m
54.9
126
93
• 1.461
XV f
f
50
83.0
152
135
1.533
g
f
86.5
147
140
1.599
XVI b
m
68
130.0
164
150
1.674
h
f
188.7
189
175
1.675
d
f
95.7
151
136
1.680
f
m
252.2
202
188
1.683
XVII e
f
168.5
190
162
1.723
d
m
184.0
195
156
1.738
XVIII 1)
f
127.5
168
157
1.802
d
111
112
188.4
188
152
1.844
XX c
m
2 years
295.0
203
194
2.004
III. Technique
Fixation
For the exact measurement of the thickness of the cerebral cortex, it js desirable to have material which has suffered the least possible change in volume as result of fixation and also to employ a uniform technique. As a preliminary, I went over King's work ('10) on the effects of various fixatives on the adult albino rat brain, applying several kinds of fixing fluids to brains in different stages of growth, and imbedding them in parafiine. These brains were sectioned and the cell pictures studied under the microscope to determine the influence of the several fixatives upon the cells and the surrounding tissues. War conditions prevented the use of celloidin and photoxylin as imbedding media to be compared with parafiine.
TABLE 3
Showing the average age, body weight, body and tail lengths and brain weight grouped by brain weight of the albino rats used in this study for sagittal and frontal sections, accompanied by the calculated standard age, body weight, body and tail lengths corresponding to the given brain weights
OBSERVED
CALCULATED
standards'
GROUP
Age
Body
weight
ody length
Tail
length
Brain weight
Tail length
Body length
Body weight
Age
days
grartis
mm.
mm.
grams
mm.
mm.
gra7ns
days
I
3.0
38
14
0.161
— .
— .
— ■
—
II
B+
5.0
48
17
0.251
17
49
5.0
B+
III
3+
6.0
52
20
0.358
25
56
6.1
2+
IV
5
7.8
57
23
0.432
27
58
6.8
4
V
6+
9.3
61
27
0.542
31'
62
8.0
6
VI
7+
9.7
62
28
0.639
35
65
9.2
7—
VII
9
8.7
62
33
0.750
39
69
10.9
8+
VIII
10
11.6
67
33
0.841
42
71
11.8
9
IX
11 +
14.0
76
40
0.964
47
76
13.3
11
X
13+
15.5
75
46
1.040
51
80
15.6
14+
XI
19
17.1
79
51
1.171
60
89
20.4
21 +
XII
27
28.0
94
71
1.253
68
96
25.0
26+
XIII
32.0
105
77
1.335
78
105
31.3
32
XIV
49.2
121
98
1.445
93
121
44.0
41
XV
49+
69.8
137
126
1.554
110
138
63.0
52
XVI
143.01
1791
1571
1.656
129
157
91.2
64+
XVII
150.5
174
154
1.726
142
171
117.6
75
XVIII
125
201.9
195
163
1.839
165
196
179 6
110+
XIX
2 years
300.2
225
195
1.924
183
215
250.5
205
XX
2 years
286.3
201
2.054
212
246
417.5
1 Pregnant one omitted.
- Rigor mortis.
' All calculated by formulas for sexes combined.
As a result, Bouin's fluid (picric acid solution in water at room temperature, saturated, 75 vol., formalin 25 vol. and glacial acetic acid 5 vol.) was selected as most suitable for the present work. When the rat brain is fixed in this fli»id for 24 hours, the shape and the weight of the total brain suffer but little, if any, change, as the result of the fixation. The other fluids commonly used for fixation either swell or shrink the brain very noticeably (King, '10). On comparing the sections obtained from brains fixed in other fluids with those fixed in Bouin's fluid,
TABLE 4
Showing the average age, body weight, body and tail lengths and brain weight grouped by brain weight of the albino rats used in this study for horizontal sections, accompanied by the calculated standard age, body weight, body and tail lengths corresponding to the given brain weights
OBSERVED
CALCULATED
STANDARDS
GROUP
Age
Body weight
Body length
Tail length
Brain weight
Tail length
Body leng:>h
Body weight
Age
days
grams
mm.
mm.
grams
mm.
mm.
grams
days
II
2
6.2
52
20
0.292
22
54
5.5
1 +
III
2
6.0
52
21
0.317
23
55
5.7
2
IV
4
7.2
56
23
0.419
27
58
6.6
3+
V
6+
10.5
63
28
0.546
31
62
8.1
5+
VI
7
8.9
63
28
0.631
35
64
9.1
7
VII
8
9.6
64
31
0.761
40
69
11.0
8+
VIII
9+
13.2
70
35
0.848
42
71
11.9
9+
IX
12
13.7
72
40
0.939
46
75
13.3
10
X
12+
15.3
77
46
1.054
52
80
16.0
15
XI
16
16.2
78
50
1.121
56
85
18.3
18+
XII
—
22.0
86
63
1.240
67
95
24.1
25+
XIII
—
25.1
93
74
1.351
80
107
32.7
33
XIV
—
65.8
131
109
1.455
94
122
45.3
42
XV
—
84.8
150
138
1.566
111
139
64.0
53+
XVI
—
166.7
177
162
1.678
133
162
99.0
68
XVII
—
176.3
193
159
1.730
143
172
119.0
75+
XVIII
—
158.0
178
155
1.823
162
192
170.0
102+
XX
2 years
295.0
203
194
2.004
200
233
340.0
—
I was convinced that, for the present study, the latter should be exclusively used (cf. also Allen, '16).
From an examination of the cell bodies and nuclei, I have concluded that they were not much modified by either swelHng or shrinkage. The sections fixed with Bouin's fluid are, however, less well stained with Nissl's soap-methylene-blue-solution, toluidin blue or thionine than the sections fixed with formalin or alcohol. But, if .carbol-thionine solution (1 gram thionine powder dissolved in 99 cc. of 0.5 per cent aqueous solution of carbolic acid) be used as the stain, this defect is remedied, and in the rat brain at least, tl^ey stain distinctly.
As a result of these preliminary tests the sections used for this study were all prepared by the methods just described and in doing this, the procedure outlined in the next section was followed.
The method of procedure
The rat was chloroformed and its sex, body and tail lengths and body weight recorded. After complete evisceration, the brain was exposed and the pia mater carefully removed from the surface of the brain. Then the entire brain was severed from the cord by a transverse section at the level of the calamus scriptorius and taken out, care being taken to preserve the paraflocculi and the olfactory bulbs. The brain was put on a glass plate, basal surface down and without lateral support. The five diameters of the hemispheres were next measured — according to the method described in the first paper of this series (Sugita, '17) — this procedure being desirable not only for the present study but also for a study on the changes in the size and shape of the brain according to age. The total brain was then put into a closed weighing bottle and weighed to the tenth of milligram. The brain was next transferred to Bouin's fluid for 24 hours at the room temperature, the basal surface of the brain being in even contact with the bottom of the vessel. After fixation, the brain was washed with running water for 20 minutes and then put into 20 cc. of 80 per cent alcohol for 24 hours and into 20 cc. of 90 per cent alcohol for 24 hours successively, for dehydration and further fixation. On the occasion of each change of fluid the diameters of the hemispheres were measured and the total weight taken in order to record the modifications produced.
With india ink and a fine brush lines were circumscribed on the surface of the brain in order to designate the planes from which sections should be taken after imbedding. The positions of these lines will be described in the following chapter. Slices about 2 mm. in thickness and including the level from which the sections were to be taken, were made, and placed in 10 cc. of absolute alcohol for 6 hours, then in xylol for one and a half hours at the room temperature, transferred into the xylol-parafine mixture for one and a half hours in the oven at 37°C., and finally imbedded in parafiine for two hours at about 56°C. I have used the paraffine with the melting point at 54°C. in winter time and that at 56°C. in summer time, for the convenience of making sections.
A series of sections 10 micra thick was cut exactly from the designated level, adjusting the microtome carefully to this end, and these sections were affixed on the glass slide by the albuminglycerine method. After the sections had dried in the oven overnight at 37°C., they were washed in the xylol bath, in order to dissolve away the paraffine from the sections, and then again washed with absolute alcohol to remove the residual xylol. After having passed through the several grades of alcohol, they were brought to the water bath, and kept there until the yellow tone of the sections due to the picric acid in Bouin's fluid totally faded away. Now the sections were placed in the carbol-thionine solution above described and remained there for two hours at room temperature. After being washed slightly with running water, and passed through 70 per cent, 80 per cent, 90 per cent, 95 per cent and absolute alcohols successively, each for a short time, in which they were not only dehydrated but at the same time decolorized, they were cleared in xylol or carbol-xylol and, at last, mounted in the neutral Canada balsam.
Examination of sections
The sections were each projected on a sheet of paper by the Leitz-Edinger projection-apparatus, at a magnification of twenty diameters exactly. The outline of the image was then accurately traced on the sheet, and, perpendicular to the braii;! surface, fines were drawn parallel to the radiations of the cortex at several selected localities, at which the thickness of the cortex was to be measured. These localities are shown on the figures which will be described in the following chapter. The length of the line between the external margin and the lowest cell-layer of the cortex, where it is in contact with the white matter, was measured with the sfiding calipers accurately to a tenth of a millimeter, and one twentieth of this value was recorded as the actual thickness of the cortex on the sfide at this locality.
Two or more measurements of each locality on a given section were always made and, where these differed, the mean value was recorded. The same locality measured on the different sections from one and the same series, taken from a given slice, showed for the most part some differences in thickness, though never large differences. The main reasons for these differences appear to be the following:
1. As 6 to 12 sections were taken in succession from a given sUce, at the level of the mark of india ink, these sections should not be identical as to thickness of the cortex, owing to the fact that the surface of the hemisphere is, of course, not strictly vertical to the plane of the section. Changes in cortical thickness due to this cause are, in general, very slight.
2. Although the outer boundary of the cortex is very distinct, the borderline between the cortex and the white substance is not equally sharp and this may prove a source of slight error in determining the thickness of the cortex. Direct tests indicate a variability of less than one-half of 1 per cent plus or minus, so that this error may be neglected.
3. In the procedure of attaching sections to slide by means of albumin-glycerine, the sections were first warmed over a small flame, in order to unfold and flatten them. During this manipulation, slight differences of extension sometimes occur in consequence of the dissimilarity of the temperature used. If the temperature be a little higher than the melting point of the paraffine, sections extend at first much, and, when they are cooled, they may shrink rather suddenly, thereby reducing the size of sections below that found before heating. If the temperature be raised only just to the melting point, or a little below it, the size of the sections on slide will be quite unmodified, but it is not always easy to control the temperature precisely, and significant alterations in the size of the sections due to this influence do occur. With a view to adjusting these differences, a method of correcting the direct observations was devised and the manner in which the correction was applied will be given in a later chapter.
IV. The Sections
Sagittal sections
Alter complete fixation of the brain, the sagittal sections were obtained by slicing the right hemisphere in a plane parallel to the mesial surface. The cut passes through the frontal point (S), as shown in figure 1 diagrammatically, and touches tangentially the lateral boundary of the infundibulum, while passing sagittally through the olfactory bulb. The plane of this cut is marked with India ink on the brain, by a circumscribing
Fig. 1 Diagram of the entire brain of the albino rat seen from above, showing the levels from which the sagittal and frontal sections were taken. SS', the sagittal section; FF', the frontal section; 0, middle point of the sagittal fissure.
hne SS' around the parietal and basal surface of the right hemisphere, along which the sagittal section is to be taken, and a slice of the hemisphere, about 2 mm. in thickness, containing the delineated plane in the middle, is cut out and imbedded in paraffine as previously described. From this slice and exactly in the plane determined by the circumscribing line, 6 to 12 sections were cut in series, stained and mounted. From the left hemisphere of the same brain, frontal sections were also taken. Figure 2 is a somewhat diagrammatic picture of the sagittal section from the albino rat brain at about thirty days in age, and is intended to show the cell-lamination of the cortex and the localities at which the thickness of the cortex was measured. Cytoarchitecturally the cortex of the sagittal section is divided into several areas characterized by the difference of celllamination.
The cerebral cortex of the albino rat has five cell layers (fig. 3) if a typical locality be taken. The most external layer is the lamina zonalis (I), which has a few scattered glia-cells. Under this, there is the lamina pyramidalis (III) consisting of typical, deeply-staining, pyramidal cells lying closeh^ together, which corresponds to the third layer of Brodmann ('09). In the rodent brain, the lamina granulans externa (II), or the second layer of Brodmann, is always indistinct, and it is almost impossible to distinguish it from the lam. pyr. (III). Beneath the lam. pyr., the lamina granular is interna (IV) is situated, composed of crowded, deeply-staining, small granules, somewhat resembling glia-cells. Below this laj^er, there is the lamina ganglionaris (V), which has dispersed, large-sized, deeply-staining pyramids. Next to the lam. gang., there is the lamina multiformis (VI) with polymorphous cells.
Fig. 2 Diagram of the sagittal section, from the albino rat brain weighing 1.5 grams, at about 30 days in age, showing the cell-lamination of the cortex and the localities at which the thickness of the cortex was measured. //' is the level from which the frontal section was to be taken. Lines AA', BB', CC, DD', EE' and FF' indicate the borders of the areas showing different types of cell-lamination.
In the sagittal section (fig. 2) the cortical area lying between A A' and BB', — A A' marking the knee where the gray of the olfactory bulb passes over to the frontal cerebral cortex and BB' marking almost the middle of the parietal cortex covering the lateral ventricle, — is distinctly provided with all the five cell layers (fig. 3). The lam. zon., the lam. pyr., and the lam. gang, are all typically constructed. In the lam. gran, int., especially in material fixed in formol, the tissue surrounding the granules may stain deeply, giving by low-power magnification the appearance of a distinctly stained band, but this appearance is not so evident in the material fixed in Bouin's fluid. The lam. gran. int. may be distinguished from the lam. pyr. by the fact that in the former the cells are small and crowded densely. There is a narrow band poor in cells, between the lam. gran. int. and the succeeding lam. gang. The lam. mult., in the albino rat, is distinctly separated into two sublayers by a narrow, light band very poor in cells. The broader (ectal) sublayer which lies immediately below the lam. gang, is rich in cells, about equal in size to the cells of the lam. pyr., but slightly less stained. The narrower (ental) sublayer which lies under the band poor in cells forms the boundary to the white substance, and consists of polymorphous cells, somewhat larger in size than the small pyramids and tinted a little more deeply. In the area AA'-BB' , the lam. mult, is the thickest layer and it occupies more than onethird of the total thickness of the cortex. The lam. gang, is the next in thickness, almost equal to the sum of the thickness of the laminae pyr. et gran. int. The lam. gran. int. is the thinnest.
I. Lamina zonalis.
I III. Lamina pyramidalis.
1 IV. Lamina granulans interna.
v. Lamina ganglionaris.
Ectal sublayer'
Ental sublayer J
Lamina multiformis.
Fig. 3 Diagram of the typical cerebral cortex of the albino rat, for illustration of figures 2, 4 and 6.
The small area between BB' and CC has almost the same cell lamination as the area AA'-BB' , but the cortex of this area becomes thinner towards the occipital pole. Especially the lam. gang, loses in thickness remarkably. The characteristic of this area is the appearance in the lam. gang, of the giant pyramids, representing the largest nerve cells in the cerebral cortex of the rat.
The area CC'-DD', — DD' marking the occipital pole of the cortex — covers as a cap the cornu Ammonis. In it, the total thickness of the cerebral cortex diminishes on the average to a half of that in the area AA'-BB'. In this area, the lam. pyr. and the lam. gran. int. do not show much difference as compared with the foregoing areas, the cells of the both layers staining deeply. The lam. gang., however, becomes very narrow in this area, and, in addition to this, the size of pyramids is much reduced. The lam. mult, loses greatly in thickness, but the character of the cells remains unchanged. Near the occipital pole {DD') the light band which divides the lam. mult, into two sublayers disappears.
The area DD'-EE' shows a quite characteristic cell-lamination, for example, the lam. zon. thickens distinctly while the laminae pyr. et. gran. int. thicken suddenly at the part, where the cortex is turned over the occipital pole and the surface of the hemisphere makes contact with the dorsal surface of the corpora quadrigemina. Immediately beneath the lam. gran, int. comes the lam. mult., the lam. gang, almost vanishing for a while. The lam. mult, exhibits, in this area, one layer instead of two.
