Cortical Folding of the Primate Brain: An Interdisciplinary Examination of the Genetic Architecture,Modularity, and Evolvability of a Significant Neurological Trait in Pedigreed Baboons (Genus Papio)

Folding of the primate brain cortex allows for improved neural processing power by increasing cortical surface area for the allocation of neurons. The arrangement of folds (sulci) and ridges (gyri) across the cerebral cortex is thought to reflect the underlying neural network. Gyrification, an adaptive trait with a unique evolutionary history, is affected by genetic factors different from those affecting brain volume. Using a large pedigreed population of ∼1000 Papio baboons, we address critical questions about the genetic architecture of primate brain folding, the interplay between genetics, brain anatomy, development, patterns of cortical–cortical connectivity, and gyrification’s potential for future evolution. Through Mantel testing and cluster analyses, we find that the baboon cortex is quite evolvable, with high integration between the genotype and phenotype. We further find significantly similar partitioning of variation between cortical development, anatomy, and connectivity, supporting the predictions of tension-based models for sulcal development. We identify a significant, moderate degree of genetic control over variation in sulcal length, with gyrus-shape features being more susceptible to environmental effects. Finally, through QTL mapping, we identify novel chromosomal regions affecting variation in brain folding. The most significant QTL contain compelling candidate genes, including gene clusters associated with Williams and Down syndromes. The QTL distribution suggests a complex genetic architecture for gyrification with both polygeny and pleiotropy. Our results provide a solid preliminary characterization of the genetic basis of primate brain folding, a unique and biomedically relevant phenotype with significant implications in primate brain evolution.     

Alterations in Cortical Morphology after Neonatal Stroke: Compensation in the Contralesional Hemisphere?

Although neonatal arterial ischemic stroke is now well‐studied, its complex consequences on long‐term cortical brain development has not yet been solved. In order to understand the brain development after focal early brain lesion, brain morphometry needs to be evaluated using structural parameters. In this work, our aim was to study and analyze the changes in morphometry of ipsi‐ and contralesional hemispheres in seven‐year‐old children following neonatal stroke. Therefore, we used surface‐based morphometry in order to examine the cortical thickness, surface area, cortical volume, and local gyrification index in two groups of children that suffered from neonatal stroke in the left (n = 19) and right hemispheres (n = 15) and a group of healthy controls (n = 30). Reduced cortical thickness, surface area, and cortical volumes were observed in the ipsilesional hemispheres for both groups in comparison with controls. For the group with left‐sided lesions, higher gyrification of the contralesional hemisphere was observed primarily in the occipital region along with higher surface area and cortical volume. As for the group with right‐sided lesions, higher gyrification was detected in two separate clusters also in the occipital lobe of the contralesional hemisphere, without a significant change in cortical thickness, surface area, or cortical volume. This is the first time that alterations of structural parameters are detected in the “healthy” hemisphere after unilateral neonatal stroke indicative of a compensatory phenomenon. Moreover, findings presented in this work suggest that lesion lateralization might have an influence on brain development and maturation.     

Reduced Cortical Complexity in Children with Prader-Willi Syndrome and Its Association with Cognitive Impairment and Developmental Delay

Background

Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group.

Methods

High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite.

Results

Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ.

Conclusions

These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene networks that play a prominent role in early brain development.     

Hemispherically-Unified Surface Maps of Human Cerebral Cortex: Reliability and Hemispheric Asymmetries

Understanding the anatomical and structural organization of the cerebral cortex is facilitated by surface-based analysis enabled by FreeSurfer, Caret, and related tools. Here, we examine the precision of FreeSurfer parcellation of the cortex and introduce a method to align FreeSurfer-registered left and right hemispheres onto a common template in order to characterize hemispheric asymmetries. The results are visualized using Mollweide projections, an area-preserving map. The regional distribution, inter-hemispheric asymmetries and intersubject variability in cortical curvature, sulcal depth, cortical thickness, and cortical surface area of 138 young, right handed subjects were analyzed on the Mollweide projection map of the common spherical space. The results show that gyral and sulcal structures are aligned with high but variable accuracy in different cortical regions and show consistent hemispheric asymmetries that are maximal in posterior temporal regions.     

