Regional quantification of developing human cortical shape with a three-dimensional surface-based magnetic resonance imaging analysis in utero

Although regional differences in cerebral volume have been revealed in developing human brains, little is known regarding the regionalization of cortical shape. This study documented the regional and quantitative shape difference of cortical surfaces for in utero normal fetal brains over a time period essential for the formation of primary cortical folding (22–33 weeks). Each brain surface with complete three‐dimensional morphology was manually extracted from the reconstructed image, which combined surface information from three orthogonal magnetic resonance images in utero. An innovative parcellation was used to dissect the fetal brains into frontal, parietal, temporal and occipital lobes, and to avoid the determination of non‐existent and immature sulci for young fetuses. Distinct cortical shapes were encoded by the shape index automatically. The results of this study show faster shape changes in the occipital lobe than in other regions. Both regional and global shape patterns show that the gyral surface smoothens, whereas the sulcal surface becomes more angular, with gestational age. In addition, the smoothing of gyri is related mainly to the changes in shape of gyral crowns. This study presents the regional differences in early gyrification from the novel aspect of shape. The results of shape pattern analysis for normal fetuses may act as a reference in assessments of prenatal brain pathology and in extensive comparisons between various life stages.     

Brain gyrification in wild and domestic canids: Has domestication changed the gyrification index in domestic dogs?

Over the last 15 years, research on canid cognition has revealed that domestic dogs possess a surprising array of complex sociocognitive skills pointing to the possibility that the domestication process might have uniquely altered their brains; however, we know very little about how evolutionary processes (natural or artificial) might have modified underlying neural structure to support species-specific behaviors. Evaluating the degree of cortical folding (i.e., gyrification) within canids may prove useful, as this parameter is linked to functional variation of the cerebral cortex. Using quantitative magnetic resonance imaging to investigate the impact of domestication on the canine cortical surface, we compared the gyrification index (GI) in 19 carnivore species, including six wild canid and 13 domestic dog individuals. We also explored correlations between global and local GI with brain mass, cortical thickness, white and gray matter volume and surface area. Our results indicated that GI values for domestic dogs are largely consistent with what would be expected for a canid of their given brain mass, although more variable than that observed in wild canids. We also found that GI in canids is positively correlated with cortical surface area, cortical thickness and total cortical gray matter volumes. While we found no evidence of global differences in GI between domestic and wild canids, certain regional differences in gyrification were observed.     

Altered cortical gyrification patterns in panic disorder: Deficits and potential compensation

Abnormal gyrification patterns may reflect aberrant cortical connectivity during an early period of brain maturation. We here investigated anatomical distribution of cortical gyrification deficits underlying panic disorder and the relationships of these potential neurodevelopmental markers with panic symptom severity. High-resolution three-dimensional T1-weighted structural images were obtained from 23 patients with panic disorder and 33 matched healthy individuals. Local gyrification indices were measured in each genetically-based parcellated cortical subregion and regional gyrification patterns were compared between groups. Cortical areas in which gyrification patterns were associated with panic symptom severity were also determined. Significant reductions in cortical gyrification were observed in panic patients compared with healthy individuals, which were mainly distributed in the lateral brain extending from the fronto-parietal to the temporal areas. In contrast, hyper-gyrification in the posteromedial cortical regions which exert interconnecting roles in the default mode network, was associated with less severe panic symptoms. Post-hoc analysis for the inter-regional covariance of local gyrification indices revealed that interconnections of the posteromedial cortical regions with other cortical areas which belong to the default mode network were reduced in panic patients with severe symptoms relative to either less severe patients or healthy individuals. Our findings suggest not only substantial perturbation in cortical gyrification patterns in panic disorder but also potential contribution of integrated cortical folding pattern of the default mode network to alleviated panic severity.     