The area EE'~FF' represents the subiculum cornu Ammonis. The cortex consists of a thick lam. zon., the lam. gang, which has again resumed its former breadth, and the very thin lam. mult. At FF' the pyramids of the lam. gang, come more closely together, and the breadth of the layer diminishes remarkably, the cells arranging themselves in about three or four rows, as they pass over to the specific ganglion cell layer of the cornu Ammonis.
Figure 2 shows also the positions of the localities at which the thickness of the cerebral cortex was carefully measured. These localities have been so selected as to be fairly representative of the entire cortex as regards thickness.
Locality I. On the line of /-/', drawn through the frontal tip and running parallel to the radiation of the ganglion cells, the diameter /-/' is measured, between the outer limit of the lam; zon. and the inner border of the lam. mult. As a matter of fact, the cell-radiation in this locality is not exactly in a straight line, but somewhat bent, owing to the rapid curvature of the cortex and its great thickness. Notwithstanding this, I have measured the thickness of the cortex by a straight line, as indicated above. The thickness at /-/' is the greatest found in this study.
Locality V. The thickness V-V is measured at a point somewhat cephalad to the occipital pole, on the line directed along the cell-radiation. I thought it would be more advisable to measure the occipital cortex not exactly at the tip of the occipital lobe, but somewhat cephalad, thus making the direction of the line V-V not very divergent from the direction of the line IV-IV , if not parallel to it. The locality chosen {V) seemed suitable and has been used throughout. The thickness at V~V' represents the thinnest part of the cortex.
Locality III is midway between localities I and V and falls nearly in the middle of the area BB'-CC , the area in which the largest pyramidal cells appear. The locality is marked by the line III-III' , drawn perpendicular to the cortex and tangent to the ganglion-cell band at the frontal tip of the cornu Ammonis.
Locality II. The line at II-IF runs parallel with the radiating cells and lies midway between the localities I and III. The line II-II' was drawn so that the distance between the middlepoints of the lines /-/' and II-II' is equal to the distance between the middle-points of the lines II-II' and II-II I', when the distances are measured along the cell band of the lam. gang. Locality II represents the central part of the area AA'-BB'.
Locality IV. The line IV-IV is drawn midway between positions of the localities III and V, determined in the same manner as the position of the line II-II'. This locality represents the central part of the area CC'-DD'.
The lines /-/' and II-II' represent the thickness of the cortex m the area AA'-BB', the lines IV-IV and V-V the thickness of the cortex in the area CC'-DD', and through the increments in the lengths of these lines according to growth the development of the frontal and occipitals parts of the cortex of the rat brain as they appear in this plane may be determined.
For convenience of comparison in the final statement I have averaged the values of the above named five measurements and this is designated as the average thickness of the cerebral cortex in the sagittal section."
Frontal sections
In figure 2 the line ff' marks the part of the brain from which the frontal sections were taken (FF' fig. 1). The frontal sections were obtained by cutting the hemisphere in a plane passing through approximately the middle point of the mesial surface, the corpus callosum, the commissura anterior and the chiasma opticum (fig. 1). For the frontal sections the left hemisphere of the same individual, from which the sagittal sections of the right hemisphere had been taken, was used. The technical procedure was similar to that used for the sagittal sections.
Figure 4 is the general diagram of the frontal section, from the albino rat brain, about thirty days of age, and illustrates the cell-lamination and the positions of the cortical localities which were measured. The cortex of the frontal section shows several areas characterized by the structure of the cell layers.
At the bottom of the sagittal fissure appears a small area, where only a few cells, probably of the lam. mult., are to be seen (indusium). Next to this, comes the area GG'-HH' , GG' marking the mesial tip of the cortex, and HH' the knee of the cortical cm-vature. This area has all the layers at HH', but all except the lam. mult, disappear at GG'.
Fig. 4 Diagram of the frontal section, from the albino rat brain weighing 1.5 grams, at about 30 days in age, showing the cell-lamination of the cortex and the localities at which the thickness of the cortex was measured, ss', plane in which the sagittal section was taken; hh', level from which the horizontal section was taken. Lines GG' , HH', KK', LL', MM', NN' and 00' indicate the borders of the areas showing different types of cell-lamination. TV' fissura rhinalis. Between M and N the claustrum — (CO— is seen. Gr.? marks the unidentified cell group between AW and 00'.
In the area HH'-KK', the radiation of the cells is perpendicular to the curved surface of the cortex, and the lam. mult, is formed of a single layer. This area is here noted, because the locality VI is in the middle of it and the line VI~VI' passes through the tip of the curvature.
The area KK'-LL' corresponds to the part, from which the sagittal sections were cut, and shows distinctly the five layers. In this area the lam. mult, is divided by a pale band into two sublayers. The cells of the lam. pyr., the lam. gran, int., the lam. gang, and the ental sublayer of the lam. mult, are all stained deeply, but the cells of the ectal sublayer of the lam. mult, are stained somewhat paler. The lam, gang, is here relatively broad, occupying about one-third of the total thickness of the cortex while the laminae pyr. et gran. int. are relatively thin.
In the area LL'-MM' , representing the greater part of the cortex in the frontal section, the laminae pyr. et gran. int. are on the whole much thicker than in the areas just described, and the granules especially are densely crowded. In the material fixed in formol, as remarked already, the intercellular tissue of the lam. gran. int. takes the stain so well, as to show apparently a deeply stained band by a low magnification. The lam. gangbecomes thin as the laminae pyr. et gran. int. increase, and finally becomes thinner than the sum of both these layers. The lam. mult, is divided into two sublayers, as was seen in the sagittal section, and its relative thickness does not vary greatly.
At the fissura rhinalis, denoted by A, the lam. zon. thickens markedly, while the total thickness of the other layers diminishes. In the area MM'-AN', the claustrum is seen at the bottom of the cortex, covered by the lam. mult. Just ventrad to the line MM', the two sublayers of the latter fuse into a single layer and no special layer exists between this and the claustrum (CI).
Between AA' and 00', the polymorphous cells of the lam. mult, are scattered and dispersed and, beneath the lam. mult., a cell group is seen, composed of large-sized, deeply-staining cells, which are hardly distinguished from the cells of the ental sublayer of the lam. mult. The pyramids of the lam. pyr. are here more crowded together and make a wavy band. Beneath this in a single layer, scantily scattered, the small cells of the lam. gran. int. and the large pyramids of the lam. gang., are seen. There is a pale broad band between this layer and the above-mentioned cell group {Gr.f).
Aledian to 00', there is the tractus olfactorius ectal to the ' lam. pyr., which latter has been thrown into waves.
Figure 4 shows also the three locaUties, at which the thickness of the cortex has been measured.
Locahty VI. The line VI~VI' starts from the tip of the dorsomesial curve of the pallium perpendicular to the surface and runs parallel to the cell radiation. This line represents the cortical thickness in the area HH'-KK' , where the laminae pyr. et gran, int. are so thin that the sum of the both layers does not amount to one-seventh of the total thickness of the entire cortex. The lam. gang, is somewhat thicker than the lam. mult, and the latter becomes a single layer just at this point.
Locahty VII. The line VII-VII' has been drawn at the middle of the area LL'-MM'. In this area the laminae pyr. et gran. int. have increased in thickness, so as to amount to about one-third of the total thickness of the cortex, while the lam. gang, has undergone a corresponding diminution.
Locahty VIII. The line VIII-VIII' is measured at the bottom of the fissura rhinalis.
The thickness of the cortex in the frontal section is greatest at Vll-Vir, and least at VIII-VIII', the level of the fissura rhinalis, while the thickness at VI-VF is intermediate.
For convenience of comparison I have averaged the values of the three thicknesses and named this the "average thickness 9! the cerebral cortex in the frontal section."
Horizontal sections
In figure 4 the line hh' indicates the level from which the horizontal sections were taken (HH' fig. 5). The horizontal sections were made by cutting through the entire brain in a plane approximately parallel to the basal surface of the brain and passing through the frontal poles of both hemispheres and the points at which the occipital poles and the paraflocculi touch (fig. 5) . In the young rat brain, this section is tangent to the dorsal surface of the bulbus olfactorius. In adults, however, it cuts somewhat obliquely through the bulbs, because, owing to the rapid development of the cerebellum in the early days of life, the paraflocculi, used as the marking points, extend dorsad, causing an upward shift of the occipital end of the plane of section. The technique used in obtaining the horizontal sections was similar to that employed for the sagittal and frontal sections.
Fig. 5 Diagram of the entire brain of the albino rat, seen from the side and showing the level from which the horizontal sections were taken. HH', horizontal section.
Fig. 6 Diagram of the horizontal section, from the albino rat brain weighing 1.5 grams, indicating the position of the localities measured on the section and the cortical cell-lamination. //' and ss' show respectively the levels from which the frontal and the sagittal sections were taken. The lines PP', QQ', RR', SS', TT', UU', WW, X' and YY' indicate the borders of areas which show differences of cell-lamination and V indicates the rhinal fissure.
Figure 6 gives a schematic view of a horizontal section in this plane, from the albino rat at about thirty days of age. It shows diagrammatically the cell structure of the cortex and the positions of the localities subjected to measurement. The cortex of the horizontal section is divided into areas as follows.
The small area median to PP' , lying at the bottom of the sagittal fissure between the two hemispheres, corresponds to the similar area median to GG' in the frontal section (fig. 4), which consists only of the cells- belonging to the lam. mult, (indusium). As we pass towards QQ' , in the area PP'~QQ' , all the cortical layers appear and increase in thickness. The area Q^}'RR' contains the knee of the frontal cortex and the line IX-IX' runs through the very tip of the frontal pole.
The area RR'-SS' is similar in cell-lamination to the area AA'-BB' in the sagittal section (fig. 2) and the area KK'-LU (fig. 4), and needs no explanation. At RR' the two sublayers of the lam. mult, as seen towards SS' , fuse into one.
In the area SS'-TT', as in the area LL'-MM' (fig. 4), the lam. grar. int. increases markedly in thickness and cell-density, the lam. gang, at the same time becoming thinner.
In the area TT'-UV , the total thickness of the cortex decreases. Every layer takes part in this thinning and the cell arrangement in every layer loses little by little its regularity. Speaking broadly, the area TT'-UU' has a structure different from that of SS'-TT', in that the lam. gran. int. becomes so thin that it is difficult to recognize it, even in material fixed in formol. Though the lam. mult, in this area does not sho w the pale band separating it into two sublayers, yet we can distinguish the two sublayers, the ectal or subganglional sublayer consisting of inflated cells and the ental, narrow band consisting of several rows of the somewhat larger, polymorphous cells, more deeply stained.
The area UU'~WW' hasla modified structure. The fissure rhinalis, denoted by V, lies midway in this area. Between the fissura rhinalis and the cornu Ammonis, there is a light band free from cells in the place of the lam. gran, int., although, near the fissura rhinalis, this layer has a small number of more or less scattered cells. The lam. pyr. shows distinctly two sublayers, the ectal or subzonal one consisting of a band of the largesized, deeply-stained, crowded pyramids, and the other ental sublayer of a band of somewhat lightly stained, smaller-sized, inflated cells, which are less crowded than in the subzonal sublayer. This ental sublayer occupies about two-thirds of the thickness of the entire lam. pyr. The lam. gang, is scarcely to be distinguished and the lam. mult, is here formed by a single layer and is also thin. I would like to call attention here to the fact that though the large-sized, deeply-stained pyramids lying subzonally in the area UU'-WW are usually held to be derived from the cells of the lam. pyr. by change of form, I am much inclined to attribute these cells to another source, but the discussion of this question must be reserved for another paper.
The area WW'-X' shows a cell-lamination, which is very • peculiar in that the subzonal sublayer of the lam. pyr. suddenly increases in thickness, the pyramids become crowded, and the ental, epigranular sublayer becomes so thin as to be almost indistinguishable. The light cell-free band corresponding to the lam. gran. int. widens here.
At X' the lam. pyr. ceases abruptly. In the area X'-YY', the cell-free parts of the cortex becomes much thickened, the laminae pyr. et gran. int. disappear entirely and the remainder of the lam. gang, undergoes a sudden thickening and becomes characterized by large-sized pyramids well dispersed. The lam. mult, also disappears at YY', giving place to the pyramids of the lam. gang., which continues into the cell band of the cornu Ammonis beyond YY'. The area X'-YY' is the same part of the brain as that represented in the area EE'-FF' of figure 2, namely the subiculum cornu Ammonis.
Figure 6 shows also the positions of the five localities at which the thickness of the cortex was measured on the horizontal section.
Locality IX. The line IX-IX' has been measured through the tip of the frontal pole along: the line of the cell radiation. This measurement corresponds nearly to that at /-/' in the sagittal section but lies a little nearer the median plane. Here the lam. pyr. occupies about one-fifth of the total thickness, the lam. gran, int. is thin, while the lam. gang, as well as the lam. mult, are thick, the latter being represented here by one layer.
Locality X. The line X-X' has been measured at the middle of the area SS'-TT'. The line X-X' was determined by joining the point midway between the frontal border of the cornu Ammonis and the tip of the cortex at PP', with the lateral cortex by a line perpendicular to its ectal surface. In this part, just as in the corresponding area LL'~MM' in figure 4, the lam. gran, int. increases its thickness considerably.
Locality XL This has been measured, like locality III, at the level of the forepart of the cornu Ammonis where the cerebral cortex is becoming gradually thinner.
Locahty XIII. Near the occipital pole of the hemisphere, this line XIII-XIII' has been measured at the latero-caudal point where the cerebellum and the occipital lobe come into contact. * This locahty is situated between V and WW and here the light cell-free band, corresponding to the position of the lam. gran, int., is clearly marked.
Locality XII. This locality has been measured about midway between localities XI and XIII, near the fissura rhinalis {V). This corresponds roughly to the locahty VIII in the frontal section. For convenience of comparison I averaged the five measurements here described and this value is named the average thickness of the cerebral cortex in the horizontal section." "
The measurements at localities IX-X-XI-XII-XIII in the horizontal section, like those at localities I-II-III-IV-V in the sagittal section, both reveal a gradual decrease in the thickness of the cortex from the frontal to the occipital pole. By the thickness at IX and X the development of the frontal cortex, by the thickness at XI the development of the temporal cortex, and by the thickness at XII and XIII the development of the occipital cortex can be judged.
V. Notes on the Cortex of the Newborn Albino Rat Brain
In the foregoing chapter I have given a general description of the lamination of the mature cerebral cortex of the albino rat. But, in the case of the younger animals, especially at birth, the appearance of the sections is, of course, not the same, since the cortex is in an earlier stage of development. Figure 7 shows a general picture of the sagittal section of the newborn rat brain
Fig. 7 Diagram showing the cortical cell-lamination of' the newborn albino rat brain, which weighs 0.2 gram. Crosses (X-X) show the location from which figure 8 was taken.
(based on Rat. No. II a, brain weight 0.2132 grams), and figure 8 shows an enlarged, diagrammatic picture of the cell-lamination from the part marked with two crosses in figure 7, corresponding to locality II (fig. 2). In comparison with figure 9, which shows the corresponding part of the cerebral cortex in the sagittal section of the mature rat brain, locality II (fig. 2), the newborn cortex presents an appearance of more complexity, especially in the regions adjoining to the ventricular walls. The cells which
538
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GROWTH OF THE CEREBRAL CORTEX 539
are becoming ganglion cells have originated from the germinal cells lying in the ventricular wall and have migrated from there to their final position in the cortex. In the rat brain, cell migration is yet in progress at birth, giving the sections a peculiar aspect. The complication of the cortical lamination in the newborn rat is due to the' existence of one or two transitional layers (so-called 'Uebergangsschichten', fig. 8, Tr.) between the germinal cells (fig. 8, G) in the ventricular wall and the cortex proper. These transitional layers are no more to be seen in the brain weighing more than 0.5 grams (age about 5 days).