Cortical gyrification and sulcal spans in early stage Alzheimer's disease

Alzheimer's disease (AD) is characterized by an insidious onset of progressive cerebral atrophy and cognitive decline. Previous research suggests that cortical folding and sulcal width are associated with cognitive function in elderly individuals, and the aim of the present study was to investigate these morphological measures in patients with AD. The sample contained 161 participants, comprising 80 normal controls, 57 patients with very mild AD, and 24 patients with mild AD. From 3D T1-weighted brain scans, automated methods were used to calculate an index of global cortex gyrification and the width of five individual sulci: superior frontal, intra-parietal, superior temporal, central, and Sylvian fissure. We found that global cortex gyrification decreased with increasing severity of AD, and that the width of all individual sulci investigated other than the intra-parietal sulcus was greater in patients with mild AD than in controls. We also found that cognitive functioning, as assessed by Mini-Mental State Examination (MMSE) scores, decreased as global cortex gyrification decreased. MMSE scores also decreased in association with a widening of all individual sulci investigated other than the intra-parietal sulcus. The results suggest that abnormalities of global cortex gyrification and regional sulcal span are characteristic of patients with even very mild AD, and could thus facilitate the early diagnosis of this condition.     

Adolescent Brain Maturation and Cortical Folding: Evidence for Reductions in Gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development.     

Surface Vulnerability of Cerebral Cortex to Major Depressive Disorder

Major depressive disorder (MDD) is accompanied by atypical brain structure. This study first presents the alterations in the cortical surface of patients with MDD using multidimensional structural patterns that reflect different neurodevelopment. Sixteen first-episode, untreated patients with MDD and 16 matched healthy controls underwent a magnetic resonance imaging (MRI) scan. The cortical maps of thickness, surface area, and gyrification were examined using the surface-based morphometry (SBM) approach. Increase of cortical thickness was observed in the right posterior cingulate region and the parietal cortex involving the bilateral inferior, left superior parietal and right paracentral regions, while decreased thickness was noted in the parietal cortex including bilateral pars opercularis and left precentral region, as well as the left rostral-middle frontal regions in patients with MDD. Likewise, increased or decreased surface area was found in five sub-regions of the cingulate gyrus, parietal and frontal cortices (e.g., bilateral inferior parietal and superior frontal regions). In addition, MDD patients exhibited a significant hypergyrification in the right precentral and supramarginal region. This integrated structural assessment of cortical surface suggests that MDD patients have cortical alterations of the frontal, parietal and cingulate regions, indicating a vulnerability to MDD during earlier neurodevelopmental process.     

Mechanical role of a growing solid tumor on cortical folding

Cortical folding, or convolution of the brain, is a vital process in mammals that causes the brain to have a wrinkled appearance. The existence of different types of prenatal solid tumors may alter this complex phenomenon and cause severe brain disorders. Here we interpret the effects of a growing solid tumor on the cortical folding in the fetal brain by virtue of theoretical analyses and computational modeling. The developing fetal brain is modeled as a simple, double-layered, and soft structure with an outer cortex and an inner core, in combination with a circular tumor model imbedded in the structure to investigate the developmental mechanism of cortical convolution. Analytical approaches offer introductory insight into the deformation field and stress distribution of a developing brain. After the onset of instability, analytical approaches fail to capture complex secondary evolution patterns, therefore a series of non-linear finite element simulations are carried out to study the crease formation and the influence from a growing solid tumor inside the structure. Parametric studies show the dependency of the cortical folding pattern on the size, location, and growth speed of a solid tumor in fetal brain. It is noteworthy to mention that there is a critical distance from the cortex/core interface where the growing tumor shows its pronounced effect on the cortical convolution, and that a growing tumor decreases the gyrification index of cortical convolution while its stiffness does not have a profound effect on the gyrification process.     

