ex vivo histological measurements of adult VTC
( 8, 9). Notably, pFus-faces and CoS-places are cyto-architectonically dissociable, where the former
is largely confined to fusiform gyrus cytoarchitectonic area FG2 and the latter to FG3 ( 10).
Using cortex-based alignment ( 11), we generated maximum probability maps (MPMs) of
f ROIs from 20 living adults and cytoarchitectonic regions of interest (cROIs) from 10 postmortem adults and compared them on the
FreeSurfer average brain (supplementary materials and methods). Mirroring previous work
( 10), pFus-faces was largely within FG2, and CoS-places was largely within FG3 (Fig. 3C). Extracting T1 measurements of living adults from the
regions corresponding to the MPM of FG2 and
FG3 showed significantly lower T1 in FG2 compared to FG3 (Fig. 3D).
We compared these T1 measurements from
MPMs of FG2 and FG3 to the volume fraction
of cell bodies across cortical layers of areas FG2
and FG3 measured by the mean gray level index
(GLI) ( 8, 9) from 20-mm histological sections
(supplementary materials and methods). The
mean GLI of FG3 was 12. 73 ± 1.29, which was
significantly larger (pairwise t test, P < 0.05)
than the mean GLI of FG2 ( 11. 65 ± 1.83, Fig.
3D). A smaller GLI in FG2 corresponded to a
larger amount of neuropil, which is the space
surrounding the cell bodies that contains synapses,
dendrites, axons with or without myelin, and glial
and astrocytic processes. Assuming all other conditions were the same, more abundant neuropil
in FG2 would manifest as lower T1 in qMRI.
One neuropil compartment that may develop
is myelin. Increased myelination of axons in deep
cortical layers could push the white-gray matter
boundary into cortex, predicting thinner FG2–
pFus-faces than FG3–CoS-places in adulthood.
Contrary to this prediction, both postmortem
and in vivo FG2 and pFus-faces tended to be
thicker than FG3 and CoS-places (fig. S7, G and
H). Cortical thickness estimates were the same
for cell body and myelin staining of FG2, suggesting that deep cortical layers were likely not
misclassified as white matter in MRI (fig. S7, A
and B). Although FG2 and FG3 were similarly
myelinated in postmortem adults (fig. S7, C to
F), myelin could increase within the cortex across
development. Since myelin volume linearly contributes to MTV and mean MTV in pFus-faces
voxels increased by 12.6% from childhood to
adulthood, we simulated the amount by which
the volume of the myelin sheath would need
to increase in order to account for these observations (supplementary materials and methods).
Simulations using various ranges of axonal radii
and percentages of axons myelinated showed
that the radius of the myelin sheath would need
to increase 2- to 10-fold to account for the development of MTV in pFus-faces (Fig. 3E). We
believe that such an increase is anatomically infeasible because it would result in fibers that are
composed largely of myelin sheath.
Together, the histological measurements and
the simulations suggest that development of T1
in pFus-faces may be driven by microstructural
proliferation in a combination of cortical com-
partments. One such compartment may be den-
drites. Our data are consistent with research in
monkey inferotemporal cortex, which is the pro-
posed homolog of human VTC, where anatom-
ical development is characterized by a prolific
generation of dendritic spines and a doubling
in size of dendritic arbors ( 7). The growth of
dendritic arbors may impact the spatial extent
from which pyramidal neurons pool informa-
tion ( 13, 14) and the spatial extent of lateral
inhibition ( 12), both of which could enhance
functional selectivity. Another source of tissue
development may be developmental increases
in oligodendrocytes and myelination ( 15–17),
which are thought to depend on neural function
( 18). Although myelination is a likely source of
T1 change, simulation results suggest that it is
likely not the only source. Other contributions
to T1 development may arise from changes in
perineuronal iron–protein matrices ( 19) or glial
and astrocytic structural changes observed dur-
ing learning in adults ( 20).
Overall, these data suggest a rethinking of
the anatomical development of cortex throughout childhood. First, we found a differential development of VTC; some regions showed profound
changes, while others remained stable. Second,
we found evidence for microstructural proliferation in the fusiform gyrus during childhood, which implicates a different mechanism
than the pruning that occurs during infant
development ( 6). These findings suggest that
improvements in behavior are a product of an
interplay between structural and functional
changes in cortex.
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Fig. 3. Assessment
of different tissue
(A) Graph shows
of T1 in pFus-faces
(red) and CoS-places
(yellow) in 20 children,
where solid line indicates mean and
shaded region indicates standard error
Violin plot shows mean
T1 of right pFus-faces
and CoS-places in
these children, where
width indicates subject
density, solid line indicates group mean, and dotted lines indicate standard error. (B) Same as (A) for 20 adults. (C) Maximum probability maps (MPMs) of pFus-faces and CoS-places ( 20 adults) and MPMs of cytoarchitectonic areas FG2 and FG3 ( 10 postmortem adults) on the Freesurfer average brain. (D) Left, mean T1 from
the MPMs of FG2 and FG3 in 20 adults. Notation is the same as in (A). Right, mean GLI profiles of FG2 (purple) and FG3 (blue) in 10 postmortem adults.
(E) Simulations of myelin sheath volume increase in a cubic millimeter of cortex to account for development of MTV in pFus-faces if myelin was the sole
factor. The x axis shows axon diameter, colored lines indicate number of axons in a cubic millimeter (see colorbar), example axons, dark gray circles show
initial fiber diameter, and light gray shading shows simulated fiber diameter after development.