Differential Effects of Fingolimod and Natalizumab on Magnetic Resonance Imaging Measures in Relapsing-Remitting Multiple Sclerosis.

Fingolimod and natalizumab are approved disease-modifying drugs in relapsing-remitting multiple sclerosis (RRMS). The two drugs have different modes of action and may therefore influence different aspects of MS-related tissue damage. In this retrospective cohort study, we longitudinally compared patients treated with fingolimod and patients treated with natalizumab by measures based on structural magnetic resonance imaging (MRI). We included patients with RRMS given that two standardized MRI scans under the same drug were available with an interval of at least 6 months both from therapy start to baseline scan and from baseline scan to follow-up scan. After matching for age, baseline and follow-up scans from 93 patients (fingolimod, 48; natalizumab, 45) were investigated. Mean follow-up time was 1.9 years. We determined the number of new white matter lesions as well as thalamic, cortical, and whole-brain atrophy. After scaling for time of the interscan interval, measures were analyzed by group comparisons and, to account for demographic and clinical characteristics, by multiple regression models and a binary logistic regression model. Compared to natalizumab, fingolimod treatment went along with more new white matter lesions (median [interquartile range, IQR] 0.0 [0.0; 0.7] vs. 0.0 [0.0; 0.0] /year; p < 0.01) whereas whole-brain atrophy was lower (median [IQR] 0.2 [0.0; 0.5] vs. 0.5 [0.2; 1.0] %/year; p = 0.01). These significant differences were confirmed by multiple regression models and the binary logistic regression model. In conclusion, our observation is compatible with stronger neuroprotective properties of fingolimod compared to natalizumab.

In vivo biomarkers of structural and functional brain development and aging in humans.

Brain aging is a major determinant of aging. Along with the aging population, prevalence of neurodegenerative diseases is increasing, therewith placing economic and social burden on individuals and society. Individual rates of brain aging are shaped by genetics, epigenetics, and prenatal environmental. Biomarkers of biological brain aging are needed to predict individual trajectories of aging and the risk for age-associated neurological impairments for developing early preventive and interventional measures. We review current advances of in vivo biomarkers predicting individual brain age. Telomere length and epigenetic clock, two important biomarkers that are closely related to the mechanistic aging process, have only poor deterministic and predictive accuracy regarding individual brain aging due to their high intra- and interindividual variability. Phenotype-related biomarkers of global cognitive function and brain structure provide a much closer correlation to age at the individual level. During fetal and perinatal life, autonomic activity is a unique functional marker of brain development. The cognitive and structural biomarkers also boast high diagnostic specificity for determining individual risks for neurodegenerative diseases.

Physically active life style is associated with increased grey matter brain volume in a medial parieto-frontal network.

To examine the association between the amount of sports activity performed during leisure time and gray matter volume (GMV) of the brain we investigated differences in GMV in a large cohort study of community-dwelling older adults. 967 individuals indicated their average weekly sports activity via a questionnaire, and underwent high resolution T1-weighted structural imaging of the brain. We used voxel based morphometry (CAT 12) in a region of interest approach for (1) comparing participants with higher versus lower sports activity (median split) and (2) calculating a linear regression on GMV and sports activity. We carefully corrected for other factors known to have an impact on GMV (sex, age, total brain volume, education, cigarettes and alcohol consumption, body mass index) and excluded pathology (history of psychiatric or neurological disease; visual inspection of brain scans). Those participants who spend more time performing sports activity per week (median split with > 1 h/week) showed higher GMV in the dorsomedial frontal lobe, the superior parietal lobe, and the precuneus/cuneus area. When splitting participants by their median (55.5 years) into two groups we found a stronger protective effect of sports against age related GMV decline for the older part of the cohort. Overall, a more active lifestyle was associated with increased GMV in areas associated with self-awareness and working memory. These cohort data support data on the protective role of sports activity for the GMV.

Disturbed glutathione antioxidative defense is associated with structural brain changes in neuroleptic-naïve first-episode psychosis patients.