Cortical Thickness,Surface Area and Subcortical Volume Differentially Contribute to Cognitive Heterogeneity in Parkinson’s Disease

Parkinson’s disease (PD) is often associated with cognitive deficits, although their severity varies considerably between patients. Recently, we used voxel-based morphometry (VBM) to show that individual differences in gray matter (GM) volume relate to cognitive heterogeneity in PD. VBM does, however, not differentiate between cortical thickness (CTh) and surface area (SA), which might be independently affected in PD. We therefore re-analyzed our cohort using the surface-based method FreeSurfer, and investigated (i) CTh, SA, and (sub)cortical GM volume differences between 93 PD patients and 45 matched controls, and (ii) the relation between these structural measures and cognitive performance on six neuropsychological tasks within the PD group. We found cortical thinning in PD patients in the left pericalcarine gyrus, extending to cuneus, precuneus and lingual areas and left inferior parietal cortex, bilateral rostral middle frontal cortex, and right cuneus, and increased cortical surface area in the left pars triangularis. Within the PD group, we found negative correlations between (i) CTh of occipital areas and performance on a verbal memory task, (ii) SA and volume of the frontal cortex and visuospatial memory performance, and, (iii) volume of the right thalamus and scores on two verbal fluency tasks. Our primary findings illustrate that i) CTh and SA are differentially affected in PD, and ii) VBM and FreeSurfer yield non-overlapping results in an identical dataset. We argue that this discrepancy is due to technical differences and the subtlety of the PD-related structural changes.     

The anatomy of the cerebral cortex of the echidna (Tachyglossus aculeatus)

The cerebral cortex of the echidna is notable for its extensive folding and the positioning of major functional areas towards its caudal extremity. The gyrification of the echidna cortex is comparable in magnitude to prosimians and cortical thickness and neuronal density are similar to that seen in rodents and carnivores. On the other hand, many pyramidal neurons in the cerebral cortex of the echidna are atypical with inverted somata and short or branching apical dendrites. All other broad classes of neurons noted in therian cortex are also present in the echidna, suggesting that the major classes of cortical neurons evolved prior to the divergence of proto- and eutherian lineages. Dendritic spine density on dendrites of echidna pyramidal neurons in somatosensory cortex and apical dendrites of motor cortex pyramidal neurons is lower than that found in eutheria. On the other hand, synaptic morphology, density and distribution in somatosensory cortex are similar to that in eutheria. In summary, although the echidna cerebral cortex displays some structural features, which may limit its functional capacities (e.g. lower spine density on pyramidal neurons), in most structural parameters (e.g. gyrification, cortical area and thickness, neuronal density and types, synaptic morphology and density), it is comparable to eutheria.     

Quantifying Agreement between Anatomical and Functional Interhemispheric Correspondences in the Resting Brain

The human brain is composed of two broadly symmetric cerebral hemispheres, with an abundance of reciprocal anatomical connections between homotopic locations. However, to date, studies of hemispheric symmetries have not identified correspondency precisely due to variable cortical folding patterns. Here we present a method to establish accurate correspondency using position on the unfolded cortical surface relative to gyral and sulcal landmarks. The landmark method is shown to outperform the method of reversing standard volume coordinates, and it is used to quantify the functional symmetry in resting fMRI data throughout the cortex. Resting brain activity was found to be maximally correlated with locations less than 1 cm away on the cortical surface from the corresponding anatomical location in nearly half of the cortex. While select locations exhibited asymmetric patterns, precise symmetric relationships were found to be the norm, with fine-grained symmetric functional maps demonstrated in motor, occipital, and inferior frontal cortex.     