On examining figures 7 and 8 it is seen that the five cortical layers are not yet clearly distinguished. The lam. zon. (fig. 8, /) is fairly thick and the borderline between this layer and the underlying lam. pyr. (Ill) does not run smoothly as in the adult, but shows a fine zigzag, suggesting that the invasion of the zonal region by the pyramids is still going on. The pyramids are not yet in a mature condition, their protoplasm is scanty and homogeneously stained and their form somewhat spindle-shaped. The nuclei stain less deeply than in the adult brain and the chromatin is not completely visible. The lam. gran. int. cannot be distinguished. The position of the lam. gang. (V) is already sparsely occupied by large-sized pyramids rich in protoplasm, but mixed up with them is a large number of small-sized pyramids, some of which are growing to be ganglion cells and some, probably, on their way to the lam. pyr. The lam. mult. (VI) is divided into two sublayers by a band, poor in cells, as is seen in the adult (fig. 9), but at this phase the number of the ceUs in the ental sublayer is very much greater and they are larger and better stained than the cells in the ectal sublayer. Their orientation is irregu Fig. 8 Diagram of cell-lamination of the prematurely-born albino rat brain weighing 0.2 gram, schematically enlarged from the designated part (X-X) of figure 7. /, lamina zonalis; III, lamina pyramidalis;'F, lamina ganglionaris; VI, lamina multiformis; Tr., transitional layers; G, germinal layer or matrix at the ventricular wall. Magnification X 100.
Fig. 9 Diagram of cell lamination of the adult albino rat brain weighing 1.8 grams, schematically enlarged from the locality II, figure 2, and corresponding to that selected for figure 8. /, lamina zonalis; //, lamina pyramidalis; ///, lamina granularis interna; V, lamina ganglionaris; VI, lamina multiformis. Magnification X 65.
540 NAOKI SUGITA
lar, some having the apical process vertical, some oblique and some in an inverted direction (Hatai '02). This arrangement indicates possibly that this sublayer serves as a secondary station for the migrating neuroblasts, where immature cells in part mature and orient themselves, though most of them must have finished their rotation while passing through the transitional layers. But we cannot regard this sublayer as purely temporary, for it remains all through life persisting as a special thin layer containing large, polymorphous, deeply-staining cells, that is the ental sublayer of the lam. mult. However, in this earlier phase it contains transitional elements, since the number of cells is greater here in younger than in the older brains, so that in the newborn we see even seven or more rows of cells in this sublayer, while in the adult only three or four rows appear. The ectal sublayer of the lam. mult, has already in it polymorphous cells destined to become ganglion cells. These are round, somewhat larger than the pyramids in the lam. pyr., their apical processes all directed ectad. In this layer a relatively large number of small, round cells, probably future glia cells, are also to be seen, while we do not see as yet cells of this type in the more ectal layers.
In the newborn brain, there are one or in some earlier born, two transitional layers between the lam. mult, and the ventricular wall. At the earlier stage before birth there are always two such layers (fig. 8, Tr.), afterwards but one, the ental layer having disappeared. At birth, the wall of the ventricles consists of germinal and indifferent cells, among which are many mitotic figures. The thick layer of these crowded cells is the starting place of the newly divided cells on their migration, during which they rotate through 180° as they pass through the temporary layers to their final station in the cortex. During the earlier stages and when mitosis is most active (Allen '12), the neuroblasts are densely crowded both in the transitional layers and at the cortex. The cells, crowded in the ventricular wall are small in size, have deeply-staining nuclei and scanty protoplasm. These cells poor in protoplasm form chains which fuse into a
GROWTH OF THE CEREBRAL CORTEX 541
loose network, but always show the general direction of the current of migration.
The (one or two) transitional layers lie between the ental sublayer of the lam. mult, and the ventricular wall, separated by pale bands which in turn are bridged by slender chains of cells. These transitional layers are probably the loci where the indifferent cells or neuroblasts perform their rotation. The cells of the transitional layers have small nuclei and more or less rich protoplasm and their arrangement suggests every stage of rotation. In brains a few days before birth (brain weight, 0.15 to 0.17 gram) this layer is clearly divided into two layers by a light band, as seen in figure 8, but in older brains the ental layer diminishes, or may even disappear leaving a single layer. The relatively broad layer poor in cells lying between this layer and the ventricular wall is prettily striped by the chains of the migrating cells which run radially at wide intervals. The light band lying between the transitional layers and the ental sublayer of the lam. mult, is narrow. In contrast to the small cells in the transitional layers, the cells of the lam. mult, are large and better stained.
In the newborn brain these transitional layers can be seen always lying between the ventricular wall and the cortical layers proper, so that in the sagittal sections they extend from the frontal tip where the cerebral cortex goes into the olfactory bulb, to the beginning of the cornu Ammonis. In frontal and horizontal sections, those transitional layers are also seen where the ventricular wall is close to the cerebral cortex. Where the cortex overlies interbrain structures, the transitional cell layers are not distinct.
These transitional layers disappear three or four days after birth and are not to be seen any more in brains of over 0.5 gram, in which the indifferent cells or neuroblasts radiate in loose chains from the ventricular wall directly to the ental sublayer of the lam. mult., without forming distinct transitional layers. The cells making the chains are less crowded and majority of them small-sized as seen in the younger brains.
542 NAOKI SUGITA
During the first week after birth, .when the increase of the cortex in thickness is most energetic, cortical cell-lamination is almost completed. Thus, at the fourth day after birth a light band appears between the ]am. pyr. and the lam. gang., which suggests that the differentiation of the latter is now at an end. The ganglion cells are then in five or more rows. At birth, the ental sublayer of the lam. mult, has seven or more rows of multiform cells, but these decrease with advancing age and by the eighth day they have been reduced to four rows of cells or less. I will reserve the details of these changes till I take up in a later paper the development of each type of ganglion cell according to age.
According to His ('04) the transitional layers of the cerebral cortex may be recognized in the human embryo at 4 months, and, according to Melius ('12) they are still visible in the brain of an eight months foetus and also of a newborn (stillborn) child. Anyhow, the fact that they are not so distinctly visible in a newborn human child as in a newborn rat, and that they persist till after birth in the latter brain, shows, as already stated by Donaldson ('08), that the albino rat is born with a brain somewhat less mature than that of the human child.
The transitional layers have not been subjected to measurement, because they do not belong to the cerebral cortex proper, and in making the measurements care has been taken to exclude the transitional layers in the very young brains.
VI. THE CELL-LAMINATION OF THE CORTEX OF THE ALBINO RAT
In previous chapters (figs. 2, 4, and 6), I have described the laminar structure of the cortex of the albino rat, as far as the cortex is presented to view in my sections. A description of the cortical lamination of the entire hemisphere is not included in the plan of this study, but, as there has been no description previously published on the cortical lamination of the albino rat, it has seemed worth while to refer here to some papers on the cortical celllamination in the Norway rat, from which the Albino has been derived, and in some other mammals more or less closely related and to compare the present observations with those previously made.
GROWTH OF THE CEREBRAL CORTEX ^43
The first author to study the cell-lamination of the cerebral cortex of the rodents was Bevan Lewis ('81). He took the rabbit and the Norway rat together as the representatives of the rodents, but gave the details for the rabbit brain only, recording for it the thickness of the cortex and of size of the cortical cells. Bevan Lewis found cell-lamination in the cortex of the rabbit similar to that in the rat, so I will here cite his types of the celllamination for the rabbit only.
He divided the entire cortex of the hemisphere into eight areas distinguished by the laminar structure.
1. Type of upper limbic arc.
2. Modified upper limbic type. .3. Outer olfactory type.
4. Inner olfactory type. \ Comprised within the limits of the lower and
5. Modified olfactory type./ anterior limbic arcs.
6. Extra-limbic type.
7. Type of cornu Ammonis.
8. Type of olfactory bulb.
Figure 10 reproduces the figures given by Lewis to show the distribution of these types of cortical structure. So far as these areas occur in my sections, a comparison of the lamination of the cortex of the albino rat with that of the rabbit shows the two cortices to be similar. It, however, seems hardly necessary to record the details of the comparison on this occasion, although such a detailed comparison has been made by me. According to Lewis the parietal cortex of the rabbit has a thickness of 2.8 mm.' while at the corresponding locality (Locality VII shown in figure 4) the cortex of the rat brain is 2.2 mm. thick (corrected value) . From this, it would appear that the rabbit has a thicker cortex, but systematic investigations would be required to really determine this point.
Recently Fortuyn ('14) has studied thoroughly the laminar structure of the cortex in several rodents. He examined nine
1 Measured on the section which was cut by the freezing microtome from the fresh material and then hardened by osmic acid, stained by aniline black and mounted in Canada balsam. According to his statement, we obtain, by this method, the natural depth of the cortex, no shrinking occurring if the preparations have been carefully made (Lewis, '78).
544
NAOKI SUGITA
species and among these was Mus decumanus (Pall), or Mus norvegicus (Erx.), that is, the Norway rat, the wild form from which the Albino has been derived. He has divided the entire hemispherical surface into twenty-seven areas according to the characteristics of the laminar structure and these are
\W*\ Upper limbic type.
WM\ Modified upper limbic type.
^^ Modified olfactory type.
^^ Outer olfactory type.
^B Inner olfactory type.
I I Extra-limbic type.
Fig. 10 Cortical areas of rodent's hemisphere' — rabbit— reproduced from the original by Bevan Lewis.
shown in figure 11 copied from his paper. In figure 11, I have designated with FF, SS and HH the levels at which my sections were taken ; FF, SS and HH being the abbreviations respectively of the frontal, the sagittal and the horizontal sections.
The following table is from Fortuyn's description of the cortical ceU-lamination of the Norway rat brain. Under the letters desig
GROWTH OF THE CEREBRAL CORTEX
545
s —
P'ig. 11 Cortical areas of Mus decumanus (Pall), slightly modified from the original by Dr. Fortuyn; the characteristics of each area designated on the map are described in text. FF, SS, and HH show respectively the levels from which the sagittal, frontal and the horizontal sections were taken for my present studies.
THE .lOrnXAI. OF COMPARATIVE NEUROLOGY, VOL. 2S, NO. 3
546
NAOKI SUGITA
Dating the areas shown in the maps, the layers are given by Roman numbers, that is; I. means the lamina zonalis, II. means the lamina granulans externa, which is not distinguishable in the rat brain, III. means the lamina pyramidalis, IV. means the lamina granulans interna, V. means the lamina gangUonaris and VI. means the lamina multiformis. In several areas, some af these Roman numbers are absent, implying that in these areas the corresponding layers are not distinguishable or are lacking. Mathematical symbols, as = or +, show the relations of the thickness of each layer. Pyr. means pyramidal cells. If the cell form is not specially given, it is assumed to be polymorphous. The general characteristics of the lamination of the area are indicated in brackets and some characteristics of the individual layers are indicated by a word or two after the Roman number. The absence of remark indicates the ordinary arrangement of a layer.
Area a.
IV.
= very narrow.
I. .
V.
= broader than III + IV;
V. typical Pyr. Area a', (compact structure).
I
III. = narrow; Pyr. crowded.
VI. Area f.
many Pyr. divided into two sublayers
by a light band, (radiating; otherwise similar
IV.
V.
VI.
Area a".
Pyr. = V.
I. III. IV.
to area f).
I.
V.
VI.
= 1 X VI; Pyr.
V. VI.
elongated Pyr. not divided into two • sublayers.
Area c.
I.
III.
IV.
Area g.
(bottom of the fissura rhi
= narrow.
= narrower than III.
T
nalis at frontal part; not shown in figure 11).
V.
VI.
Area d.
I.
III.
V.
= III + IV; Pyr.
= i X V.
(radiating and agranular).
Pyr. Pyr.
III. Pyr. resembling granules.
IV. not numerous. V. Pyr.
VI
Area h + h".
VI.
I.
Area f. I.
III. IV.
Pyr. crowded together, few cells scattered.
III.
= narrow; typical Pyr.
VI.
GROWTH OF THE CEREBRAL CORTEX
547
Area h'.
I
IIIA. = narrow; large Pyr. IIIB. = broad; small Pyr. IV. = narrow; poor in cells. V. = narrow; few Pyr., indistinct. VI. many cells. Area j .
I
III. = 2 X IV; Pyr.
IV. clouded. V. Pyr.
VI. Similar to VI of area f, divided into two sublayers. Area k.
I
III. Pyr.
IV. = narrower than III; less
granules than in area j. V. = III + IV; small typical
Pyr. VI. = narrow. Claustrum. Area k".
I
III. = narrower than III in area
k.
IV. very few cells, light band. V. = narrower than V in area k.
VI. = narrower than VI in area k. Claustrum. Area 1. (compactly constructed, situated at bottom of the fissura rhinalis near h'; not shown in figure 11).
I
IV
V. = narrow. VI. = narrow. Area m'. (radiating). I
III. = rather narrow; Pyr.
IV. = narrow; poor in cells.
V. = broad; Pyr; rather poor in
cells. VI. very small cells.
Area n.
I
Ill
IV. granular density great. V. many largest Pyr.
VI
Area o. (free from cortex). Area p.
I
Ill
IV. = narrow; few cells. V. Pyr. VI. nor divided by a light band, but close to the white substance a narrow layer of spindle-shaped cells. Area r. (fascia den tata).
I
IV. = narrow; cells crowded together, beneath IV some scattered cells. Area s. (cornu Ammonis).
I
V. Pyr. dispersed. Area w.
I
III. typical Pyr.
IV. rich in cells, distinct. V. small typical Pyr.
VI
Area x.
I
IIIA. Pyr.
IIIB. = I X IIIA; Pyr. IV. no cells, light band.
VI
Area z. (agranular, light bands between III and V, and also between V and VI) .
I
111. typical Pyr. V. Pyr.
VI
Area z".
I
IV
V. = IV; Pyr. VI. = narrow.
548 NAOKI SUGITA
Areaz'". Area aa.
I I
III. = narrow; Pyr. crowded. III. = ^ X III of area z'".
IV. =2 X III; colls closer IV. = | X IV of area z'".
crowded near III. V. = broad; IPyr.
V. = 2 X (III + IV); cells dis- VI
persed. VI. = V.
The areas appearing in my sections are collated below, with the corresponding areas from Fortuyn's map. The laminar structure was found generally similar to that described by Fortuyn.
Sagittal sections {fig. 2) Fortuyn's map
Area AA'-BB' f andf
Area BB'-CC j or n
Area CC'-DD' w
Area DD'-EE' not precisely described, probably o?
Area EE'-FF' .\s'?
Frontal sections {fig. 4)
Area GG'-HH' c
Area HH'-KK' f
Area KK'-LL' f
Area LL'-MM' j
Area MM'-OO' k
Area 00' h + h"
Horizontal sections {fig. 6)
Area PP'-QQ' c
Area QQ'-RR' f '
Area RR'-SS' f
Area SS'-TT' j
Area TT'-UU' p
Area UU'-VV .w
Area VV'-WW h'
Area WW'-XX' not precisely described, probably o?
Area XX'-YY' " s'?
Thus we see that the description by Fortuyn of the cortex of the Norway rat is in the main applicable to the albino rat. This is, of course, what we should expect. However, there appear to be some slight differences shown by the areas VV'-WW, WW
GEOWTH OF THE CEREBRAL CORTEX 549
X', X'~YY', DD'-EE' and DD'~FF' in my sections. All of these areas lie near to the cornu Ammonis and show a structure somewhat different from that described by Fortuyn. But, fortunately, none of these areas include localities where measurements of the cortex were made, so that the questions thus raised may be reserved for discussion in another paper.
In addition to the authors just cited, Brodmann ('09), in his valuable work on the cortical localisation of function in ijiammals, has examined the localisation in the cerebral cortex of the rabbit (Lepus cuniculus) and of the spermophilus citellus, as the representatives of the rodents. Though his description of the rabbit cortex does not extend to the details of the structure of the cell layers and for this reason, his 'Hirnkarte' can not be precisely compared with my sections in respect to the laminar structure, yet I think his diagrams do not deviate much from Fortuyn 's map. For the sake of completeness, therefore, I give a table collating his regional terms with the areas mapped by Fortuyn and also with the corresponding areas shown in my own sections.
Brodmanii's term, (anatomico-physiological) Fortuyn My section^!
Regio praecentralis f, f Areas AA'-BB', HH'-KK', KK' LL', QQ'~RR'.