BACKGROUND: Oxidative stress and impaired antioxidant defense are reported in schizophrenia and are thought to be associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, negative symptomatology, and cognitive impairment. To test some of these assumptions we investigated the glutathione (GSH) antioxidant defense system (AODS) and brain structural abnormalities in drug-naïve individuals with first acute episode of psychosis (FEP). METHOD: The study involved 27 drug-naïve FEP patients and 31 healthy controls (HC). GSH AODS markers and TBARS (thiobarbituric acid reactive substances) were measured in blood plasma and erythrocytes. High-resolution T1-weighted 3T MRI were acquired from all subjects. To investigate brain structural abnormalities and effects of illness on interactions between GSH metabolites or enzyme activities and local grey matter density, voxel-based morphometry (VBM) with the computational anatomy toolbox (CAT12) was used. Symptomatology was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Symptom Checklist 1990 revised (SCL-90-R). RESULTS: (i) In FEP patients, glutathione reductase activity (GSR) was lower than in the HC group. GSR activity in plasma was inversely correlated with SCL-90-R scores of depression and PANSS scores of the negative symptom subscale. (ii) A reduction of GM was observed in left inferior frontal, bilateral temporal, as well as parietal cortices of FEP patients. (iii) Interaction analyses revealed an influence of illness on GSR/GM associations in the left orbitofrontal cortex (BA 47). CONCLUSION: Our findings support the notion of altered GSH antioxidative defense in untreated acute psychosis as a potential pathomechanism for localized brain structural abnormalities. This pathology relates to a key brain region of social cognition, affective motivation control and decision making, and is clinically accompanied by depressive and negative symptoms.

Volume versus surface-based cortical thickness measurements: A comparative study with healthy controls and multiple sclerosis patients.

The cerebral cortex is a highly folded outer layer of grey matter tissue that plays a key role in cognitive functions. In part, alterations of the cortex during development and disease can be captured by measuring the cortical thickness across the whole brain. Available software tools differ with regard to labor intensity and computational demands. In this study, we compared the computational anatomy toolbox (CAT), a recently proposed volume-based tool, with the well-established surface-based tool FreeSurfer. We observed that overall thickness measures were highly inter-correlated, although thickness estimates were systematically lower in CAT than in FreeSurfer. Comparison of multiple sclerosis (MS) patients with age-matched healthy control subjects showed highly comparable clusters of MS-related thinning for both methods. Likewise, both methods yielded comparable clusters of age-related cortical thinning, although correlations between age and average cortical thickness were stronger for FreeSurfer. Our data suggest that, for the analysis of cortical thickness, the volume-based CAT tool can be regarded a considerable alternative to the well-established surface-based FreeSurfer tool.

ZNF804A genetic variation (rs1344706) affects brain grey but not white matter in schizophrenia and healthy subjects.

BACKGROUND: Genetic variation in the gene encoding ZNF804A, a risk gene for schizophrenia, has been shown to affect brain functional endophenotypes of the disorder, while studies of white matter structure have been inconclusive. METHOD: We analysed effects of ZNF804A single nucleotide polymorphism rs1344706 on grey and white matter using voxel-based morphometry (VBM) in high-resolution T1-weighted magnetic resonance imaging scans of 62 schizophrenia patients and 54 matched healthy controls. RESULTS: We found a significant (p < 0.05, family-wise error corrected for multiple comparisons) interaction effect of diagnostic group x genotype for local grey matter in the left orbitofrontal and right and left lateral temporal cortices, where patients and controls showed diverging effects of genotype. Analysing the groups separately (at p < 0.001, uncorrected), variation in rs1344706 showed effects on brain structure within the schizophrenia patients in several areas including the left and right inferior temporal, right supramarginal/superior temporal, right and left inferior frontal, left frontopolar, right and left dorsolateral/ventrolateral prefrontal cortices, and the right thalamus, as well as effects within the healthy controls in left lateral temporal, right anterior insula and left orbitofrontal cortical areas. We did not find effects of genotype of regional white matter in either of the two cohorts. CONCLUSIONS: Our findings demonstrate effects of ZNF804A genetic variation on brain structure, with diverging regional effects in schizophrenia patients and healthy controls in frontal and temporal brain areas. These effects, however, might be dependent on the impact of other (genetic or non-genetic) disease factors.

Individualized Gaussian process-based prediction and detection of local and global gray matter abnormalities in elderly subjects.