Detection of epileptogenic cortical malformations with surface-based MRI morphometry

Magnetic resonance imaging has revolutionized the detection of structural abnormalities in patients with epilepsy. However, many focal abnormalities remain undetected in routine visual inspection. Here we use an automated, surface-based method for quantifying morphometric features related to epileptogenic cortical malformations to detect abnormal cortical thickness and blurred gray-white matter boundaries. Using MRI morphometry at 3T with surface-based spherical averaging techniques that precisely align anatomical structures between individual brains, we compared single patients with known lesions to a large normal control group to detect clusters of abnormal cortical thickness, gray-white matter contrast, local gyrification, sulcal depth, jacobian distance and curvature. To assess the effects of threshold and smoothing on detection sensitivity and specificity, we systematically varied these parameters with different thresholds and smoothing levels. To test the effectiveness of the technique to detect lesions of epileptogenic character, we compared the detected structural abnormalities to expert-tracings, intracranial EEG, pathology and surgical outcome in a homogeneous patient sample. With optimal parameters and by combining thickness and GWC, the surface-based detection method identified 92% of cortical lesions (sensitivity) with few false positives (96% specificity), successfully discriminating patients from controls 94% of the time. The detected structural abnormalities were related to the seizure onset zones, abnormal histology and positive outcome in all surgical patients. However, the method failed to adequately describe lesion extent in most cases. Automated surface-based MRI morphometry, if used with optimized parameters, may be a valuable additional clinical tool to improve the detection of subtle or previously occult malformations and therefore could improve identification of patients with intractable focal epilepsy who may benefit from surgery.     

Automated Sulcal Depth Measurement on Cortical Surface Reflecting Geometrical Properties of Sulci

Sulcal depth that is one of the quantitative measures of cerebral cortex has been widely used as an important marker for brain morphological studies. Several studies have employed Euclidean (EUD) or geodesic (GED) algorithms to measure sulcal depth, which have limitations that ignore sulcal geometry in highly convoluted regions and result in under or overestimated depth. In this study, we proposed an automated measurement for sulcal depth on cortical surface reflecting geometrical properties of sulci, which named the adaptive distance transform (ADT). We first defined the volume region of cerebrospinal fluid between the 3D convex hull and the cortical surface, and constructed local coordinates for that restricted region. Dijkstra’s algorithm was then used to compute the shortest paths from the convex hull to the vertices of the cortical surface based on the local coordinates, which may be the most proper approach for defining sulcal depth. We applied our algorithm to both a clinical dataset including patients with mild Alzheimer’s disease (AD) and 25 normal controls and a simulated dataset whose shape was similar to a single sulcus. The mean sulcal depth in the mild AD group was significantly lower than controls (p = 0.007, normal [mean±SD]: 7.29±0.23 mm, AD: 7.11±0.29) and the area under the receiver operating characteristic curve was relatively high, showing the value of 0.818. Results from clinical dataset that were consistent with former studies using EUD or GED demonstrated that ADT was sensitive to cortical atrophy. The robustness against inter-individual variability of ADT was highlighted through simulation dataset. ADT showed a low and constant normalized difference between the depth of the simulated data and the calculated depth, whereas EUD and GED had high and variable differences. We suggest that ADT is more robust than EUD or GED and might be a useful alternative algorithm for measuring sulcal depth.     

Orientation tuning--a crooked path to the straight and narrow

Neurons in visual cortex are selective for the orientation of a visual stimulus, while the receptive fields of their thalamic input are circular. Cortical orientation selectivity arises from the organization of both thalamic input and local cortical circuits. In this issue of Neuron, Schummers and colleagues provide evidence that the local circuit mechanisms contributing to orientation selectivity differ depending on the local organization of the orientation map.     

Developmental mechanisms of gyrification

Folding of the cerebral cortex is a fundamental milestone of mammalian brain evolution associated with dramatic increases in size and complexity. Cortex folding takes place during embryonic and perinatal development and is important to optimize the functional organization and wiring of the brain, while allowing fitting a large cortex in a limited cranial volume. Cortex growth and folding are the result of complex cellular and mechanical processes that involve neural stem progenitor cells and their lineages, the migration and differentiation of neurons, and the genetic programs that regulate and fine-tune these processes. Here, we provide an updated overview of the most significant and recent advances in our understanding of developmental mechanisms regulating cortical gyrification.     