Regio parietalis j, n Areas BB'-CC, LL'-MM', SS' TT'.
Regio occipitalis w Areas CC'-DD', UU'-VV.
Regio insularis k Area MM'-OO'.
Regio temporalis p, x Area TT'-UU'.
Regio cingularis c Areas GG'-HH', PP'-QQ'.
Regio retrosplenialis z, z", z'".. .No section.
Regio hippocainpica r', s.
Regio olfactoria h + h" Area 00' .
VII. THE THICKNESS OF THE CEREBRAL CORTEX ACCORDING TO BRAIN WEIGHT— TABLES AND CHARTS
A. Direct measurements on the slide
In the first instance, the thickness of the cortex was measured at localities I-XIII inclusive, on the sections as prepared and recorded without any corrections.
550
NAOKI SUGITA
The results are condensed in table 5, where the average thickness for the sections in each plane is given and also the general average for the three sections is combined, the arrangement of the data being according to brain weight groups.
Chart 1 repeats in graphic form the data in table 5.
TABLE 5
Showing the general average thickness of the cerebral cortex of the albino ral according to brain weight groups, also the average thickness in the sagittal, the frontal and the horizontal sections
SAGITTAL SECTION
FRONTAL SECTION
HORIZONT.VL SECTION
GENERAL
AVERAGE
BBAIN
WEIGHT GKOUP
Number
of
cases
Brain weight
Thickness
Thickness
Number of
cases
Brain weight
Thickness
Brain weight ,
Thickness
grams
TJiTn.
mm.
fframs
mm.
grams
mm.
I
3
0.161
0.47
0.51
II
5
0.251
0.58
0.65
2
0.292
0.70
0.265
0.64
III
5
0.358
0.83
0.90
3
0.317
0.74
0.344
0.85
IV
6
0.432
0.93
1.00
3
0.419
0.90
0.428
0.94
■ v
9
0.542
1.06
1.18
5
0.546
1.05
0.543
1.10
VI
3
0.639
1.16
1.30
2
0.631
1.14
0.636
1.20
VII
2
0.750
1.30
1.43
2
0.761
1.26
0.754
1.33
VIII
6
0.841
1.32
1.47
4
0.848
1.23
0.843
1.34
IX
3
0.964
1.36
1.53
2
0.939
1.35
0.956
1.41
X
3
1.040
1.31
1.51
3
1.054
1.37
1.045
1.40
XI
4
1.171
1.40
1.53
1
1.121
1.49
1.154
1.47
XII
2
1.253
1.43
1.55
3
1.240
1.44
1.249
1.47
XIII
5
1.335
1.39
1.52
3
1.351
1.39
1.340
1.43
XIV
3
1.445
1.40
1.51
2
1.455
1.48
1.448
1.47
XV
o
1.554
1.44
1.50
2
1.566
1.48
1.558
1.47
XVI
4
1.656
1.42
1.46
4
1.678
1.51
1.663
1.46
XVII
4
1.726
1.47
1.51
2
1.730
1.42
1.727
1.47
XVIII
3
1.839
1.52
1.52
2
1.823
1.54
1.833
1.53
XIX
1
1.924
1.44
1.50
XX
2
2.054
1.53
1.47
1
2.004
1.69
2.037
1.56
The methods used in making the measurements have been described already. In applying these methods, from 2 to 12 measurements were made in each locality of each brain and the average of these recorded as the observed value. These data for each locality, in each brain of a brain weight group, were then averaged and the value obtained taken as that for the
GROWTH OF THE CEREBRAL CORTEX
551
group. The average measurements for each locality in each plane (section) were then again averaged to give the average thickness of the cortex in the sagittal, frontal and horizontal sections of each brain weight group. In chart 1, these are the values used for the ordinates, the average brain weight of the group being entered on the abscissa.
.
'Jiji^
~.^
-,;>
i-'r^
^*^
'^z-~
—A
--F
'-^
^
-r~
■•-'-'
.
'■
<<-■ '
y^.f
£
^'
/^
//'•
-;
1
1
1
01 Q2 Q5 04 OS 06 Q7
09 10 11 n 1-3 J4 15 16 17 i.8 19 20
Chart 1 Giving the thickness of the cortex on slide (not corrected) in sagittal, frontal and horizontal sections and the general average thickness, according to brain weight. Based on table 5. • — • — • — S Average thickness of the cortex in
sagittal section, measured on slide. F Average thickness of the cortex
in frontal section, measured on slide. H Average thickness of the
cortex in horizontal section, measured on slide. • "A General average
thickness of the cortex of three kinds of sections, measured on slide.
All these data have been tabulated in detail and are on file at The Wistar Institute together with the sections used. The full tables have not been printed here because it is evident that the observations are open to a correction. The sections are from brains that have been subjected to an elaborate technique, while the brain weights are from the fresh specimens, and what we should like to know is the thickness of the cortex in the fresh brain. This can be obtained only by applying a correction to the observed values.
552 NAOKI SUGITA
B. Measurements corrected for the effects of technique
The figures given in the foregoing table 5 and chart 1 were based on the direct measurement of sections prepared by the uniform technique as explained in a former chapter. But, since the shape and volume of the brain suffer some passive changes during preparation for study in this way, the values obtained by measurement on the shde do not represent those for the cortex in the fresh condition. We might think of these modified measurements as comparable among themselves, but, as will appear later, even that is not the case, since the change shown by a brain is related to its age (or size) .
Thus, during fixation in the Bouin's fluid, the younger brains are little influenced in size, but, the more the age advances, the more the fluid causes shrinkage during fixation in all dimensions, especially in the sagittal direction. During fixation and dehydration, while the brain is passing through the several grades of alcohol, the older brain has more substance extracted by alcohol than younger. As a matter of routine I took the total weight of brain, just before it was transferred from 90 per cent into the absolute alcohol. In younger brains the weight is reduced to ca. 80 per cent of the fresh weight, while older brains, for example, that of a rat 150 days old or more, are reduced in weight to 66 per cent of the fresh weight.- Accordingly, of course, the size of the total brain suffers more shrinkage, as the age advances, during the process of dehydration.
It follows from this that the younger brain should have a relatively thicker and the older brain a relatively thinner cortex on the slide, as a result of the foregoing treatment. It is a question whether the white and the gray substance respond in exactly the same manner, but for the moment we assume that they do.. Measurements indicate, however, that the shrinkage of fibers along their length is larger than that along their transverse direction, but the difference is so small that it may be neglected.
'^ Correction was not made for the weight lost by the replacement of water by alcohol. Details on this point will appear in a later part of this series of studies.
GROWTH OF THE CEREBRAL CORTEX 553
In two brains of the same age and treated by the same method, the ratio between any diameter measured on the fresh brain and that measured after imbedding in paraffine is ahnost constant, although heavier brains suffer shghtly more shrinkage. But the ratio between a gi^'en diameter on slide and the same diameter in paraffine block has proved less constant, probably because, as mentioned earlier, on extending or unfolding the sections on slides the results are modified by slight differences in the temperature applied or in the duration of heating. I could not avoid this irregularity, though I endeavored to do so. These minor effects of the technique might be ignored in case of purely histological or pathological investigations, which aim only to detect changes in the formal aspects of the elements of tissue and do not regard the minute changes in size caused by the technique; but in the present study which requires painstaking exactness at every point, some effort must be made to correct for these changes.
At the beginning of this study, it was appreciated that such changes would occur, and the necessary preliminary observations were made (Sugita, '17). On the fresh rat brain I measured in each case the following diameters to 0.05 mm. by placing the brain on the glass-plate, basal surface down. Figure 12 gives the position of these diameters.
1. Width AB, (W.B,) the greatest width along the frontal plane.
2. Width CD, (W.D), passing through the middle point of the fissura sagittalis and parallel to AB. This corresponds to the plane in which the frontal sections were taken.
3. Length EF, (L.F), passing through the frontal pole and running parallel to the mesial surface of the hemisphere. This corresponds to the plane of the sagittal sections.
4. Length EG, (L.G), passing from the frontal pole at E to the occipital pole at G. This measurement gives the greatest length.
5. Height HK, {Ht), (fig. 12 b) from the stalk of the hypophysis to the dorsal surface and vertical to the basal surface of the brain.
554
NAOKI SUGITA
The results of the measurement are given in chart 2. This chart shows the curve of each measured diameter in milhmeters given on the ordinates, the brain weight being entered on the abscissa. Generally considered, at birth, the width W.B surpasses the length L.G, but after the third week, the length increases more rapidly and finally surpasses the width at the end of the seventh week, when the hemispheres appear somewhat elongated and ovoid.
Among these diameters, L.F is in the plane from which the sagittal sections were taken and W.D in the plane from which the
a g
Fig. 12 a. Dorsal view of the albino rat brain weighing 1.5 grams, enlarged 1.8 diameters. To show the positions at which the two measurements for the width and the two measurements for the length were taken. AB = Width W.B, CD = Width W.D, EF = Length L.F and EG = Length L.G.
b. Lateral view of the albino rat brain weighing 1.5 grams. Enlarged 1.8 diameters.- To show the position at which the height was measured. HK = Height Ht.
frontal sections were taken. So I have used these values as those from which to obtain a coefficient for correction.
Assuming that, by fixation and when unfolded by heat on slides, the section shrinks or extends uniformly, and, that the white and the gray substancss suffer approximately the same shrinkage or extension as the result of the treatment, I have selected the following correction-coefficients for use in this series.
In the sagittal section, the thickness of the cortex measured on the sfide being represented by Ts and the thickness of the fresh cortex by Tp. Then
L.F (fresh)
Tb X
L.F (on slide)
(1)
GROWTH OF THE CEREBRAL CORTEX
555
1 1
^L
G
B
F
^tr-^
,o-
_o
\-^
k"
/;,
.-»•■"
^
~y
... w
D
>rAd
■*'■
—..-■'
—'
—
--t^* ■ ^^^
.«-— ^
X
^y-i'
i 1
X.
'■■y
zA'
, Hi
n
/yV
,o--"
.,
"■'
,.*_—
"""
xy/y
^,
—
-.
^
~ 1
/
■■'V
/ .
„^"^
^ '
V
/ ,
■
,.-'
•'■
'-'
/
-^'
1
4
0.1 Q2 03 0.4 0.5 05 QT 08 09 I.O 11 12 13 14 1.5 lb 17 18 19 20
Chart 2 Giving for each brain weight group, in millimeters, on brain weight in grams, the values for the several diameters. W. B. and W. D., width; L. F. and
L. G., length; Ht., height. • • = W. B. • • = IF. D. O O = L. G.
O 0=L.F. X X = Ht.
where EF is the longitudinal diameter in the plane of the sagittal section (fig. 12). The thickness of the cortex at localities I-V was corrected by the use of this coefficient.
For the frontal section the corresponding formula is
n = Ts X
W.D (freshj W.D (on slide)
(2)
where CD is the width in the plane of the frontal section (fig. 12). The thickness of the cortex at localities VI, VII, and VIII was corrected by the use of this coefficient. Of course, the actual measurement on the slide was in this section that of one hemisphere only. The observed value obtained was therefore doubled for use in the formula.
After considering several possibilities, I decided to use for horizontal sections, the value for the maximum width of the brain, AB, in order to obtain the necessary formula. Thus,
556 NAOKI SUGITA
r - T -V W'.-B (fresh)
W ./> (on slide) ^
where AB is the greatest width of the brain (fig. 12). The thickness of the cortex, at locaUties IX-XIII was corrected by the use of this coefficient.
Mil. CORRECTED DATA PRESENTED IX TABLES AND CHARTS
Tables 6, 7 and 8 show the corrected values of the cortical thickness at the thirteen locaHties in the three kinds of sections examined. The data for the coefficients employed in correcting the individual entries are given separately together with the coefficients for each brain weight group. The method of applying the coefficients has already been described. The average thickness of the cortex for each brain was obtained from the corrected individual measurements. Charts 3 to 8 are based on the foregoing tables, charts 3, 5 and 7 showing the individual measurements and charts 4, 6 and 8 the average \'alues of each locality for each brain weight group, in sagittal, frontal and horizontal sections respectively.
In tables 6, 7 and 8, the endeavor has been made to introduce all the details necessary for the interpretation and control of the results. In table 6, for example, the entry III a, age 2 days (see also table 1), is for a rat having a brain weight of 0.3105 g.-ams. For the correction of the observed cortical thiclvness in the sagittal section, the coefficient was found by formula (1) page 554. This correction coefficient was applied to the measurements, as made on the slide, for each of the localities I to V at which the thickness of the cortex in the sagittal section had been determined. For each locality the corrected measurement in millimeters is given in the table and at the end of the line the average of the five corrected values appears.
Similarly by using the correction coefficient determined by formula (2) correction has been made in a like manner for the direct measurements at the three localities VI-VIII in the frontal section, table 7, taken from the other hemisphere of the brain, one hemisphere of which had been used for the sagittal section.
GROWTH OF THE CEREBRAL CORTEX
557
TABLE 6
Showing the corrected values of the cortical thickness in the sagittal section for each individual and for each brain weight group. The data for the coefficients are indicated separately for each brain and the coefficient is given explicitly in the average for each group. Group averages in italic
COEFFICIENT
THICKNESS OF
THE CORTEX (s.^GITTAL SECTION)
BR.\IN WEIGHT GROUP
BRAIX WEIGHT
Diam.
L.F
on fresh
brain
Diam.
L.F
on slide
Loc.
I
Loc. II
Loc.
Ill
Loc. IV
Loc. V
Average
grams
mm.
m m .
m m .
til nt ■
m m .
mm.
mm.
»/; 7/1 .
I a
0.153
5.50
4.97
0.59
0.54
0.49
0.41
0.35
0.48
c
0.154
5,60
4.80
0.73
0.64
0.55
0.44
0.35
0.54
b
0.177
5.70
5.13
0.71
0.67
0.55
0.45
0.39
0.55
0.161
1.1
S
0.68
0.62
0.53
0.43
0.36
0.52
II a
0.213
5.80
5 13
0.77
0.73
0.60
0.51
0.46
0.61
b
0.221
6.00
5.43
0.71
0.66
0.56
0.48
0.36
0.55
c
0.261
6.60
5.52
0.92
0.86
0.80
0.73
0.72
0.81
d
0.271
6.75
5.80
0.93
0.82
0.70
0.67
0.45
0.69
e
0.288
6.70
6.11
0.91
0.76
0.68
0.52
0.41
0.66
(Birth)
0.251
1
(4
0.85
0.77
0.67
0.56
0.48
0.67
III a
0.311
7.35
6.55
1.01
0.99
0.89
0.74
0.56
0.84
b
0.322
7.20
6.26
1.22
1.04
0.86
0.68
0.50
0.86
g
0.374
7.40
7.65
1.18
1.01
0.89
0.77
0,57
0.88
c
0.390
7.50
6.75
1.24
1.03
0.88
0.73
0.63
0.90
i
0.395
7.95
7.20
1 41
1.08
1.01
0.81
0.65
0.99
(2 days)
0.S58
/.
09
1.21
1.03
0.91
0.75
0.58
0.90
IV b
0.400
7.70
6.65
1.30
1.14
1.01
74
0.65
0.97
a
0.402
7.75
7.65
1
24
1.05
0.92
0.71
0.57
0.90
c
0.420
7.95
7.40
1
27
1.14
0.92
0.73
0.58
0.93
i
0.443
8.30
8.00
1
48
1.22
1.10
0.82
0.64
1.05
d
0.459
8.05
7.60
1
34
1.14
1.00
0.77
0.61
0.97
e
0.466
8.40
8.30
1
39
1,23
1 10
0,94
0.79
1.09
(4 days)
O.Jf32
1.