Structural imaging based on MRI is an integral component of the clinical assessment of patients with potential dementia. We here propose an individualized Gaussian process-based inference scheme for clinical decision support in healthy and pathological aging elderly subjects using MRI. The approach aims at quantitative and transparent support for clinicians who aim to detect structural abnormalities in patients at risk of Alzheimer's disease or other types of dementia. Firstly, we introduce a generative model incorporating our knowledge about normative decline of local and global gray matter volume across the brain in elderly. By supposing smooth structural trajectories the models account for the general course of age-related structural decline as well as late-life accelerated loss. Considering healthy subjects' demography and global brain parameters as informative about normal brain aging variability affords individualized predictions in single cases. Using Gaussian process models as a normative reference, we predict new subjects' brain scans and quantify the local gray matter abnormalities in terms of Normative Probability Maps (NPM) and global z-scores. By integrating the observed expectation error and the predictive uncertainty, the local maps and global scores exploit the advantages of Bayesian inference for clinical decisions and provide a valuable extension of diagnostic information about pathological aging. We validate the approach in simulated data and real MRI data. We train the GP framework using 1238 healthy subjects with ages 18-94 years, and predict in 415 independent test subjects diagnosed as healthy controls, Mild Cognitive Impairment and Alzheimer's disease.

Partial least squares correlation of multivariate cognitive abilities and local brain structure in children and adolescents.

Intelligent behavior is not a one-dimensional phenomenon. Individual differences in human cognitive abilities might be therefore described by a 'cognitive manifold' of intercorrelated tests from partially independent domains of general intelligence and executive functions. However, the relationship between these individual differences and brain morphology is not yet fully understood. Here we take a multivariate approach to analyzing covariations across individuals in two feature spaces: the low-dimensional space of cognitive ability subtests and the high-dimensional space of local gray matter volume obtained from voxel-based morphometry. By exploiting a partial least squares correlation framework in a large sample of 286 healthy children and adolescents, we identify directions of maximum covariance between both spaces in terms of latent variable modeling. We obtain an orthogonal set of latent variables representing commonalities in the brain-behavior system, which emphasize specific neuronal networks involved in cognitive ability differences. We further explore the early lifespan maturation of the covariance between cognitive abilities and local gray matter volume. The dominant latent variable revealed positive weights across widespread gray matter regions (in the brain domain) and the strongest weights for parents' ratings of children's executive function (in the cognitive domain). The obtained latent variables for brain and cognitive abilities exhibited moderate correlations of 0.46-0.6. Moreover, the multivariate modeling revealed indications for a heterochronic formation of the association as a process of brain maturation across different age groups.

[Volume alterations in the gray matter of anosmic subjects. Lessons we can learn from voxel-based morphometry]. / Volumenänderungen der grauen Hirnsubstanz bei Anosmikern. Erkenntnisse durch voxelbasierte Morphometrie.

Alterations in the central nervous system in patients with a loss of sense of smell are well documented for the olfactory bulb (OB). Here we present a voxel-based morphometry (VBM) study on cerebral alterations in the gray matter of patients with anosmia above the OB. 3-Tesla MRI datasets were obtained from 17 patients with anosmia as well as from 17 normosmic controls. Data processing and evaluation was performed using the SPM5 software package (Wellcome Department of Imaging Neuroscience Group, London, UK) and the implemented VBM5 toolbox. Patients with anosmia showed a significant volume decrease in the gray matter in the primary olfactory cortex as well as in secondary olfactory areas (insular cortex, orbitofrontal cortex, cingulate cortex and hippocampus). Furthermore, volume decreases in areas like the nucleus accumbens with adjacent subcallosal gyrus and the dorsolateral prefrontal cortex were found. Longer disease duration was associated with more profound alterations in the gray matter. VBM is appropriate to document brain alterations in patients with olfactory disorders.

Gray matter alterations in parosmia.

Parosmia is a common olfactory disorder. In this condition, odors are perceived in a different quality than usual. This distorted olfactory percept is typically reported to be unpleasant. Little is known about the pathophysiology of this phenomenon. Previous studies demonstrated smaller volumes of the olfactory bulbs in patients with parosmia compared to subjects without parosmia. In order to investigate structural brain alterations in areas beyond the olfactory bulb, in the current study voxel-based morphometry was applied. A group of 22 parosmic patients was compared with control subjects matched for age- and sex, who exhibited a similar performance in olfactory tests. Performing a whole brain analysis, we found profound gray matter volume loss in the left anterior insula in parosmic patients. In an additional volume of interest analysis including primary and secondary olfactory areas, we also found volume loss in the right anterior insula, the anterior cingulate cortex, the hippocampus bilaterally, and the left medial orbitofrontal cortex. Many of these areas are critically involved in olfactory quality discrimination and odor memory. The present results indicate that reduced gray matter volume in brain regions supporting odor discrimination and memory is related to disturbed olfactory sensation in parosmia.