Cortical neurons projecting to the posterior part of the superior temporal sulcus with particular reference to the posterior association area. An HRP study in the monkey

Corticocortical connections from the posterior association area to the posterior part of the superior temporal sulcal cortex (STs area) were studied in the monkey by means of retrograde axonal transport of horseradish peroxidase (HRP) or wheatgerm-agglutinin-conjugated HRP (WGA-HRP). After injecting 0.05-0.2 microliter of 50% HRP or 5% WGA-HRP into the STs area, labeled cells were examined in various cortical regions. The dorsal wall of the STs receives fibers mainly from the inferior parietal lobule (area 7) and superior temporal gyrus (area 22), whereas the ventral wall and floor part of the STs receive fibers from the posterior inferotemporal gyrus (area TEO) and prestriate cortex (areas 18 and 19). The deeper parts of the dorsal wall close to the floor region of the STs area also receive many fibers from the cortical walls surrounding the intraparietal, lunate and lateral sulci. Both the dorsal and ventral cortical walls of the intraparietal sulcus send fibers mainly to the deep dorsal wall of the STs. The ventral wall of the STs, on the other hand, receives fibers only from the ventral wall of the intraparietal sulcus. The medial surface of the prestriate cortex and the parahippocampal region send fibers to both walls of the STs. In the prestriate-STs projections originating from areas around the parieto-occipital sulcus, a topographic correlation is present; area 19 located anterior to the sulcus projects to the dorsal wall, whereas area 18 situated posterior to the sulcus projects to the ventral wall. Only the dorsal wall receives fibers from the cingulate (areas 23 and 24) and subparietal gyri (area 7). The deeper part of the dorsal wall and the ventral wall of the posterior STs area are interconnected with each other, while the upper part of the dorsal wall does not appear to receive fibers from the ventral wall.     

PEA15 loss of function and defective cerebral development in the domestic cat

Cerebral cortical size and organization are critical features of neurodevelopment and human evolution, for which genetic investigation in model organisms can provide insight into developmental mechanisms and the causes of cerebral malformations. However, some abnormalities in cerebral cortical proliferation and folding are challenging to study in laboratory mice due to the absence of gyri and sulci in rodents. We report an autosomal recessive allele in domestic cats associated with impaired cerebral cortical expansion and folding, giving rise to a smooth, lissencephalic brain, and that appears to be caused by homozygosity for a frameshift in PEA15 (phosphoprotein expressed in astrocytes-15). Notably, previous studies of a Pea15 targeted mutation in mice did not reveal structural brain abnormalities. Affected cats, however, present with a non-progressive hypermetric gait and tremors, develop dissociative behavioral defects and aggression with age, and exhibit profound malformation of the cerebrum, with a 45% average decrease in overall brain weight, and reduction or absence of the ectosylvian, sylvian and anterior cingulate gyrus. Histologically, the cerebral cortical layers are disorganized, there is substantial loss of white matter in tracts such as the corona radiata and internal capsule, but the cerebellum is relatively spared. RNA-seq and immunohistochemical analysis reveal astrocytosis. Fibroblasts cultured from affected cats exhibit increased TNFα-mediated apoptosis, and increased FGFb-induced proliferation, consistent with previous studies implicating PEA15 as an intracellular adapter protein, and suggesting an underlying pathophysiology in which increased death of neurons accompanied by increased proliferation of astrocytes gives rise to abnormal organization of neuronal layers and loss of white matter. Taken together, our work points to a new role for PEA15 in development of a complex cerebral cortex that is only apparent in gyrencephalic species.