Cerebral cortical gyrification: a preliminary investigation in temporal lobe epilepsy

PURPOSE: To introduce a measure of global cortical folding in epilepsy by using stereology. Subtle developmental abnormalities associated with temporal lobe epilepsy may encompass brain morphologic changes such as an aberrant degree of cortical folding. METHODS: Stereologic methods of volume and surface-area estimation were applied to in vivo MR brain-image data of a cohort of 20 temporal lobe epilepsy (TLE) patients (10 men, 10 women), and 20 neurologically normal controls (10 men, 10 women). Indices of cerebral gyrification and cerebral atrophy were generated. The impact of side of seizure onset, age at onset, history of febrile seizures, presence or absence of lesions, and presence or absence of secondarily generalized seizures on cerebral gyrification was assessed. RESULTS: Although no significant group mean difference was found in the degree of cerebral gyrification between patients and controls, five of 10 of male patients had an abnormal gyrification when compared with male controls. One female patient had a significant change in gyrification compared with female controls. In general, patients with TLE demonstrated a significant degree of global cerebral atrophy compared with controls. Clinical factors were not demonstrated to affect significantly any of the quantitative parameters. CONCLUSIONS: The results of this study suggest that an aberrant degree of global cerebral gyrification may occur in certain clinical groups of TLE patients. These findings have implications for general theories of developmental susceptibility in TLE.     

Gyrification in the cerebral cortex of primates

The degree of cortical folding in primates has been analyzed using a gyrification index (GI). Correlation analyses of the GI with body weight, brain weight and neopallial volume show that the human data fit the general trend of the nonhuman anthropoids. Bigger primate brains exhibit a higher degree of fissurization, but a taxonomic difference that is independent of brain weight between prosimians and anthropoids has also been observed. In these regressions, anthropoids differed from prosimians by having a larger increase in gyrification for every unit increase in body or brain weight or neopallial volume. A stepwise regression also shows a prosimian-anthropoid difference. The best predictor for convolutedness in anthropoids is neocortical volume, while in prosimians it is brain weight. The GI in catarrhines is correlated with total sulcal length but not number of sulci. This result suggests paleontological studies of total sulcal length can give direct information on the evolution of cortical folding in primates.     

Reduced brain size and gyrification in the brains of dyslexic patients

Dyslexia is a specific learning disability that affects the way in which a person acquires reading skills. The pathologic substrate of the condition has been debated in the literature. Conclusions from postmortem studies remain controversial because series have been based on few and often ill-characterized cases. The present article expands on one of the reported neuropathologic findings in dyslexia, that is, wider minicolumns. Measurements were made of magnetic resonance images in a series of 16 dyslexic and 14 age- and sex-matched controls. Dyslexic patients had significantly smaller total cerebral volume (P = .014) and reduced gyrification index (P = .021). No changes were noted in cortical thickness, the ratio of gray to white matter, or the cross-sectional areas of the corpus callosum and medulla oblongata. The findings, although not conclusive, are in keeping with a minicolumnar defect in dyslexia. The decreased gyrification and preserved cortical thickness can alter the information processing capacity of the brain by providing a greater degree of cortical integration at the expense of a slower response time. The article also emphasizes the contrast between findings in dyslexia and in autism.     

Aberrant cortical gyrification in schizophrenia: a surface-based morphometry study

Background: Schizophrenia is considered to be a disorder of cerebral connectivity associated with disturbances of cortical development. Disturbances in connectivity at an early period of cortical maturation can result in widespread defects in gyrification. Investigating the anatomic distribution of gyrification defects can provide important information about neurodevelopment in patients with schizophrenia. Methods: We undertook an automated surface-based morphometric assessment of gyrification on 3-dimensionally reconstructed cortical surfaces across multiple vertices that cover the entire cortex. We used a sample from our previous research of 57 patients (50 men) with schizophrenia and 41 controls (39 men) in whom we had tested a specific hypothesis regarding presence of both hypo and hypergyria in the prefrontal cortex using a frontal region-of-interest approach. Results: Regions with significant reductions in gyrification (hypogyria) were seen predominantly in the left hemisphere, involving the insula and several regions of the multimodal association cortex. Although the prefrontal hypergyria documented earlier did not survive the statistical correction required for a whole brain search (cluster inclusion at p = 0.0001), significant hypergyric frontal clusters emerged when the threshold was lowered (cluster inclusion at p = 0.05). In the insula, a reduction in gyrification was related to reduced cortical thickness in patients with schizophrenia. Limitations: We studied a sample of patients taking antipsychotic medications, which could have confounded the results. Our sample was predominantly male, limiting the generalizability of our findings. Conclusion: Our observations suggest that the disturbances in cortical gyrification seen in patients with schizophrenia might be related to a disrupted interaction between the paralimbic and the multimodal association cortex and thus might contribute to the pathogenesis of the illness.     