06
/
34
1.15
1.01
0.79
0.64
0.99
V i
0.501
8.35
7.90
1.49
1,31
1.13
0,91
0.72
1.11
a
0.525
8.55
8.30
1.48
1,24
0.99
0,76
0.64
1.02
b
0.528
8.50
8.05
1.57
1 31
1.13
0.89
0.67
1.11
c
0.534
8.65
7.70
1.48
1.24
1.10
0.92
0.74
1.10
d
0.537
8.30
7.70
1.50
1 30
1.16
0,89
0.73
1.12
e
0.555
9.25
8.50
1.60
1.49
1,39
1.05
0.74
1.25
f
0.558
9.20
S.60
1.66
1 36
1,20
0.94
0.75
1 18
g
0.564
8.85
8.50
1.51
1.30
1,14
90
0.74
1.13
h
0.579
9.10
8.25
1.64
1.40
1.24
96
0.73
1 19
(6 days)
0.542
1
07
1.55
1.33
1.16
0.92
0.72
114
TABLE 6— Continued
BRAIN WEIGHT
COEFFICIENT
THICKNESS OF
THE CORTEX (SAGITTAL SECTION)
BRAIN WEIGHT GROUP
Diam.
L.F
on fresh
brain
Diam.
L.F
on slide
Loc.
I
Loc. II
Loc.
Ill
Loc. IV
Loc. V
Average
grams
mm.
mm.
m,m.
mm.
mm.
mm.
mm.
■nim,.
VI c
0.610
9.35
8.25
1.79
1.42
1.37
1.03
0.79
1.28
a
0.617
9.25
8.10
1.75
1.40
. 1.16
0.99
0.82
1.22
e
0.690
9.60
9.00
1.94
1.54
1.37
1.05
0.93
1.37
(7 days)
0.639
1.11
1.83
J. 45
1.30
1.02
0.85
1.29
VII a
0.740
10.50
9.80
1.96
1.74
1.54
1.09
0.88
1.44
b
0.760
10.65
9.50
1.97
1.52
1,48
1.12
0.93
1.40
(8 days)
0.750
1.10
1.97
1.63
1.51
1.11
0.91
1.43
VIII a
0.800
10.50
9.25
1.90
1.57
1.46
1.21
0.91
1.41
h
0.805
10.90
9.20
2.13
1.70
1.58
1.17
0.85
1.49
b
0.822
10.45
. 9.80
1.94
1.60
1.49
1.17
0.92
1.42
c
0.849
10.50
9.70
2.05
1.70
1.56
1.22
0.95
1.50
k
0.870
10.95
9.70
2.18
1.72
1.62
1.22
0,99
1.55
d
0.898
11.45
10.15*
2.08
1.67
1.59
1.26
0.98
1.52
(9 days)
0.841
1.12
2.05
1.66
1.55
1.21
0.93
1.48
IX d
0.959
11.60
10.50
2.13
1.69
1.59
1.29
0.97
1.53
e
0.960
11.40
9.85
2.18
1.74
1.63
1.31
1.06
1.58
a
0.972
11.30
9.80
2.01
1.73
1.59
1.22
1.05
1.52
(10 days)
0.964
1.14
2.11
1.72
1.60
1.27
1.03
1.55
X a
1.033
11.90
9.60
2.35
1.68
1.61
1.28
0.95
1.57
b
1.036
11.85
9.85
2.25
1.78
1.62
1,31
1.01
1.59
e
1.051
12.05
10.05
2.23
1.69
1.60
1.32
1.09
1.59
(15 days)
1.040
1.21
2.28
1.72
1.61
1.30
1.02
1.59
XI a
1.107
12.00
10.00
2.40
1.78
1.66
1.45
1.13
1.68
b
1.189
12.50
10.10
2.32
1.98
1.82
1.40
1.12
1.73
c
1 . 193
12.65
10.35
2.27
1.88
1.78
1.48
1.24
1.73
d
1.195
12.60
10.15
2.44
1.96
1.70
1.35
1.13
1.72
(20 days)
1.171
1.28
2.36
1.90
1.74
1.42
1.16
1.72
XII c
1.234
12.30
10.40
2.44
1.88
1.70
1.42
1.22
1.73
a
1.273
12.45
9.80
2.58
1.92
1.72
1.31
1.26
1.76
1.253
1.23
2.51
1.90
1.71
1.37
1.24
1.75
XIII. a
1.301
13.00
11.10
2.48
1.84
1.69
1.36
1.08
1.69
g
1-.307
12.95
10.10
2.54
1.83
1.64
1.40
1.15
1.71
b
1.327
13.20
10.10
2.51
1.88
1.76
1.36
1.19
1.74
c
1.346
13.00
10.10
2.55
1.85
1.74
1.34
1.16
1.73
h
1.392
13.45
11.40
2.58
1.91
1.77
1.39
1.12
1.75
1.335
1.24
2.53
1.86
1.72
1.37
1.14
1.72
558
GROWTH OP THE CEREBRAL CORTEX
559
TABLE 6— Concluded
BRAIN WEIGHT
COEFFICIENT
THICKNESS OF
THE CORTEX (SAGITTAI, SECTION)
BRAIN WEIGHT GROUP
Diam.
L.F
on fresh
brain
Diam.
L.F
on slide
Loc.
I
Loc. II
Loc.
Ill
Loc. IV
Loc. V
Average
grams
mm.
vim.
mm.
mm.
m.m,.
mm.
mm.
mm.
XIV a
1.412
13.40
10.70
2.50
1.88
1.71
1.40
1.08
1.71
e
1.441
13.25
10.50
2.64
1.77
1.55
1.27
1.09
1.66
b
1.483
13.30
11.60
2.43
1.89
1.70
1.40
1.23
1.73
1.U5
1.22
2.52
1.85
1.65
1.36
1.13
1.70
XV a
1.530
13.70
11.30
2.56
1.83
1.74
1.34
1.13
1.72
b
1.542
13.50
11.40
2.53
1.79
1.61
1.30
1.18
1.68
c
1.552
13.70
10.70
2.56
1.92
1.69
1.40
1.23
1.76
d
1.573
13.70
11.20
2.65
1.98
1.76
1.39
1.21
1.80
e
1.574
13.75
11.20
2.70
1.94
1.78
1.44
1.30
1.83
1.554
1.22
2.60
1.89
1.72
1.37
1.21
1.76
XVI a
1.642
14.10
11.30
2.78
2.05
1.80
1.38
1.19
1.84
g
1.643
14.65
11.50
2.72
1.79
1.68
1.28
1.11
1.72
c
1.647
13.75
11.40
2.78
1.84
1.68
1.35
1.16
1.76
e
1.690
13.65
10.90
2.62
1.94
1.76
1.30
1.09
1.74
1.656
1.25
2.72
1.91
1.73
1.33
1.14
1.77
XVII f
1.720
14.90
11.80
2.84
1.81
1.72
1.34
1.16
1.77
a
1.721
13.90
11.40
2.67
1.91
1.78
1.38
1.19
1.79
b
1.730
13.85
11.50
2.67
2.07
1.87
1.46
1.28
1.86
c
1.731
14.30
11.70
2.71
1.98
1.67
1.30
1.15
1.76
1.726
1.23
2.72
1.94
1.74
1.37
1.19
1.79
XVIII c
1.817
15.20
12.10
3.06
1.91
r.77
1.36
1.24
1.87
a
1.844
14.00
11.90
2.77
2.09
1.94
1.44
1.21
1.89
e
1.855
15.05
12.10
2.82
1.90
1.72
1.46
1.24
1.83
1.839
1 .23
2.88
1.97
1.81
1.42
1.23
1.86
XIX a
1.924
15.40 1 12.30
2.89
1.85
1.71
1.35
1.20
1.80
1.9U
1.25
2.89
1.85
1.71
1.35
1.20
1.80
XX a
2.039
15.10
12.80
2.82
1.86
1 72
1.36
1.22
1.80
h
2.069
15.55
13.30
2.80
1.99
1.72
1.33
1.16
1.80
2.054
1.19
2.81
1.93
1.72
1.35
1.19
1.80
560
NAOKI SUGITA
TABLE 7
Showing the corrected values of the cortical thickness in the frontal section for each individual and for each brain weight group. The data for the correction-coefficients are indicated separately for each brain and the coefficicn' is g'rcn explicitly In the average for each group. Group averages in italic.
1
COEFFICIENT
THICKNESS ■OF THE CORTEX (FRONTAL SECTION)
BRAIN
BRAIN WEIGHT
WEIGHT GROUP
Diam. W.D
on fresh brain
Diam. W.D on slide
Loc. VI
Loc. VII
Loc. VIII
Average
grams
m m ■
m m .
mm.
}>(ill.
m m .
m m .
I a
0.153
6.45
5.92
0.51
0.56
0.49
0.52
c
0.154
6.35
5.60
0.53
0.58
0.49
0.53
b
0.177
6.95
6.26
0.68
0.70
0.54
0.64
0.161
1.11
0.57
0.61
0.51
0.56
II a
0.213
8.40
6.95
0.88
0.99
0.65
0.84
b
0.221
7.95
6.50
0.67
0.62
0.54
0.61
c
0.261
7.80
7.48
0.72
0.81
0.66
0.73
d
0.271
7.75
6.40
0.82
0.91
0.71
0.81
e
0.288
8.55
6.60
0.96
0.97
0.76
0.90
(Birth)
0.251
1.19
0.81 .
0.86
0.66
0.78
III a
0.311
8.50
7.65
0.84
0.95
0.84
0.88
b
0.322
8.70
6.80
1.14
1.14
0.93
1.07
g
0.374
8.95
8.45
1.07
1.15
0.92
1.05
c
0.390
8.85
7.40
1.11
1.11
0.93
1.05
i
0.395
9.10
8.60
1.09
1.14
0.99
1.07
(2 days)
0.358
1.13
1.05
1 .10
0.92
1.02
IV h
0.400
9.00
8.50
0.97
1.09
0.88
0.98
a
0.402
9*10
7.90
1.17
1.27
0.97
1.14
c
0.420
9.00
8.15
1.07
1.16
0.91
1 05
i
0.443
9.15
8.40
1.12
1.26
0.95
1.11
d
0.459
9.50
7.85
1.25
1.38
0.98
1 20
e
0.466
9.30
9.25
1.18
1.29
1.07
1.18
(4 days)
0.432
1.10
1.13
1.24
0.96
1.11
V i
0.501
9.80
9.20
1.26
1.38
1 01
1.22
a
0.525
9.65
9.15
1.28
1.39
1.04
1.24
b
0.528
9.90
8.60
1.36
1.52
1.14
1.34
c
0.534
10.30
8.05
1.44
1 . 56
1.15
1.38
d
0.537
10.00
8.80
1.34
1 47
1.12
1.31
e
0.555
9.90
9.20
1.40
1.52
1.13
1.35
f
0.558
10.00
8.55
1.42
1.54
1.15
1.37
g
0.564
10.10
9.15
1.32
1.51
1.20
1.34
h
0.579
10.10
9.50
1.42
1.58
1.15
1.38
(6 days)
0.542
1.12
\
1.36
1 .50
1.12
1.33
{
TABLE 7— Continued
COEFFICIENT
THICKNESS
OP THE CORTEX (FRONTAL SECTION)
BRAIN
brain'
WEIGHT
WEIGHT GROUP
Diam. W.D
on fresh brain
Diam. W.D on slide
Loc. VI
Loc. VII
Loc. VIII
Average
grams
mm.
m.m.
mm.
mm.
TTiW,
mm.
VI c
0.610
10.15
8.50
1.64
1.73
1.31
1.56
a
0.617
10.55
8.30
1.62
1.72
1.19
1.51
e
0.690
10.60
9.40
1.67
1.72
1.34
1.58
(7 days)
0.639
1.19
1.64
1.72
1.28
1.55
VII a
0.740
11.00
9.20
1.92
1.92
1.47
1.77
b
0.760
11.20
9.00
1.82
1.85
1.43
1.70
(8 days)
0.750
1.22
1.87
1.89
1.45
1.74
VII a
0.800
11.15
8.40
2.08
2.05
1.39
1.84
h
0.805
10.60
8.30
2.04
2.05
1.44
1.84
b
0.822
11.85
10.20
1.92
1.95
1.59
1.82
c
0.849
11.40
9.90
1.81
1.92
1.48
1.74
k
0.870
11.45
9.40
2.00
2.12
1.52
1.88
d
0.898
11.75
9.90
1.84
2.02
1.60
1.82
(9 days)
0.8^1
1.23
1.95
2.02
1.50
1.82
IX d
0.959
11.80
9.70
1.98
2.03
1.44
1.82
e
0.960
12.15
10.00
1.92
2.07
1.60
1.86
a
0.972
11.95
9.80
2.03
2.19
1.48
1.90
(10 days)
0.964
1.22
1.98
2.10
1.51
1.86
X a
1.033
12.40
10.30
1.94
2.03
1.56
1.84
b
1.036
12.40
9.70
1.91
2.06
1.56
1.84
e
1.051
12.10
10.20
2.01
2.04
1.50
1.85
(15 days)
1.040
1.22
1.95
2.04
1.54
1.84
XI a
1.107
12.90
10.20
2.25
2.03
1.55
1.94
b
1.189
13.15
10.70
1.98
2.02
1.67
1.89
c
1.193
12.70
10.50
1.97
2.06
1.57
1.87
d
1.195
12.50
9.80
2.10
2.15
1.56
1.94
(20 days)
1.171
1.24
2.08
2.07
1.59
1.91
XII c
1.234
12.95
11.00
1.97
1.99
1.60
1.85
a
1.273
12.90
10.00
2.14
2.19
1.56
1.96
1.253
1.23
2.06
2.09
1.58
1 .91
XIII a
1.301
13.20
10.60
2.11
2.14
1.61
1.95
g
1.307
12.70
10.20
1.97
2.17
. 1.53
1.89
b
1.327
13.35
9.60
1.98
2.17
1.67
1.94
c
1.346
13.15
9.70
2.08
2.33
1.62
2.01
•h
1.392
13.10
11.20
1.98
2.09
1.68
1.92
1.335
1.28
2.02
2.18
1.62
1.94
561
THE JOURNAL OF COMPARATIVE NEUROLOGY, VOL. 28, NO. 3
562
NAOKI SUGITA
TABLE 7— Concluded
BR.\IN
BR.\1N WEIGHT
COEFFICIENT
THICKNESS
OF THE CORTEX (fRONT.VL SECTION)
WEIGHT GROUP
Diam. W.D
on fresh brain
Diam. W.D
on
slide
Loc. VI
Loc. VII
Loc. VIII
Average
gms.
ni »t .
mw.
VI )ll .
m m .
m m .
m m .
XIV a
1.412
13,65
10.30
2.17
2.33
1.63
2,04
e
1.441
13.10
9.50
2.07
2.30
1.53
1.97
b
1.483
13.80
10,80
2.03
2.25
1.65
1.98
1.U5
1.32
2.09
2.29
1.60
1.99
XV a
1.530
13.80
10,40
1.98
2.24
1.50
1,91
b
1.542
13.70
10.40
2.12
2.27
1,67
2.02
c
1.552
13.50
10.30
1.84
2.20
1,57
1,87
d
1.573
13.90
10.60
2.08
2.33
1,65
2,02
e
1.574
13.70
10.80
2.16
2.20
1.66
■ 2,01
1.554
1 .31
2.04
2.25
1.61
1.97
XVI a
1.642
13.80
11.20
1.92
2.31
1.68
1.97
g
1.643
13.40
9.50
1.79
2.17
1.68
1.88
c
1.647
14.00
11.00
2,02
2.22
1,71
1.98
e
1.690
13.45
9.60
1.82
2.25
1,64
1.90
1.656
1.32
1 .89
2.24
1.68
1.94
XVII f
i.720
13.50
10.00
1.88
2.23
1,53
1.88
a
1.721
14.00
11.00
1.83
2.23
1,60
1.89
b
1.730
14.70
12.20
2.02
2.25
1,62
1.96
c
1.731
14.40
11.80
1.88
2.17
1,56
1.87
1 .726
1 .26
1.90
2.22
1.58
1.90
XVIII c
1.817
14.00
10.40
1.91
2.15
1,54
1.87
a
1.844
15.00
12.40
2.15
2 36
1.62
2.04
e
1.855
14.30
10.60
1.96
2.37
1.63
1.99
1.839
1.30
2.01
2.29
1.60
1.97
XIX a
1.924
14.10 1 11.60
1.78
2.17
1.54
1.83
1.924
1.22
1.78
2.17
1.54
1.83
XX a
2 039
14.80
12.60
1.67
2.03
1 .55
1.75
b
2.069
14.60
12 40
1.60
1.95
1,53
1.70
2.054
1 .18
1.64
1.99
1.54
1.72
TABLE 8
Showing the corrected values of the cortical thickness in the horizontal section for each individual and also for each brain iveight group. The data for the correctioncoefficients are indicated separately for each brain and the coefficient is given explicitly in the average for each group. Group averages in italic
BRAIN WEIGHT GROUP
BRAIN WEIGHT
gms.