SummaryGyrification is the neurodevelopmental process in certain mammalian species during which the cerebral cortex expands and folds resulting in the classic wrinkled appearance of the brain. Abnormalities in this process underlie many congenital malformations of the brain. However, unlike many other human malformations, genetic insight into gyrification is not possible in laboratory mice because rodents have a lissencephalic or smooth cerebral cortex. We identified a pathogenic variant in domestic cats that likely causes failure of the cerebral cortex to expand and fold properly, and discovered that the pathogenic variant impairs production of a protein, PEA15 (phosphoprotein expressed in astrocytes-15), involved in intracellular signaling. Affected cats have profound abnormalities in brain development, with minimal changes in their superficial behavior and neurologic function. Additional studies of tissue and cultured cells from affected animals suggest a pathophysiologic mechanism in which increased death of neurons accompanied by increased cell division of astrocytes gives rise to abnormal organization of neuronal layers and loss of white matter. These results provide new insight into a developmental process that is unique to animals with gyrencephalic brains.     

A new method to measure cortical growth in the developing brain

Folding of the cerebral cortex is a critical phase of brain development in higher mammals but the biomechanics of folding remain incompletely understood. During folding, the growth of the cortical surface is heterogeneous and anisotropic. We developed and applied a new technique to measure spatial and directional variations in surface growth from longitudinal magnetic resonance imaging (MRI) studies of a single animal or human subject. MRI provides high resolution 3D image volumes of the brain at different stages of development. Surface representations of the cerebral cortex are obtained by segmentation of these volumes. Estimation of local surface growth between two times requires establishment of a point-to-point correspondence ("registration") between surfaces measured at those times. Here we present a novel approach for the registration of two surfaces in which an energy function is minimized by solving a partial differential equation on a spherical surface. The energy function includes a strain-energy term due to distortion and an "error energy" term due to mismatch between surface features. This algorithm, implemented with the finite element method, brings surface features into approximate alignment while minimizing deformation in regions without explicit matching criteria. The method was validated by application to three simulated test cases and applied to characterize growth of the ferret cortex during folding. Cortical surfaces were created from MRI data acquired in vivo at 14 days, 21 days, and 28 days of life. Deformation gradient and Lagrangian strain tensors describe the kinematics of growth over this interval. These quantitative results illuminate the spatial, temporal, and directional patterns of growth during cortical folding.     

Surface-Based Analyses of Anatomical Properties of the Visual Cortex in Macular Degeneration

Introduction

Macular degeneration (MD) can cause a central visual field defect. In a previous study, we found volumetric reductions along the entire visual pathways of MD patients, possibly indicating degeneration of inactive neuronal tissue. This may have important implications. In particular, new therapeutic strategies to restore retinal function rely on intact visual pathways and cortex to reestablish visual function. Here we reanalyze the data of our previous study using surface-based morphometry (SBM) rather than voxel-based morphometry (VBM). This can help determine the robustness of the findings and will lead to a better understanding of the nature of neuroanatomical changes associated with MD.

Methods

The metrics of interest were acquired by performing SBM analysis on T1-weighted MRI data acquired from 113 subjects: patients with juvenile MD (JMD; n = 34), patients with age-related MD (AMD; n = 24) and healthy age-matched controls (HC; n = 55).

Results

Relative to age-matched controls, JMD patients showed a thinner cortex, a smaller cortical surface area and a lower grey matter volume in V1 and V2, while AMD patients showed thinning of the cortex in V2. Neither patient group showed a significant difference in mean curvature of the visual cortex.

Discussion

The thinner cortex, smaller surface area and lower grey matter volume in the visual cortex of JMD patients are consistent with our previous results showing a volumetric reduction in their visual cortex. Finding comparable results using two rather different analysis techniques suggests the presence of marked cortical degeneration in the JMD patients. In the AMD patients, we found a thinner cortex in V2 but not in V1. In contrast to our previous VBM analysis, SBM revealed no volumetric reductions of the visual cortex. This suggests that the cortical changes in AMD patients are relatively subtle, as they apparently can be missed by one of the methods.