Reduced cortical folding in schizophrenia: an MRI morphometric study

OBJECTIVE: Although well documented, regional brain structural abnormalities in schizophrenia are nonspecific, and morphometric parameters show significant overlapping between patients and healthy comparison subjects. An increasing number of studies have focused on supraregional models involving abnormalities of the neuronal circuitry between cortical regions in schizophrenia. The aim of the present study was to investigate cortical folding as an index of the neuronal wiring in different subtypes of schizophrenia. METHOD: Magnetic resonance imaging measures of gyrification index in intervals of 3.6 mm along the total cerebral cortex were compared in 40 patients with DSM-IV schizophrenia and 20 healthy subjects. Psychopathology was assessed with the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, and the Negative Symptom Rating Scale. RESULTS: The schizophrenia patients showed significantly reduced bilateral cortical folding relative to healthy comparison subjects. Such reductions were more pronounced in those with the disorganized subtype and showed an inverse correlation with negative symptoms and a positive correlation with positive symptoms. The paranoid subtype showed reduced cortical folding that was restricted to the left hemisphere. CONCLUSIONS: These results from a larger patient group confirm a previous report of reduced cortical folding in schizophrenia patients. They also suggest a distinct pattern of abnormality between schizophrenia subtypes regarding the process of cerebral lateralization and are in agreement with the neurodevelopmental hypothesis of schizophrenia.     

Regional brain morphometry and lissencephaly in the Sirenia

Neuroanatomical structure was examined in the brains of West Indian manatees (Trichechus manatus) using computer-based morphometric methods. Although manatees have a small relative brain size, volume estimates of the major brain regions indicate that the telencephalon comprises 71% of total brain volume and is 90% cerebral cortex. These values are comparable to those seen among a diversity of taxa having large relative brain size, including many primates. Manatee brains also exhibit well-defined cortical lamination. The measured gyration index (an index of cortical folding) was 1.06, representing a highly lissencephalic condition. These findings demonstrate that small relative brain size and lissencephaly do not constrain the elaboration of internal brain structures. The marked lissencephalic condition is unusual for brains of this absolute size range, and may be related to the thickness of the cortical gray matter and underlying white matter.     

Gyrification,cortical and subcortical morphometry in neurofibromatosis type 1: an uneven profile of developmental abnormalities

Background

Neurofibromatosis type 1 (NF1) is a monogenic disorder associated with cognitive impairments. In order to understand how mutations in the NF1 gene impact brain structure it is essential to characterize in detail the brain structural abnormalities in patients with NF1. Previous studies have reported contradictory findings and have focused only on volumetric measurements. Here, we investigated the volumes of subcortical structures and the composite dimensions of the cortex through analysis of cortical volume, cortical thickness, cortical surface area and gyrification.

Methods

We studied 14 children with NF1 and 14 typically developing children matched for age, gender, IQ and right/left-handedness. Regional subcortical volumes and cortical gyral measurements were obtained using the FreeSurfer software. Between-group differences were evaluated while controlling for the increase in total intracranial volume observed in NF1.

Results

Subcortical analysis revealed disproportionately larger thalami, right caudate and middle corpus callosum in patients with NF1. Cortical analyses on volume, thickness and surface area were however not indicative of significant alterations in patients. Interestingly, patients with NF1 had significantly lower gyrification indices than typically developing children primarily in the frontal and temporal lobes, but also affecting the insula, cingulate cortex, parietal and occipital regions.