I
II f
0.288
g
0.296
(1 day)
0.292
III d
0.303
f
0.316
e
0.331
(2 days)
0.317
IV g
0.415
h
0.421
f
0.423
(3 days)
0.419
V j
0.520
1
0.535
k
0.541
n
0.563
m
0.569
(5 days)
0.546
VI d
0.613
b
0.650
(7 days)
0.631
VII d
0.728
c
0.794
(8 days)
0.761
VIII e
0.809
i
0.829
f
0.868
g
0.884
(9 days)
0.848
IX b
0.914
c
0.964
(10 days)
0.939
COEFFICIENT
Diam. W.Bon fresh brain
8.60 8.70
Diam.
W.B on
slide
7.30 8.40
1.10
8.65 9.20 9 20
7.75 7.30 7.20
1.21
9.60 10.00 10.00
.60 .30 .90
1.30
10.65 10.45 11 00 11.30 11.20 /
9.35 8.40 8.60 9.40 9.20
11.00 11.50
8.60 9.50
1.24
12.20 12.15
9.70 9.55
1.26
12.40 12.10 12.50 12.50
9.90 8.30 9.40 8.70
1.36
13.00 12.90
9.85 9.85
1.32
THICKNESS OF THE CORTEX (HORIZONTAL SECTION)
Loc. IX
1.05 1.08 1.07
1.16 1.26 1.31
1.24
1.58 1.72 1.71
1 .67
1.88 1.78 1.79 1.89 1.68 1.80
1.96 2.07
2.02
2.19 2.36
2.28
2.32 2.64 2.34
2.57
2.47
2.48 2.63
2.56
Loc. X
0.89 0.92 0.91
1.02 1.05 1.07 1.05
1.25 1.41 1.42
1.36
1.58 1.42 1,38 1.52 1.33 1.45
1.63 1.61
1.62
1.71» 1.85
1.78
Loc. XI
0.78 0.74
0.76
0.84 0.92 0.92 0.89
1.02 1.08 1.19
1.10
1.36 1.28 1.19 1.27 1 17 1 .25
1.40 1.38 1.39
1.48 1.62
1.55
1.44 1.66 1.66 1.80 1.64
1.66 1.73
1.70
Loc. XII
0.65 0.64 0.65
0.71 0.81 0.77
0.76
0.87 1.00 1.04 0.97
1.11 1.11 1.12 1.13 1.08 1 .11
1.15 1.27
1.21
1.34 1.35
1.35
1.35 1.55 1.46 1.51
1.47
1.63 1.60
1.57
T oc. XIII
0.48 0.47
0.48
0.49 0.62 0.57
0.56
0.76 0.86 0.66 0.76
0.77 0.72 0.78 0.81 0.78 0.77
0.72 0.94 0.83
1.11 0.97
1.04
1.03 1.06 1.10 1.12
1.08
1.03 1.16
1 .10
Average
77
0.77
0.77
0.84 0.93 0.93 0.90
1.10 1.21 1.20
1 .17
1.34 1.26 1.25 1.32
1 21 1.28
1.37 1.45
l.4t
1.60
1.56 1.75 1.70
1.74 1.69
1.71 1.82
1.77
563
TABLE 8— Concluded
BRAIN WEIGHT
COEFFICIENT
THICKNESS OF THE CORTEX (HORIZONTAL SECTION)
WEIGHT GROUP
Diam.
W.Bon fresh brain
Diam.
W.Bon
slide
Loc. IX
Loc. X
Loc. XI
Loc. XII
Loc. XIII
Average
gms.
mm.
mm.
mm.
m m .
m m ■
mm.
mm.
vim.
X d
1.028
13.00
10.00
2.56
1.81
1.79
1.64
1.13
1.79
c
1.035
13.10
8.80
2.89
2.16
1,79
1.67
1.19
1.94
f
1.098
12.80
9.80
2.79
1.92
1.83
1.64
1.11
1.86
(15 days)
1.054
1.36
2.75
1.96
1.80
1.65
1.14
1.86
•XI e
1.121
13.10 1 10.40
2.88
1.92
1.83
1.66
1.11
1.88
(19 days)
1.121
1.26
2.88
1.92
1.83
1.66
1.11
1.88
XII d
1.209
13.95
10.20
2.82
2.13
1.91
1.78
1.26
1.98
b
1.255
13.75
9.90
2.97
2.22
.1.88
1.71
1.23
2.00
e
1.257
14.05
10.50
2.76
2.03
1.83
1.70
1.19
1.90
1.240
1.36
2.85
2.13
1.87
1.73
1.23
1.96
XIII d
1.332
14.05
10.00
2.67
2.01
1.80
1.58
1.15
1.84
f
1.344
13.90
10.80
2.65
1.98
1.84
1.59
1.26
1.86
e
1.377
14.00
10.30
2.65
2.11
1.92
1.67
1.21
1.91
1.351
1.35
2.66
2.03
1.85
1.61
1.21
1.87
XIV d
1.448
14.00
10.75
3.06
2.03
1.86
1.61
1.17
1.95
c
1.461
13.95
10.60
2.60
2.12
1.93
1.66
1.29
1.92
1.455
1.31
2.83
2.08
1.90
. 1.64
1.23
1.94
XV f
1.533
14.25
11.20
2.73
2.04
1.82
1.62
1.16
1.87
g
1.599
14.40
11.30
2.56
2.03
1.90
1.71
1.26
1.89
1.566
1.27
2.65
2.04
1.86
1.67
1.21
1.89
XVI b
1.674
14.75
11.40
2.50
1.87
1.82
1.68
1.19
1.81
h
1.675
14.25
10.40
3.30
2.10
2.11
1.68
1.25
2 09
d
1.680
14.30
10.90
2.80
2.03
2.07
1.74
1.26
1.98
f
1.683
14.10
10.50
3.27
2.20
2.08
1.68
1.34
2.12
1.678
1.33
2.97
2.05
2.02
1.70
1.26
2.00
XVII e
1.723
14.40
10.80
3.45
1.79
1.88
1.55
1.19
1.97
d
1.738
14.45
10.50
2,90
1.88
1.88
1.58
1.18
1.88
1.730
1.35
3.18
1.84
1.88
1.57
1.19
1.93
XVIII b
1.802
14.50
11.20
2.65
2.13
1.96
1.77
1.19
1.94
d
1.844
14.70
11.40
3.08
2.05
2.03
1.70
1.29
2.03
1.823
1.29
2.87
2.09
2.00
1.74
1.24
1.99
XIX
1
XX c
2.004
15.10 1 11.60
3.30
2.26
2.26
1.83
1.38
2.21
2.004
1.30
3.30
2.26
2.26
1.83
1.38
2.21
30
23 2fa 24
Q
1 Q
2 Q
3
4
5
fc a
7
8 Q
9 J.
3 1
] 1
2 1
3 1
^ 1
5 1.
b 1
7 18 19 20 ^
Chart 3 Giving the corrected thickness of the cortex of the albino rat in sagittal section. Individual entries for the cortical thickness at localities I and V, and the average thickness of the sagittal section (localities I, II, III, IV and V) are given. Based on table 6. o, cortical thickness at locality I. Corrected. X, Cortical thickness at locality V. Corrected. •, Average thickness of the cortex in the sagittal section. Corrected.
For the horizontal section a different brain was necessarily used. In this instance, table 8, brain III d is first in the Group III. Here the correction-coefficient was obtained by formula (3) and the observed values from each of the five localities IX to XIII were corrected accordingly. It is by the use of the measurements thus recorded that the average thickness of the cortex of a brain about two days of age has been obtained, as shown in table 9.
The entire series has been grouped according to brain weight, beginning with the group 0.1 to 0.2 gram and progressing by increments of 0.1 gram up to 2.0 grams. The normal brain weight at birth lies between 0.2 and 0.3 gram.
24 22 20 18 lb 14 12
10
08 06 0.4 02
0.1 0.2 03 04 05 06 0.7
Q9 10 11 12 13 14 IS 16 IT 1.8 19 20 r»
Chart 4 Giving the average thickness of the cerebral cortex for each brain weight group at localities I, II, III, IV and V in the sagittal section and the average thickness for the five localities in the sagittal section, for each brain weight group. Based on table 6. ■ — ■ — (above the heavy line) Cortical thickness at locality I. Corrected. • — • — • (above the heavy line) Cortical thickness at locality II. Corrected. Cortical thickness at locality III. Corrected. • — • — • — (below the heavy line) Cortical thickness at locality IV. Corrected. ■ — • — (below the heavy line). Cortical thickness at localit}' V. Corrected.
• "S Average thickness of the cortex in the sagittal section for each brain
weight group. Corrected.
In each of the groups thus formed (twenty in tables 6 and 7, and eighteen in table 8), there are from one to nine brains in a group. In tables 6 and 7 the average is nearly four per group and in table 8 it is about two and a half.
For some groups the approximate average age is given in days, but for all of the groups there has been entered the average brain weight, the correction-coefficient and then the corrected thickness of the cortex at each locality in the section. Finally the average thickness of the cortex for the entire section is given.
0.1 Q2 Q3 04 05 06 07 Q8 09 10 H 12 13 1+ IS 16 IT 18 19 2.0 p"*
Chart 5 Giving the corrected thickness of the cerebral cortex of the albino rat in frontal section. Individual entries for the cortical thickness at localities VII and VIII, and the average thickness of the cortex in the frontal section for localities VI, VII and VIII are given. Based on table 7. o, Cortical thickness at locality VII. Corrected*. X, Cortical thickness at locality VIII. Corrected. •, Average thickness of the cortex in the frontal section. Corrected.
01 02 03 04 Q5 06 Q7
09 10 11 12 1.3 14 15 16 1,7 18 19 20 T'
Chart 6 Giving the average thickness of the cerebral cortex for each brain weight group at localities VI, VII, VIII in the frontal section and also the average thickness of the cortex at the three localities combined. Based on table 7.
Cortical thickness at locality VI. Corrected. • — —Cortical thickness
at locality VII. Corrected. • — • — • Cortical thickness at locality VIII. Corrected. • "F Average thickness of the cortex in the frontal section for each
brain weight group. Corrected.
11
2
3 Q
4 Q
5
fc Q
7
8
9 1
1
1 1
2 i
3 1
+ 1
5 1
& 1
7 [?, 1.9 20 r
Chart 7 Giving the corrected thickness of the cerebral cortex of the albino rat in horizontal section. Individual entries for the cortical thickness at localities IX and XIII, and also the average thickness of the cortex of the horizontal section at localities IX, X, XI, XII and XIII combined. Based on table 8. O, Cortical thickness at locality IX. Corrected. X, Cortical thickness at locality XIII. Corrected. •, Average thickness of the cortex of the horizontal section. Corrected.
By making tables 6, 7 and 8 in the form here used and by entering for each brain weight group the data for the correctioncoefficient, it is made possible for any one who so wishes to recover from the corrected values here given the values as obtained by direct observation on the shde (table 5), though, in some instances, small discrepancies result between the values thus calculated and the values given in table 5, owing to repeated averaging and the frequent dropping of fractions under 0.005 mm.
To obtain the average thickness in any brain weight group the values for the average thickness in sagittal, frontal and horizontal sections are again averaged, as shown in table 9. The
0.1 02 0.5 04 05 Q<) 07
09 10 11 12 13 H 15 Ifc 1.7 18 19 20
Chart 8 Giving the average thickness of the cerebral cortex for each brain weight group at localities IX, X, XI, XII and XIII in horizontal section and the average thickness for each brain weight group in horizontal section for the five localities combined. Based on table 8. ■ — • — (above the heavy line) Cortical thickness at locality IX. Corrested. • — • — » (above the heavy line) Cortical
thickness at locality X. Corrected. Cortical thickness at locality XI.
Corrected. • — • — • — (below the heavy line) Cortical thickness at locality
XII. Corrected. (below the heavy line) Cortical thickness at locality
XIII. Corrected. • •!! Average thickness of the cortex in the horizontal
section for each brain weight group. Corrected.
general average thickness of the cortex in any brain weight group was obtained by adding the three averages for each brain weight group and dividing the sum by three. The averages of the brain weights were copied from tables 6 and 7 for the sagittal and frontal sections and from table 8 for the horizontal sections. The general average brain weight is obtained by adding the values in table 6 and in table 7 to the value in table 8 and dividing the sum by three.
This table 9 is valuable as a standard for the discussion of the actual growth of the cortex in thickness according to brain growth (weight), because these values have been corrected to the fresh condition and may be regarded as giving a truthful picture of the thickness of the cerebral cortex of the albino rat from birth to maturity.
TABLE 9 Showing the average (corrected) thickjiess of the cerebral cortex in the al'jino rat by brain weight groups
BRAIN
SAGITTAL
SECTION
FRONT.\L SECTION
HORIZONTAL SECTION
AVERAGE
WEIGHT
GROUP
Brain
Thick
Thick
Brain
Thick
Brain
Thick
Approxi
weight
ness
ness
weight
ness
weight
ness
mate age
grams
mm.
mm.
grams
m7n.
grams
m m .
days
I
0.161
0.52
0.56
II
0.251
0.67
0.78
0.292
0.77
0.265
0.74
B
III
0.358
0.90
1.02
0.317
0.90
0,344
0.94
2
IV
0.432
0.99
1.11
0.419
1.17
0.428
1.09
4
V
0.542
1.14
1.33
0.546
1.28
0.543
1.25
6
VI
0.639
1.29
1.55
0.631
1.41
0.636
1.42
1
VII
0.750
1.43
1.74
0.761
1.60
0.754
1.59
8
viir
0.841
1.48
1.82
0.848
1.69
0.843
1.66
9
IX
0.964
1.55
1.86
0.939
1.77
0.956
1.73
10
X
1.040
1.59
1.84
1.054
1.86
1.045
1.76
15
XI
1.171
1.72
1.91
1.121
1.88
1.154
1.84
20
XII
1.253
1.75
1.91
1.240
1.96
1.249
1.87
XIII
1.335
1.72
1.94
1.351
1.87
1.340
1.84
XIV
1.445
1.70
1.99
1.455
1.94
1.448
1.88
XV
1.554
1.76
1.97
1.566
1.89
1.558
1.87
XVI
1.656
1.77
1.94
1.678
2.00
1.663
1.90
XVII
1.726
1.79
1.90
1.730
1.93
1.727
1.87
XVIII
1.839
1.86
1.97
1.823
1.99
1.833
1.94
XIX
1.924
1.80
1.83
XX
2.054
1.80
1.72
2.004
2.21
2.037
1.91
The average thickness of the cerebral cortex of the adult albino rat is 1.88 mm., as obtained by averaging the values for the Groups XI to XX, in which stages the cortex may be considered as having reached about its full thickness.
The following chart 9 is based on table 9. This chart is very interesting and important for the further consideration as a standard picture of the cortical development and to it I shall refer in tbe following chapter.
The increase of the cortical thickness according to age, instead of brain weight, is given graphically in chart 10, which was plotted by using the above data, converted by calculations, based on the Age-Body weight" and the Body weight — Brain weight" formulas given in "The Rat" (Donaldson, '15). This chart shows in a dotted line also the brain weight curve according to age.
Ql Q2 0.3 0.4 0.5 Q6 07
0.9 10 11 12 13 14 15 lb 17 18 19 M r
Chart 9 Giving the corrected thickness of the cerebral cortex in sagittal, frontal and horizontal sections and the general average thickness of the cortex for the three sections combined, on brain weight groups. Based on table 9. • — • — • — S. Average thickness of the cortex in sagittal section. Corrected.
F. Average thickness of the cortex in frontal section. Corrected.
H. Average thickness of the cortex in horizontal section. Corrected.
• "A. General average thickness of the cortex for all three sections.
Corrected.