Voxel-based morphometry in individual patients: a pilot study in early Huntington disease.

BACKGROUND AND PURPOSE: Voxel-based morphometry (VBM) has proved a powerful method to detect subtle changes of gray matter (GM) at the group level but the role of VBM for the detection of GM changes in single subjects, especially in those with suspected neurodegenerative disorder, remains uncertain. Here, we performed single subject analyses in 22 patients in early stages of Huntington disease (HD), a neurodegenerative disorder with a well-known and characteristic pattern of GM loss. MATERIALS AND METHODS: We applied an ANCOVA with age and gender as covariates and corrected for multiple statistical tests by false discovery rate (P < 0.05). Each patient was compared to 133 healthy controls. The same procedure was applied to 22 of the controls matched for age and gender in a pair-wise manner. RESULTS: Our analyses yielded biologically plausible results in HD patients in which GM decrease within the caudate nucleus could be identified in 15 of the 16 most affected patients while GM decrease was found in only 1 control subject. Lowering the size of the control group yielded comparable results with 99 and 66 control subjects whereas sensitivity decreased with 33 control subjects. CONCLUSIONS: Our pilot study demonstrates a potential role of VBM for the detection of cerebral GM changes in single subjects with suspected neurodegenerative disorder.

Structural brain alterations in subjects at high-risk of psychosis: a voxel-based morphometric study.

Forty Untreated high-risk (HR) individuals for psychosis and 75 healthy control subjects (HC) matched for age, gender, handedness and educational level were investigated by structural MRI. HR subjects were recruited at the Early Detection and Intervention Centre for Mental Crises (FETZ) of the Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Germany. Measurements of gray matter volumes were performed by voxel-based morphometry using SPM5. The sample of HR subjects showed GM volume reductions in frontal, lateral temporal and medial temporal regions compared to the healthy control group. These regions are compatible with structural findings in the clinically apparent disease of schizophrenia.

Premotor Gray Matter Volume is Associated with Clinical Findings in Idiopathic and Genetically Determined Parkinson's Disease.

In the present voxel-based morphometric study, we investigated whether the severity and duration of disease are associated with alterations in gray matter volume (GMV) in symptomatic Parkin mutation carriers (sPARKIN-MC) and patients with idiopathic Parkinson's disease (iPD). Regression analyses revealed different negative correlations between GMV in cortical motor areas and the severity as well as the disease duration in sPARKIN-MC and iPD patients. SPARKIN-MC showed a less involvement of cortical motor areas, in particular in the supplementary motor area (SMA) than iPD patients. Specifically, in iPD patients, but not in sPARKIN-MC, there was a negative correlation between the SMA degeneration and the UPDRS-II item freezing. The different degeneration patterns may mirror diverse kinetics of the disease progress in these two groups of PD patients with different underlying etiologies.

Morphometric fingerprint of asymptomatic Parkin and PINK1 mutation carriers in the basal ganglia.

BACKGROUND: Mutations in the Parkin and PINK1 genes can cause parkinsonism. Since asymptomatic carriers of a single mutant allele of the Parkin or PINK1 gene display a presynaptic dopaminergic dysfunction in the striatum, they provide a unique in vivo model to study structural and functional reorganization in response to latent nigrostriatal dysfunction. We hypothesized that subclinical nigrostriatal neurodegeneration caused by these mutations would induce morphologic changes in the dysfunctional striatal gray matter. METHODS: In asymptomatic carriers of a heterozygous Parkin (n = 13) or PINK1 (n = 10) mutation and 23 age-and sex-matched individuals without a mutation, we applied observer independent region-of-interest and voxel-based morphometry to high-resolution structural MRIs. RESULTS: Relative to controls without a mutation, Parkin and PINK1 mutation carriers displayed a bilateral increase in gray matter volume in the putamen and the internal globus pallidus. In 8 of the 13 Parkin mutation carriers, the presynaptic dopaminergic function was studied with (18)F-DOPA PET. The metabolic-morphometric regression analysis revealed that the linear decrease in individual presynaptic striatal (18)F-DOPA uptake was linked to a reciprocal decrease in the striatal gray matter volume in the putamen bilaterally and in the left caudate nucleus. CONCLUSIONS: The alternative causes of the increased striatal gray matter volume may be either due to excessive levels of neuronal activity caused by chronic dopaminergic dysfunction or due to long-term adaptation to chronic nigrostriatal dysfunction actively compensating for the dopaminergic denervation. In any case, the results indicate that a genetically driven regional dysfunction may be imprinted in the structure of the dysfunctional brain region, for example in the striatum.