Conclusions

The neuroanatomic abnormalities observed were localized to specific brain regions, indicating that particular areas might constitute selective targets for NF1 gene mutations. Furthermore, the lower gyrification indices were accompanied by a disproportionate increase in brain size without the corresponding increase in folding in patients with NF1. Taken together these findings suggest that specific neurodevelopmental processes, such as gyrification, are more vulnerable to NF1 dysfunction than others. The identified changes in brain organization are consistent with the patterns of cognitive dysfunction in the NF1 phenotype.     

Gyrification abnormalities in childhood- and adolescent-onset schizophrenia.

BACKGROUND: Gyrification is an important index of brain development. We used magnetic resonance scanning technology to compare brain surface morphology and measures of gyrification in children and adolescents with a schizophrenia spectrum disorder and in age-equivalent healthy controls. METHODS: Magnetic resonance scans were obtained from 42 patients and 24 healthy controls, mean age 17.7 years for both groups. We employed novel quantitative measures of brain morphology, including cortical thickness and a variety of indices of sulcal and gyral curvature. We examined these measures in the whole brain and in the frontal, temporal, parietal, and occipital lobes. RESULTS: There were significant decreases in cortical thickness in the patients. This was most pronounced in the cortical tissue that underlies the sulci. The patient group had significantly more flattened curvature in the sulci and more steeped or peaked curvature in the gyri. CONCLUSIONS: This study quantitatively examines cortical thickness and surface morphology in children and adolescents with schizophrenia. Patients with schizophrenia demonstrated patterns of brain morphology that were distinctly different from healthy controls. In light of current theories of the formation of gyri and sulci, these changes may reflect aberrations in cerebral and subcortical connectivity.     

Development of cortical and subcortical brain structures in childhood and adolescence: a structural MRI study

The purpose of the present study was to describe in greater anatomical detail the changes in brain structure that occur during maturation between childhood and adolescence. High-resolution MRI, tissue classification, and anatomical segmentation of cortical and subcortical regions were used in a sample of 35 normally developing children and adolescents between 7 and 16 years of age (mean age 11 years; 20 males, 15 females). Each cortical and subcortical measure was examined for age and sex effects on raw volumes and on the measures as proportions of total supratentorial cranial volume. Results indicate age-related increases in total supratentorial cranial volume and raw and proportional increases in total cerebral white matter. Gray-matter volume reductions were only observed once variance in total brain size was proportionally controlled. The change in total cerebral white-matter proportion was significantly greater than the change in total cerebral gray-matter proportion over this age range, suggesting that the relative gray-matter reduction is probably due to significant increases in white matter. Total raw cerebral CSF volume increases were also observed. Within the cerebrum, regional patterns varied depending on the tissue (or CSF) assessed. Only frontal and parietal cortices showed changes in gray matter, white matter, and CSF measures. Once the approximately 7% larger brain volume in males was controlled, only mesial temporal cortex, caudate, thalamus, and basomesial diencephalic structures showed sex effects with the females having greater relative volumes in these regions than the males. Overall, these results are consistent with earlier reports and describe in greater detail the regional pattern of age-related differences in gray and white matter in normally developing children and adolescents.     

A functional polymorphism of the brain derived neurotrophic factor gene and cortical anatomy in autism spectrum disorder