On examining chart 9 (for the cortical thickness on brain weight), I was inclined in the first instance to conclude that the course of the cortical growth in thickness should be divided into three phases; that is, a first phase during which the brain weight increases from 0.25 gram (at birth) to 0.75 gram, and during which the increase in thickness is rapid; a second phase during which the brain weight increases from 0.75 gram to 1.15 grams, when the rate of cortical increase diminishes; and a third final phase of very slow increase. But this division according to the brain weight is not suitable for comparative studies. If, however, we examine chart 10 (cortical thickness on age), it will be readily seen to be more advisable to divide the developmental phases of the cortical growth according to age rather than according to the brain weight; thus, according to age, the first phase of the rapid increase covers the first ten days after birth (brain weight 0.25 to 0.95 gram), the second phase of slower increase covers the following ten days (brain weight 0.95 to 1.15 grams) and the third phase of very slow increase in the thickness of the cortex lasts from twenty-first day to the ninetieth day and, if necessary, a fourth phase for the remainder of the fife span might be added.
Cortical thickness in Brain weight in gn
8 10 \% \\ 16 18 20 22 24- 26 28 30 32 34 56 3«
An, \n days.
Chart 10 Showing the thickness of the cerebral cortex and the brain weight of the albino rat according to age, up to 38 days. The heavy line gives the mean cortical thickness in millimeters. The dotted line gives the brain weight in grams.
As is seen in chart 10, the increase of the cortex in thickness according to age follows closely, during the first two phases, the increase of the brain weight according to age.
IX. Discussion
Table 5 and chart 1 show the mean observed values on the slide, while tables 6 to 9 and charts 3 to 9 give in detail the corrected values which are assumed to be the actual thickness of the cortex in fresh condition. The corrected data will be taken as the basis for the discussion which follows.
Brains having almost the same weight rarely show exactly the same cortical thickness, but differ somewhat in this character. This may be due partly to the technical differences during preparation, but it also means probably some individual variation. Generally speaking, the thickness of the cerebral cortex is well correlated with the brain weight, so that, as a rule, the cortex increases its thickness as the brain increases in weight. With the albino rat, the first ten days after birth is a period of rapid growth especially for the central nervous system, so that, at the age of ten days the brain weight has attained nearly four times its weight at birth, growing from 0.25 gram to 0.95 gram, while the body weight has increased only 2.4 times — from 5 grams at birth to 12 grams on the tenth day. Accordingly, the cerebral cortex which follows the brain weight also shows a very rapid increase during this period. In this case, as in other cases of rapid growth, considerable individual variations naturally appear. For example, although 'V a' and 'V b' (table 6) are nearly alike in brain weight, the thickness of the cortex differs on the average as much as 0.10 mm. in the sagittal sections. Again, TV d' and TV e' with brain weights almost the same, show a difference of 0.12 mm. in the average thickness of the sagittal sections. These variations amount to ± 5 per cent of the mean value for the cortical thickness.
Even thirty days after birth, when the phases of the rapid growth of the cortex have already passed, the individual variation in the cortical thickness is by no means low. During the second and third months after birth, the body weight increases from 30 grams to 150 grams or 400 per cent, while the brain weight increases only from 1.30 grams to 1.70 grams or 30 per cent. Through this period, the thickness of the cortex gains but 2 per cent or less (0.03 to 0.05 mm.). The variations during this period are illustrated by the following records.
Making the determination of the average deviation from the mean thickness of the cortex for Groups XIII to XVII inclusive (tables 6 and 7), it appears that for the sagittal sections this deviation is ±2.9 per cent and for the frontal sections ±2.7 per cent, while for the equivalent groups (table 8) giving the values for the horizontal sections is also ±2.7 per cent. From these results we conclude that after the period of rapid growth the thickness of the cortex follows closely the brain weight.
On the basis of chart 10 (the cortical thickness on age) , I have concluded that during the earlier part of the life of the albino rat we may recognize three phases, in the growth of the cortex in thickness, namely;
1) First phase, from birth to the tenth day. (The brain weight increases during this phase from 0.25 gram to 0.95 gram).
2) Second phase, from the tenth day to the twentieth day. (The brain weight increases during this phase from 0.95 gram to 1.15 grams).
3) Third phase, from the twenty-first day to the ninetieth day. (The brain weight increases during this period from 1.15 grams to 1.80 grams).
During these phases the various localities, at wljich the thickness of the cortex has been measured, grow at different rates. The one which shows the most rapid development in thickness throughout life, is the locality I at the frontal pole (fig. 2). The cortex at locality I attains at the end of the first phase 2.5 times, at the end of the second phase 2.8 times and at the end of the third phase 3.2 times the thickness which it had at birth. At localities II, III, IV, X, XI and XII (figs. 2 and 6), namely those parts of the cortex near the middle of the brain, the development of the cortical thickness is similar. Thus these reach at the end of the first phase on the average 2.3 times, at the end of the second phase on the average 2.5 times and at the end of the third phase on the average 2.6 times the initial thickness at birth. The locality VI, which is situated at the margin of the sagittal fissure, and the locality VII, which represents the parietal region, show a relatively rapid development in the first phase, attaining at the end of that phase 2.45 times the thickness at birth, while at the end of the second phase they have attained
TABLE 10
Giving for the three sections, the thickness of the cerebral cortexin eachlocality at the beginning and the end of each of the three phases and also the percentages of gain in thickness during each phase. The data on thickness are taken from tables 6, 7 and 8. The average percentage gain in thickness for each section was computed by using the average of the values for the observed thickness for each locality. The general average percentages in the last line of the table ivere obtained by using the mean of the averages for thickness in the three sections, giving the average values for each sqction the same statistical weight only 2.6 times. But, after this phase locahty VI appears even to decrease sHghtly, while the locahty VII is still increasing.
SECTION
LOCALITY
THICKNESS OF CORTEX AT
BIRTH
(group
II)
GAIN DURING FIRST PHASE OF 10 DATS
THICKNESS OF CORTEX AT 10 DAYS
(group
IX)
GAIN
during
SECOND PHASE OF 10 DATS
THICKNESS OF CORTEX AT 20 DAYS
(group
XI)
gain
DURING THIRD PHASE OF 70 DATS
THICKNESS OF CORTEX AT 90 DAYS
(group
XVIII)
Sagittal section ■
I
II III
IV V
mm.
0.85 0.77 67 0.56 0.48
per cent
-M48 + 123 + 139
+ 127 + 114
mm. 2.11 1.72 1.60 1.27 1.03
per cent +12 + 10 + 9 + 12 + 13
mm.
2.36 1.90 1.74 1.42 1.16
per cent +22 + 4 + 4 + + 6
mm.
2.88 1.97 1.81 1.42 1.23
Average
0.67
+ 131
1 .55
+ 11
1.72
+ 8
1.86
Frontal section
VI
VII
VIII
0.81 0.86 0.66
+ 144 + 144 + 129
1.98 2.10 1.51
+ 5 +
+ 5
2.08 2.08 1.59
- 3 + 10
+ 1
2.01 2.29 1.60
I
Average
0.78
+ 138
1.86
+ 3
1 91
+ 3
1.97
Horizontal section. . . \
IX
X
XI
XII
XIII
1.07 0.91 0.76 0.65 0.48
+ 139 + 110 + 124 + 141 + 129
2.56 1.91 1.70 1.57 1.10
+ 12 + 5 + 8 + 6 + 5.
2.88 2.001 1.83 1.66 1.16
+ 8 + 5 + 9 + 5
+ 7
3.101 2.09 2.00 1.74 1.24
Average
0.77
+ 130
1.77
+ 7
1.90
+ 7
2.03
General average
0.74
+ 134
1.73
+ 6
1.84
+ 6
1.95
- 1 As the observed values at these localities in these groups have fallen below those in the foregoing and the following groups, I used in this table the values based on the average of all three groups.
Table 10 gives the rapidity of the gain in the cortical thickness at each locality and for each of the three phases, according to the data in tables 6, 7 and 8. The column designated as gain during the first phase" shows the percentage value of the thickness at the end of this phase as compared with the thickness at birth. The column designated "gain during the second phase" shows corresponding value for the second phase as compared with the thickness at the beginning of this phase. Similar in arrangement is the column giving the gain during the third phase. This table 10 shows very clearly the relative rapidity of growth at every locality and supports the interpretations presented above.
Speaking generally, the entire cortex, as represented by the thirteen locahties from different parts of brain, shows very rapid development during the first phase (see general average in table 10), especially at the frontal pole and along the mid-dorsal aspect of the frontal section (localities VI and VII). The parietofrontal parts (represented by locahties II and X) are somewhat slow in development compared with those on either side of them.
Through the second phase, the parts showing the most rapid development are also the frontal pole (represented by the locahties I and IX) and the parieto-occipital parts (Vepresented by the locahties IV and V), which were slow in starting, and the slowest growth is by the cortex which appears in the frontal section (represented by the localities VI, VII, and VIII). The growth at the locality XIII is also slow. This latter region has an heterogeneous structure of cortex, displaying a special type of cell-lamination, as shown in figure 6, and this may be associated with the retardation in its development in thickness. Remarkable is the fact that all the localities measured on the frontal sections, namely, the localities VI, VII and VIII, show relatively slow development during the second phase, having already attained nearly their full thickness at the end of the first phase. This is equivalent to saying that they are precocious.
In the third phase, there is some growth, except at the localities IV and VI. The locahty VI, as remarked above, appears to decrease somewhat in thickness during this phase and the locahty VII, which represents typical extra -limbic type of cell-lamination of the parietal part of hemispher„\ makes a considerable progress throughout the last phase. Th3 most marked growth is made, however, at the frontal pole, in the localities I and IX (charts 3, 4, 7 and 8).
From chart 2, which shows the development of the entire brain in each diameter, it will be seen that, after the brain has attained 1.0 gram in weight, the rapidity of growth in length (the sagittal diameter) largely surpasses that in breadth (the frontal diameter), a phenomenon possibly associated with the growth changes in the central nuclei, and with the rapid and continuous development of the cortex at the frontal pole.
At the locality III, the growth in thickness follows very closely the average thickness for the sagittal sections, and in the same way at the locality XI the growth in thickness follows the average thickness for the horizontal sections.^
- 3 Incidentally, I made a series of sections from the rat fetus of 18 days (body length from neck to buttocks average 1.95 cm., body weight average 1.0 gram) by the uniform technique above presented. When examined in the sagittal sections of the entire body, four main layers in the entire ventricular wall of the brain are distinguished, for example, (1) the lamina zonalis ('Randschicht'), (2) the lamina corticalis ('Rindenschicht'j, (3) the lamina intermedialis ('Zwischenschicht') and (4) the matrix. The average thickness of the entire wall of the hemisphere is 0.38 mm., and the lam. cort., which does not yet show any cell lamination, measures only 0.06 mm., consisting of five or six rows of the cells (the matrix 0.13, the lam. intermed. 0.16, the lam. cort. 0.06, the lam. zon. 0.03 mm. on the average in the sagittal sections). But in the newborn the thickness of the cortex has increased already to 0.6 mm. on the average in the sagittal sections (on slide), namely about ten times in thickness during the last four days of gestation.
Table 11 shows the localities arranged in the order of their cortical thickness at birth. In five cases, two localities close to one another and similar in structure are grouped together and the average thickness given. The order of the localities thus arranged by increasing cortical thickness remains unchanged at maturity. In this table, the ratios in both groups between the values of the same locality at birth and at maturity are roughly similar and the ratios between values of any two localities in the same age group are all almost equal. This indicates that the proportional thickness at any region of the cerebral cortex to that of any other region is quite constant throughout the growth of the brain. Moreover it indicates that Ihe thickness of the cortex at maturity is directly related to the thickness found at birth and from this we infer that the process of thickening is similar in the several localities but that the amount of material (number of cells) involved in the process differs.
TABLE 11
Showing the relation between the initial and final thickness of the cortex at the several
localities. The order of thickness at maturity is the same as the order of
thickness at birth
GROUP II (at BIBTh)
GROUP XVIIl (at maturity)
LOCALITY
Thickness of
cortex at each of
localities
Average by locality group
Thickness of
cortex at each of
localities
Average by locality group
V and XIII
IV
XII and VIII
III and XI
VI
II and X
VII I and IX
mm.
0.48 and 0.48
0.56 0.65 and 0.66 0.67 and 0.76
0.81 0.77 and 0.91
0.86 0.85 and 1.07
mm.
0.48 0.56 0.66 0.72 0.81 0.84 0.86 0.96
mm.
1,23 and 1.24
1.42 1.74 and 1.60 1.81 and 2.00
2.01 1.97 and 2.09
2.29 2.88 and 3.10
7nm.
1.24
1.42
1.67
1.91
2.01
2.03
2.29
2.99
Thickness of cortex according to sex
No sex difference in the thickness of the cortex has been detected. Among the 125 rats, employed in this study, there are 28 females, as indicated in tables 1 and 2. Table 12 shows the comparison of the thickness of the cortex, grouped by sex. Examining this table, it is seen that in Groups III to XIII, on all kinds of sections, there can be detected no difference due to sex, because the differences, greater than the probable error, in the figures within each group can be explained by the differences in the average brain weight. But, Group XVII on the sagittal sections and Groups XIII and XVII on the frontal sections show
GROWTH OF THE CEREBRAL CORTEX
579
TABLE 12 Showing the thickness of the cerebral cortex according to sex, within each brain weight group. Data taken from tables 6, 7, and 8. The average thickness of the sagittal and frontal sections and that of the horizontal section are separately given, with the average brain weight for each brain weight group examined
MALE
FEMALE
Brain weight
Sagittal
Frontal
Frontal
Sagittal
Brain weight
grams
mm.
m,m.
m?«.
mm.
grams
III
0.349
0.87
1.01
1.07
0.99
0.395
V
0.539
1.13
1.32
36
1.15
0,553
VI
0.612
1.25
1.54
58
1.37
0.690
VIII
0.829
1.47
1.82
82
1.52
0,898
Sagittal and frontal sec
IX
0.966
1.53
1.86
86
1.58
0.960
tions
XII XIII
1.234 1.320
1.73 1.72
1.85 1.95
96 92
1.76 1.75
1 273
1.392
XV
1.530
1.72
1.91
98
1.77
1.560
XVI
1.666
1.79
1.94
93
1.74
1.645
XVII
1,725
1.83
1.93
88
1.77
1.726
Brain weight
Horizontal
Horizontal
Brain weight
grams.
mm.
mm.
grams
III
0.317
0.86
0.93
0.316
VIII
0.835
1.67
1.74
0.884
X
1.066
1.90
1.79
1.028
XII
1.233
1.94
2.00
1.255
Horizontal, sections
XIII
1.338
1.85
1.91
1.377
XIV
1.461
1.92
1.95
1.448
XVI
1.679
1.97
2.04
1.678
XVII
1.738
1.88
1.97
1.723
XVIII
1.844
2.03
1.94
1.802
some excesses in favor of male. Groups XIV, XVI and XVII on the horizontal sections also show some excesses in favor of female. These differences, however, lie within the limits of individual variation, and hardly can be regarded as suggesting a difference in cortical thickness due to sex. Therefore, I conclude that there exists no sex difference in cortical thickness when brains of like weights are compared. But, if either body weight or body length are taken as the standard for comparison, a sex difference in cortical thickness appears in favor of male, because the brain weights under such conditions are higher in the males than in the females.
The increase in the average thickness of the cortex
According to charts 9 and 10, the growth curve of the cortical thickness shows many features in its course. In the first phase, previously mentioned, during which the brain weight increases from 0.25 gram to 0.95 gram, the curve rises rapidly smd, steadily. If we assume that, throughout this phase, the specific gravity of the brain substance remains unchanged and the various parts of the brain grow similarly in all dimensions, then the cerebral cortex should increase in thickness in proportion to the cube root of the brain weight (cf. also table 14 and chart 11). But in fact, the relative thickness of the cortex at the end of this phase is 2.34 or almost exactly equal to the square of the cube root (1.53) of the brain weight (volume). If the fact is
TABLE 13
Ginni] the absolute increase in thickness of the cerebral corte.r. during each phase of development, accompanied by the average increase per day during each phase and the ratios of this increase in the three phases. Data from table 10
PHASE
ABSOLUTE INCREASE IN THICKNESS
INCREASE PER DAY
R.\TIOS
First phase (Birth to 10th day)
Second phase (10th to 20th day)
Third phase (20th to 90th day)
mm.