Voxel-based morphometry indicates relative preservation of the limbic prefrontal cortex in early Huntington disease.

In Huntington disease (HD), both the genetic defect and mutant gene product huntington are known but the exact mechanisms that lead to neuronal loss are poorly understood. Until now, the distribution of tissue loss throughout the brain has been investigated intensively. Here we searched for areas that, antipodal to the striatum, display grey-matter (GM) preservation. We performed high resolution T1-weighted magnetic resonance imaging and voxel-based morphometry in 46 patients in early HD and 46 healthy controls. We applied an analysis of covariance (ANCOVA) model with the total GM volume of each participant as covariate. In accordance with earlier reports, group comparisons revealed GM decrease in the striatum, insula, and thalamus as well as in dorsolateral frontal and occipital areas. In contrast, the limbic prefrontal cortex displayed GM preservation. Our findings support hypotheses that postulate differential involvement of frontosubcortical circuits in the pathophysiology of HD.

Voxel-based morphometry shows no decreases in cerebellar gray matter volume in essential tremor.

OBJECTIVE: To investigate cerebellar gray matter volume in patients with essential tremor (ET). METHODS: We used voxel-based morphometry (VBM) based on high-resolution T1-weighted MRI to compare gray and white matter density between 27 patients with ET and 27 age- and sex-matched healthy control subjects. Fourteen patients had only postural tremor, whereas 13 patients showed additional intention tremor. RESULTS: VBM failed to demonstrate regional decreases in gray and white matter volume in patients with ET. There was, however, an expansion in gray matter depending on the type of tremor. Compared with age-matched control groups, patients with intention tremor showed a relative expansion of gray matter bilaterally in the region of the temporoparietal junction and the right middle occipital cortex. CONCLUSIONS: The lack of a consistent decrease in gray and white matter density argues against a progressive neurodegenerative process in essential tremor that leads to a substantial decrease in cerebellar gray matter volume. Patients with predominant intention tremor show a relative expansion of gray matter areas involved in higher order visuospatial processing, which might represent a long-term result of adaptive reorganization compensating the higher demands on the visuospatial control of skilled movements in case of trembling.

Morphological basis for the spectrum of clinical deficits in spinocerebellar ataxia 17 (SCA17).

Spinocerebellar ataxia 17 (SCA17) is a rare genetic disorder characterized by cerebellar, extrapyramidal, pyramidal as well as psychiatric signs. The pathoanatomical basis of this disorder is still not well known. A total of 12 patients and 12 age- and sex-matched controls were examined by in vivo MRI voxel-based morphometry (VBM). Besides general patterns of disease-related brain atrophy, characteristic syndrome-related morphological changes in SCA17 patients were studied. In comparison with normal controls, SCA17 patients showed a pattern of degeneration of the grey matter centred around mesial cerebellar structures, occipito-parietal structures, the anterior putamen bilaterally, the thalamus and other parts of the motor network, reflecting the cerebellar, pyramidal and extrapyramidal signs. A correlation analysis revealed a clear association between the clinical cerebellar, extrapyramidal and psychiatric scores and degeneration in specific areas. Two degeneration patterns were found as follows: regarding motor dysfunction, atrophy of the grey matter involved mainly the cerebellum and other motor networks, in particular the basal ganglia. In contrast, correlations with psychiatric scores revealed grey matter degeneration patterns in the frontal and temporal lobe, the cuneus and cingulum. Most interestingly, there was a highly significant correlation between the clinical Mini-Mental State Examination scores and atrophy of the nucleus accumbens, probably accounting for the leading psychiatric signs.