Autism Spectrum Disorder (ASD) is associated with both (i) post-mortem and neuroimaging evidence of abnormal cortical development, and (ii) altered signalling in Brain Derived Neurotrophic Factor (BDNF) pathways - which regulate neuroproliferative and neuroplastic processes. In healthy controls genotype at a single nucleotide polymorphism that alters BDNF signalling (Val66met) has been related to regional cortical volume. It is not known however if this influence on brain development is intact in ASD. Therefore we compared the relationship between genotype and cortical anatomy (as measured using in vivo Magnetic Resonance Imaging) in 41 people with ASD and 30 healthy controls. We measured cortical volume, and its two sole determinants - cortical thickness and surface area - which reflect differing neurodevelopmental processes. We found "Group-by-Genotype" interactions for cortical volume in medial (caudal anterior cingulate, posterior cingulate) and lateral (rostral middle, lateral orbitofrontal, pars orbitalis and pars triangularis) frontal cortices. Furthermore, within (only) these regions "Group-by-Genotype" interactions were also found for surface area. No effects were found for cortical thickness in any region. Our preliminary findings suggest that people with ASD have differences from controls in the relationship between BDNF val66met genotype and regional (especially frontal) cortical volume and surface area, but not cortical thickness. Therefore alterations in the relationship between BDNF val66met genotype and surface area in ASD may drive the findings for volume. If correct, this suggests ASD is associated with a distorted relationship between BDNF val66met genotype and the determinants of regional cortical surface area - gyrification and/or sulcal positioning.     

Sex-dependent effects of schizophrenia: an MRI study of gyral folding, and cortical and white matter volume

Alterations, sometimes sex-dependent, in volumes and gyral structure of areas of cerebral cortex have been reported in schizophrenia. Such changes imply an anomaly of connectivity. The gyrification, percentage of tissue volume attributed to white matter, cortical volume and white matter volume were measured from magnetic resonance images in males and females with (n = 61) and without (n = 42) schizophrenia. The frontal, temporal and an amalgam of occipital and parietal lobes were examined in both hemispheres. There was no effect of schizophrenia on the gyrification of the brain. For the volume of occipito-parietal white matter, females with schizophrenia had bilaterally lower volumes, while males with schizophrenia had greater volumes than controls. It is concluded that the changes in connectivity underlying the pathogenesis of schizophrenia are sex-specific and expressed in occipito-parietal white matter.     

Diagnostic Discontinuity in Psychosis: A Combined Study of Cortical Gyrification and Functional Connectivity

The point of rarity in brain structure and function that separates the 2 major psychotic disorders—schizophrenia and bipolar disorder—is presently unknown. The aim of this study is to combine surface anatomical and functional imaging modalities to quantify the integrity of cortical connectivity in pursuit of the neural basis of the Kraepelinian “line of divide.” We tested the hypothesis that multimodal brain regions show overlapping abnormalities in both disorders, while schizophrenia-specific defects are likely to be localized to sensory processing regions. Cortical folding patterns (gyrification) and functional connectivity hub architecture (degree centrality) were studied in a sample of 39 subjects with established schizophrenia, 20 subjects with psychotic bipolar disorder, and 34 healthy controls. We observed a significant difference between the 2 groups in both gyrification and functional connectivity of the visual processing regions. Further, the aberrant functional connectivity of the visual processing regions predicted persistent symptom burden better than the diagnostic information. Using a spatial similarity analysis, we observed that the degree of overlap between the 2 disorders was small (25%) for changes in cortical gyrification and modest (51%) for changes in functional connectivity measured during a cognitive task (n-back). In conclusion, our results suggest that prominent unimodal sensory processing deficits are more likely to be present in schizophrenia than in bipolar disorder. Further, connectivity-based neuroimaging measures appear to be better indicators of diagnostic discontinuity than the symptom-based clinical information.Key words: Kraepelinian, bipolar disorder, visual processing, insula, gyrification, schizophrenia     

Parieto-frontal gyrification and working memory in healthy adults

Gyrification of the cortical mantle is a dynamic process that increases with cortical surface area and decreases with age. Increased gyrification is associated with higher scores on cognitive tasks in adults; however, the degree to which this relationship is independent of cortical surface area remains undefined. This study investigates whether regional variation in gyrification is associated with domain-general and domain-specific cognition. Our hypothesis is that increased local gyrification confers a functional advantage that is independent of surface area. To quantify regional gyrification, we computed the local gyrification index (LGI) at each vertex and averaged across a bilateral parietal-frontal region associated with general intelligence and reasoning (Jung and Haier 2007). A sample of 48 healthy adults (24 males/24 females; ages 18–68 years) completed a high-resolution 3 T T1-weighted MRI and standardized administration of the Wechsler Adult Intelligence Scale (WAIS). We found a positive correlation between cortical gyrification and working memory, which remained significant after controlling for cortical surface area. Results suggest that a higher degree of local cortical folding confers a functional advantage that is independent from surface area and evident for more dynamic or “fluid” cognitive processes (i.e., working memory) rather than over-learned or “crystallized” cognitive processes.     