0.99 (1.73-0.74) 0.11 (1.84-1.73) 0.11 (1.95-1.84)
Vim.
0.0990 0.0110 0.0016
62 7 1
recalled that in this first phase the increase of the brain weight according to age has been comparatively rapid, it will be seen that the growth of the cortex in thickness is very rapid indeed.
In the second phase, during which the brain weight increases from 0.95 gram to 1.15 grams (from the tenth day to the twentieth day after birth), the slope of the curve diminishes markedly, and, in the third phase, after the twentieth day, it runs almost parallel to the base line, showing but a slight gain during further brain growth.
If the rates of increase of the cortical thickness in the three phases are compared in the terms of absolute increase per day, the following values appear (table 13).
Thus the rate of increase during the first phase is 62 times as rapid as that during the third phase and the rate during the second phase 7 times as rapid as that during the third phase.
Three changes are occm-ring during these phases: (1) cell multiplication and immigration, (2) cell enlargement, represented by the growth of the cell body, and (3) the production of dendrites and of the axon, the latter representing the larger mass of substance.
AUeii ('12) has given the following figures as to the number of mitoses per cubic millimeter in the cerebrum of the albino rat at certain levels, selected in frontal sections. These show that cell production runs down rapidly between the first and second phases as follows.
FIRST PHASE
SECOND PHASE
Age (davs^
1 4 6 430 447 193
12 20 20
Number of mitoses
37 27 18
We may conclude from this that many more new cells are contributed in the first phase than in the second, but the data do not permit us to judge of the absolute amount of increase from this source.
By far the most important contribution to the cortex comes from the transitional layers of cells, the elements of which are rapidly added to the cortex during the early days of post-natal life.
According to another series of my studies, the cell size of the pyramids, for example, increases during the first phase in the length of cell body from 17 micra to 20 micra; about 18 per cent gain. Furthermore, the intercellular structures are also steadily increasing at this phase, and the cells become more and more separated from each other. These facts taken all together fit very well with the rate of 62 as given by my data.
As seen from chart 9, the cerebral cortex reaches within about 4 per cent of its full thickness at the end of the second phase (weaning time), when the brain weighs 1.15 grams or somewhat more than half its mature weight. After the end of the second phase, the cortex gains in thickness very slowly though continuously throughout the first year of life, while the brain continues to increase in weight according to age much more rapidly, so that, in the full grown rat, whose body weight amounts to more than 200 grams, the cortical thickness attains on the average nearly 1.94 mm. The general average thickness of the groups XI to XX is 1.88 mm. (table 9).
TABLE 14
Showing (column> B) brain weights, {column C) their ratios to the initial weight at birth, {column D) the cube roots of the numbers given in column C, indicating roughly the rate of increasing size, {column E) the average thickness of the cerebral cortex corresponding to the given brain weights and {column F) their ratios to the initial cortical thickness at birth, in every group
A,
B
c
D
E
F
Group
Brain weight
Ratio
Cube root
Average thickness
Ratio
grams
mm.
II
0.265
1.00
1.00
0.74
1.00
III
0.344
1.30
1.09
0.94
1.27
IV
0.428
1.62
1.17
1.09
1.48
v
0.543
2 05
1.27
1.25
1.69
VI
0.636
2.40
1.34
1.42
1.92
VII
0.754
2.85
1.42
1.59
2.15
VIII
0.843
3.18
1.47
1.66
2.25
IX
0.956
3.61
1.53
1.73
2.34
X
1.045
3.94
1.58
1.76
2.38
XI
1.154
4.36
1.63
1.84
2.49
XII
1.249
4.72
1.68
1.87
2.53
XIII
1.340
5.07
1.72
1.84
2.49
XIV
1.448
5.47
1.76
1.88
2.54
• XV
1.558
5.88
1.81
1.87
2.53
XVI
1.663
6.28
1.85
1.90
2.57
XVII
1.727
6.52
1.87
1.87
2.53
XVIII
1.833
6.92
1.91
1.94
2,62
XX
2.037
7.68
1.97
1.91
2.58
Table 14, which is based on table 9, presents the relations existing between the increase of the brain weight and the increase of the cortical thickness. The figures in column B of table 14 show the average brain weights by groups. Columr C shows the ratio of the brain weight of each group compared with the initial brain weight at birth. Column D shows the cube roots of the ratios given in column C, values which may be taken as representing the rate of increase in one dimension of the brain, if we neglect the shght increase in the specific gravity of the brain substance with advancing age and assimae that the brain form is similar throughout the series. Column E shows the absolute thickness of the cortex in each group and column F the ratios of the cortical thickness for each group, compared with the initial cortical thickness at birth.
Chart 11 A comparison of the growth curves of the cortical thickness, as observed, with the theoretical growth curve (c) of one diameter of the brain of the albino rat, (c) being the cube root of the ratio of the brain weight (Table 14). The cortical thickness and the length of one diameter of the brain at birth were taken as unity on the ordinate. On the abscissa the ratio of brain weight is entered. The dotted line is a theoretical curve which the cortical thickness would have followed if the cortical thickness at 20 days of age were taken as the starting point and it had increased at the same rate as the growth of the brain in diameter. X and X X mark respec tively the ends of the first and the second phases of development in cortical thick ness. Based on table 14.
On comparing the data in column F with those in column D, it will be seen at once that the increase in the thickness of the cortex is much more rapid than the increase in the diameters of the brain. Chart 11 visualizes the relations given in table 14, X and X X showing respectively the ends of the first and the second phases. The graph marked with 'C was plotted to show the cube root values given in column D. During the first phase, the cortex develops very rapidly, while during the second phase the increase of the cortex in thickness is similar to the increase of the brain in one diameter. If the thickness of the cortex at the end of the second phase were taken as the starting point of the third phase, and if the cortex continued to grow in thickness as during the second phase, then the increase in cortical thickness would have taken the course given by the dotted line. But the course of the actual increase, as shown by the heavy line graph, is very slow indeed. The cortex at this phase grows mainly in area. This agrees with the graph in chart 9 by which it has been shown that the average thickness of the cortex has nearly ceased to increase at the end of the second phase.
According to another series of studies, it has been found that the cells of which the cortex consists do not all reach their full size at the end of the second phase. Though a number of them have reached their full size before this time, most of the remainder are about midway in their development. Though some of the pyramids in the third layer have in this phase already attained their full size, yet their protoplasmic structure is not mature, as is shown by their staining reaction. The large ganglion cells in the fifth layer have not yet reached their full size, many of them being yet only midway in enlargement, and increasing in volume continuously through the third phase. Allen ('12) has shown that in the second phase the number of mitoses is already very small. I assume therefore that, in the second phase, the increase in the thickness of the cortex is caused chiefly by the enlargement of cell bodies, the production of cell branches and to a small extent by the deposition of myelin. Through the third phase, the brain continues to increase in volume according to age, and the cortex, which has almost ceased to grow in thickness, must however increase in area, as the hemispheres enlarge. Mitosis having almost ceased at the end of the second" phase, this increase in area must be due mainly to an increase in the diameters of the cell bodies and to the increase in the number and the size and the myelination of the fibers. This increase in area after the end of the second phase is very considerable. When the weight of the brain increases from 1.15 grams to 2.03 grams (table 14), the area increases some 46 per cent and it is this extension of area which is accomplished by the cortex, after growth in thickness has come nearly to an end. A detailed study of the manner in which this extension is accomplished must be reserved for another occasion. A word may be said however regarding the age relations of myelination in the rat's brain.
In his study on the myelination of the central nervous system of the albino rat, Watson ('03) found in the cerebrum the first myelination or investment of the axons with myelin sheaths, as indicated by the substance which stains with the Weigert-Pal's method, to begin at the ages given below.
Age of the beginning Localities in cerebrum of myelination
Capsula externa 11th day.
Stria olfactoria lateralis 14th day.
Corpus striatmn 14th day.
Corpus callosum 14th day.
Radiation into the cortex 14th day.
Commissura anterior 17th day.
Thalamus . .' 17th day.
The fibers radiating into the cortex myelinate very slowly, however, so that but few are to be seen till after twenty-fifth day. This age, the twenty-fifth day, would correspond to the early part of the third phase.
The fact that the cortex attains nearly its full thickness before the radiating fibers are myelinated should mean that the organization of the cortex occurs while growth in thickness is in progress. After this organization has been made, then myelin begins to appear around the axons, increasing their diameter. The increase in cortical area during and after the third phase must, therefore^ be caused principally by the enlargement of the cell bodies, the increase in the diameter of the axons and the formation and enlargement of the myehn sheaths.
This conclusion is supported by the table 74 in The Rat" (Donaldson, '15) which gives the percentage of water in the albino rat brain. From the values in that table, the mass of dry substances has been calculated and results are plotted according to brain weight in chart 12. In the first phase of the cortical development, the solids of the brain increase proportionally to the brain weight, but after the middle of the second phase (brain weight 1.00 grams) and through the third phase, they increase much more rapidly, again decreasing in rate at about 35 days after birth (brain weight 1.40 grams). This means clearly that from the middle of the second phase (about 15 days of age) some new substances begin to be deposited rapidly in brain, i.e., myelination is in progress. Looking at chart 26 given in "The Rat" (Donaldson, '15), we see that the percentage of water in the brain decreases comparatively slowly during the first ten days after birth, then, from the tenth day, decreases rapidly till the thirtieth day, after which the decrease becomes slow again. At the sixtieth day after birth, the brain (weight 1.60 grams, percentage of water ca. 79 per cent) has reached nearly to the stage of the adult in percentage of water. This indicates that myelination is going on energetically between the tenth and the thirtieth day after birth. The myelination in the cortical radiation begins late, accelerating its rate after the twentieth day.
Bringing together the foregoing observations and inferences, we may make the following statements concerning the growth changes in the cerebral cortex during the three phases which have been recognized.
The first phase covers the first ten days after birth. This phase represents the period in which the thickness of the cortex increases rapidly by means of both cell immigration and multiplication and cell enlargement. If the data of the Group I (tables 1, 3, 5, 6, 8, 9) from rats before normal birth are also taken into consideration, it is evident, as shown by the first entries on Charts 1, 3, 4, 5, 6 and 9, that the increase of the cortical thickness is equally rapid just before birth.
The second phase extends from the tenth day to the twentieth day after birth. During this phase the cortex receives but few new cells, but the thickness of the cortex increases chiefly by enlargement of cells already present and the developmental lengthening of axons, the rate of the increase in cortical thickness being just about equal to the increasing rate of brain size in one
0%
OA
0.6
as
io
i^
u
i.6
n
T'
Chart 12 Showing the absolute weights of the dry substance (in grams) in the brain of the albino rat according to the brain weight (in grams). Based on the data given in table 74 in "The Rat" (Donaldson, '15). X, the middle of the second phase; XX, the early part of the third phase.
diameter. During this phase, the cortex becomes provided with nearly all of the cellular elements necessary to it at maturity. By the end of this phase, the cortex has attained almost its full thickness, the brain weight, however, being only a little more than one-half that of the mature brain. Myelination has been in progress since the first few days of this phase, but in the cortex the amount of myelination is still very slight.
The third phase begins at the twentieth day after birth and lasts to the ninetieth day after birth when the rapid growth of body decreases. During and after this phase the cortical thickness remains almost fixed, despite the increase in brain weight or brain size. Rapid myelination of the cortical fibers first appears at the beginning of this phase and is also present in the corpus striatum or in other central nuclei. Thus the increase in brain mass during this phase is due principally to the deposition of the myelin sheaths. The fact that the cortex has reached its full thickness before the rapid development in myelination begins, leads us to conclude that the formation of the myelin sheath on any axon does not begin until the axon has established functional connections with one or more other neurons. During subsequent growth, both the axon and its myelin sheath lengthen and enlarge without disturbing their relative volume relations. It appears that the very considerable increases in the area of the cortex, after its thickness is attained, is accomplished largely by the formation of the myelin sheaths.
X. Summary
1. The postnatal increase in the thickness of the cerebral cortex according to body growth has been systematically investigated, employing as material 96 male and 28 female albino rats, representing every stage of postnatal life.
2. The material was fixed, imbedded and stained by a uniform technique devised for the present investigation. The cortical thickness was measured on sagittal, frontal and horizontal sections, 10 micra thick, all of which were taken from the fixed levels of the brain. Two brains were required for the three sections. On these sections, thirteen localities in all were measured. These localities were accurately determined and represent regions well distributed over the surface of hemisphere. The values thus obtained from the measurements on the slide were later converted into the actual thickness of the cortex in fresh condition, by the use of correction-coefficients based on observation. This series of determinations is the first we have on the cortex of any mammal, which aims to represent the thickness of the cortex when fresh.
3. The data are presented in tables and in charts. The cortical cell-lamination of the albino rat is critically reviewed, and the characteristic appearance of the cortex in the newborn is described.
4. The cortex at the frontal pole of the hemisphere is the thickest and that at the occipital pole is the thinnest. Speaking in general terms, the cortex diminishes in thickness from the frontal to the occipital pole and from the dorsal to the ventral aspect.
5. The cerebral cortex of a newborn rat is somewhat less mature than the cortex of man at birth. In the newborn rat, the general average thickness of the cortex is 0.74 mm., corresponding to a brain weight of 0.25 gram.
6. After birth, the general average of the cortical thickness increases very rapidly during the first ten days, thickening to 1.73 mm., or more than twice the thickness at birth, while the brain weight increases to 0.95 gram during the same phase. This is designated by me as the first phase of the cortical development in the albino rat in its postnatal life.
7. Between the tenth day and twentieth day after birth, the cortical thickness increases more slowly, attaining at twenty days to within 4 per cent of the full thickness of the cortex, namely 1.84 mm., or about 2.5 times the thickness at birth, while the brain weight increases to 1.15 grams. This is designated the second phase of the cortical development in the albino rat.
8. From the twentieth to the ninetieth day, the cortical thickness increases but little on the average, attaining at about 90 days the thickness of 1.93 mm. or 2.6 times the thickness at birth, while the brain weight has increased to about 1.80 grams. This is designated the tliird phase of the cortical development in the albino rat.
After the ninetieth day, there is no significant change in the thickness of the cortex, but the area of the cortex increases as the brain weight rises towards two grams.
9. On comparing the rate of increase in the cortical thickness during the three phases, we find that during the first phase the average daily increase is 62 times and in the second phase 7 times as rapid as in the third phase (table 13). This corresponds well with the rate of mitosis in the cerebrum and cell immigration in each phase. Furthermore if the ratio of the increase of cortical thickness is compared with that of the increase of one diameter of the brain, the former is much greater than the latter in the first phase, almost equal in the second phase, and much less in the third phase. It appears, therefore, that in the first phase the cortex increases its thickness by receiving newly formed cells from the matrix and at the same time by the enlargement of the cell bodies; in the second phase, however, mainly by the enlargement of the cell bodies and the growth of the axons and dendrites; while in the third phase it almost ceases to thicken, but extends in area as the result of the formation of the myelin sheaths.
10. On comparing the rapidity of growth in the several localities of the hemisphere, it is easily seen that the cortex at the frontal pole increases its thickness very rapidly and continuously, even after the end of the second phase, while at all the other localities the cortex thickens by similar steps, so that at the end of the second phase all the localities reach nearly the full thickness. The localities heterogeneous in their cell-lamination show some deviation in their courses of thickening from the localities which are typical.
11. If the brain weight is taken as the standard of comparison, no sex difference is to be detected in the cortical thickness.
12. We conclude that the cortex generally attains nearly its full thickness before myelination in the cortex, as shown by the Weigert staining method, has begun.
13. The cortex has nearly its mature thickness at 20 days, just before the young rat is weaned. The growth of the cortex in thickness is therefore precocious.
14. If the relative growth rates of the rat and man are as 30 to 1 (Donaldson 'C8), and the development of the human brain at birth coincides with that of the rat at five days of age, then at about the age of fifteen months the human cortex should have attained nearly its full thickness.
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