Hippocampal volume in chronic posttraumatic stress disorder (PTSD): MRI study using two different evaluation methods.

UNLABELLED: The hippocampus is discussed as one of the key regions in the pathogenesis of Posttraumatic Stress Disorder (PTSD). MRI results concerning the volume of the hippocampus are, however, inconsistent. This may be due to the heterogeneity of patients' traumata or postprocessing of the imaging data. To overcome these problems, the present study investigates volume changes in well-characterized chronic PTSD patients in comparison to controls using two different evaluation methods. MATERIAL AND METHODS: 15 patients with chronic PTSD, traumatized at the same air show plane crash in 1988 (Ramstein, Germany), and 15 matched healthy controls participated in this study. All patients suffered from significant impairment by the PTSD; none had a history of drug or alcohol abuse. Hippocampus volume changes were processed by a semi-automated standard procedure performed with BRAINS2 as well as the voxel based morphometry (VBM) using SPM2. RESULTS: No differences in total brain grey or white matter were detected between patients and controls. No differences in total hippocampal volume or in right and left parts were seen, even when hippocampal volumes were corrected by total brain volume or correlated with clinical data. Finally, no significant differences were detected between patients and controls in hippocampal regions using VBM. DISCUSSION: This is the first study examining long-term changes in hippocampal volumes in chronic PTSD patients compared to matched controls using two different evaluation methods. Neither conventional volumetry nor VBM could detect any differences in the volume and structure. This supports the hypothesis that previously described hippocampal volume reduction is not necessarily due to PTSD or at least that, after 15 years, volume changes have been restored or have not yet developed.

Bilateral grey-matter increase in the putamen in primary blepharospasm.

BACKGROUND: Primary blepharospasm is a focal dystonia characterised by excessive involuntary closure of the eyelids. The pathophysiology of primary blepharospasm is unresolved. AIM: To pinpoint grey-matter changes that are associated with primary blepharospasm. METHODS: 16 right-handed patients with primary blepharospasm (mean age 67.4 (SD 4.3) years; 12 women) were compared with 16 healthy volunteers matched for sex and age. High-resolution T1-weighted magnetic resonance imaging of each participant was obtained and analysed by voxel-based morphometry, a method to detect regionally specific differences in grey matter between patients and control group. To evaluate whether the identified grey-matter changes were correlated with the duration of primary blepharospasm or botulinum neurotoxin treatment (BoNT), separate regression analyses were carried out. RESULTS: In patients with primary blepharospasm, grey-matter increase in the putamina was observed, whereas regression analyses did not indicate a correlation between grey-matter increases and the duration of primary blepharospasm or BoNT. Grey-matter decrease was detected in the left inferior parietal lobule; here regression analyses of grey-matter decrease showed a significant (p = 0.013) correlation of grey-matter decrease with the duration of BoNT. CONCLUSIONS: The data suggest structural changes in primary blepharospasm and point to a crucial role of the putamen for the pathophysiology of this focal dystonia.

A curvature-based approach to estimate local gyrification on the cortical surface.

Using magnetic resonance imaging and a new method to analyze local surface shape, we examined the effects of gender on gyrification in a large and well-matched sample of healthy subjects. Unlike traditional 2D methods that produce whole-brain measurements of cortical complexity or more sophisticated 3D parametric mesh-based techniques that allow only different sections (lobes) of the cortex to be investigated, we employed a novel approach with increased spatial resolution. Although our method is sensitive to similar cortical features like the classic whole-brain gyrification index (depths of sulci and heights of gyri), we are now able to provide detailed and regionally specific estimates of cortical convolution at thousands of points across the cortical surface without introducing any bias through the rater or the selected orientation of the slices. We revealed pronounced gender differences, showing increased gyrification in frontal and parietal regions in females compared to males that agree with recent regions-of-interest findings. In addition, we detected higher female gyrification in temporal and occipital cortices that was not previously identified in studies using more global measures. No cortical area was significantly more convoluted in males compared to females. Our results demonstrate the sensitivity of this automated approach for identifying very local changes in gyrification. This technique may serve to isolate regionally specific changes in fissuration/gyrification in neurodevelopmental or neuropsychiatric disorders.