Assessment of cortical degeneration in patients with Parkinson's disease by voxel-based morphometry, cortical folding, and cortical thickness

Noninvasive brain imaging methods provide useful information on cerebral involution and degenerative processes. Here we assessed cortical degeneration in 20 nondemented patients with Parkinson's disease (PD) and 20 healthy controls using three quantitative neuroanatomical approaches: voxel‐based morphometry (VBM), cortical folding (BrainVisa), and cortical thickness (FreeSurfer). We examined the relationship between global and regional gray matter (GM) volumes, sulcal indices, and thickness measures derived from the previous methods as well as their association with cognitive performance, age, severity of motor symptoms, and disease stage. VBM analyses showed GM volume reductions in the left temporal gyrus in patients compared with controls. Cortical folding measures revealed significant decreases in the left frontal and right collateral sulci in patients. Finally, analysis of cortical thickness showed widespread cortical thinning in right lateral occipital, parietal and left temporal, frontal, and premotor regions. We found that, in patients, all global anatomical measures correlated with age, while GM volume and cortical thickness significantly correlated with disease stage. In controls, a significant association was found between global GM volume and cortical folding with age. Overall these results suggest that the three different methods provide complementary and related information on neurodegenerative changes occurring in PD, however, surface‐based measures of cortical folding and especially cortical thickness seem to be more sensitive than VBM to identify regional GM changes associated to PD. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Localised reductions in gyrification in the posterior cingulate: schizophrenia and controls

Several authors report changes in the volume and degree of cortical folding in several presumptive regions of schizophrenia patients. However, no research, to our knowledge, has looked for schizophrenia related differences in cortical volume and degree of cortical folding in post-mortem posterior cingulate cortex (PCCx). Method: Brain tissues from 9 people who suffered from schizophrenia (DSM-IV) and 9 controls were cut into 3 mm coronal slices. Three alternative PCCx blocks were available for research. The 3 PCCx blocks were cut into 50 microm sections. The volume and gyrification index (GI) were measured in 15 tissue sections per brain (5 sections per block). Results: People who suffered with schizophrenia showed significant reductions in GI in rostral PCCx, trend reductions were seen in medial and caudal PCCx. In addition, the average volume of the rostral tissue sections was significantly lower in the schizophrenia cohort, suggesting that schizophrenia is associated with reduced volume in the rostral PCCx. However, a true volumetric assessment of the whole PCCx, rather than a limited number of sections from three alternative blocks, is needed to confirm such a hypothesis.     

Disturbed gyrification of the prefrontal region in male schizophrenic patients: A morphometric postmortem study

OBJECTIVE: The goal was to test the hypothesis that abnormalities of gyrification are present in the prefrontal region of postmortem brains from schizophrenic patients. METHOD: The authors compared the prefrontal regions in brains from 24 schizophrenic patients and 24 normal comparison subjects. The gyrification index, the ratio of inner and outer surface contours, was measured bilaterally in three different slices from each brain. Area measurements of gray and white matter were studied separately by planimetric analysis in the same sections. In addition, a gray-to-white-matter ratio and an asymmetry coefficient were computed. RESULTS: The mean gyrification index on the right side was significantly higher in the male schizophrenic patients than in the comparison men. The gyrification index of the female patients was not significantly different from that of the female comparison subjects. Analysis of area measurements revealed no significant differences. CONCLUSIONS: As gyrification is an ontogenetic stable feature unaffected by atrophic processes during aging, the gyrification abnormalities of the prefrontal region provide further evidence of the importance of a neurodevelopmental mechanism in the etiology of schizophrenia, at least in males.