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The profiles of cortical gyrification across schizophrenia, bipolar I disorder, and schizoaffective disorder have been studied to a limited extent, report discordant findings, and are rarely compared in the same study. Here we assess gyrification in a large dataset of psychotic disorder probands, categorized according to the DSM-IV. Furthermore, we explore gyrification changes with age across healthy controls and probands. Participants were recruited within the Bipolar-Schizophrenia Network of Intermediate Phenotypes study and received T1-MPRAGE and clinical assessment. Gyrification was measured using FreeSurfer 7.1.0. Pairwise t -tests were conducted in R, and age-related gyrification changes were analyzed in MATLAB. P values <0.05 after false discovery rate correction were considered significant. Significant hypogyria in schizophrenia, bipolar disorder, and schizoaffective disorder probands compared to controls was found, with a significant difference bilaterally in the frontal lobe between schizophrenia and bipolar disorder probands. Verbal memory was associated with gyrification in the right frontal and right cingulate cortex in schizophrenia. Age-fitted gyrification curves differed significantly among psychotic disorders and controls. Findings indicate hypogyria in DSM-IV psychotic disorders compared to controls and suggest differential patterns of gyrification across the different diagnoses. The study extends age related models of gyrification to psychotic disorder probands and supports that age-related differences in gyrification may differ across diagnoses. Fitted gyrification curves among probands categorized by DSM-IV significantly deviate from controls, with the model capturing early hypergyria and later hypogyria in schizophrenia compared to controls; this suggests unique disease and age-related changes in gyrification across psychotic disorders. [ABSTRACT FROM AUTHOR]

Previous studies have reported sex differences in cortical gyrification. Since most cortical folding is principally defined in utero, sex chromosomes as well as gonadal hormones are likely to influence sex‐specific aspects of local gyrification. Classic congenital adrenal hyperplasia (CAH) causes high levels of androgens during gestation in females, whereas levels in males are largely within the typical male range. Therefore, CAH provides an opportunity to study the possible effects of prenatal androgens on cortical gyrification. Here, we examined the vertex‐wise absolute mean curvature—a common estimate for cortical gyrification—in individuals with CAH (33 women and 20 men) and pair‐wise matched controls (33 women and 20 men). There was no significant main effect of CAH and no significant CAH‐by‐sex interaction. However, there was a significant main effect of sex in five cortical regions, where gyrification was increased in women compared to men. These regions were located on the lateral surface of the brain, specifically left middle frontal (rostral and caudal), right inferior frontal, left inferior parietal, and right occipital. There was no cortical region where gyrification was increased in men compared to women. Our findings do not only confirm prior reports of increased cortical gyrification in female brains but also suggest that cortical gyrification is not significantly affected by prenatal androgen exposure. Instead, cortical gyrification might be determined by sex chromosomes either directly or indirectly—the latter potentially by affecting the underlying architecture of the cortex or the size of the intracranial cavity, which is smaller in women. [ABSTRACT FROM AUTHOR]

Background: Obsessive–compulsive disorder (OCD) is thought to arise from dysconnectivity among interlinked brain regions resulting in a wide spectrum of clinical manifestations. Cortical gyrification, a key morphological feature of human cerebral cortex, has been considered associated with developmental connectivity in early life. Monitoring cortical gyrification alterations may provide new insights into the developmental pathogenesis of OCD. Methods: Sixty-two medication-naive patients with OCD and 59 healthy controls (HCs) were included in this study. Local gyrification index (LGI) was extracted from T1-weighted MRI data to identify the gyrification changes in OCD. Total distortion (splay, bend, or twist of fibers) was calculated using diffusion-weighted MRI data to examine the changes in white matter microstructure in patients with OCD. Results: Compared with HCs, patients with OCD showed significantly increased LGI in bilateral medial frontal gyrus and the right precuneus, where the mean LGI was positively correlated with anxiety score. Patients with OCD also showed significantly decreased total distortion in the body, genu, and splenium of the corpus callosum (CC), where the average distortion was negatively correlated with anxiety scores. Intriguingly, the mean LGI of the affected cortical regions was significantly correlated with the mean distortion of the affected white matter tracts in patients with OCD. Conclusions: We demonstrated associations among increased LGI, aberrant white matter geometry, and higher anxiety in patients with OCD. Our findings indicate that developmental dysconnectivity-driven alterations in cortical folding are one of the neural substrates underlying the clinical manifestations of OCD. [ABSTRACT FROM AUTHOR]

Introduction: The findings of epidemiological studies suggest that a relationship exists between the risk of schizophrenia and winter births in the Northern Hemisphere, which may affect the process of fetal neurodevelopment. However, it remains unclear whether birth seasons are associated with the brain morphological characteristics of patients within the schizophrenia spectrum. Methods: The present magnetic resonance imaging study using FreeSurfer software examined the effects of birth seasons (i.e., summer-born vs. winterborn) on the comprehensive brain surface characteristics of 101 patients with schizophrenia (48 summer- and 53 winter-born), 46 with schizotypal disorder (20 summer- and 26 winter-born), and 76 healthy control subjects (28 summerand 48 winter-born). Results: In comparisons with summer-born patients, winter-born patients, particularly those with schizophrenia, showed significantly increased gyrification mainly in the left lateral occipital and inferior temporal regions and right fronto-parietal region as well as cortical thinning in the right superior frontal region. Birth seasons did not significantly affect the local gyrification index or cortical thickness in healthy controls. Discussion: The present whole-brain surface-based analysis demonstrated that brain morphological characteristics reported in the schizophrenia spectrum were more pronounced in winter-born patients than in summer-born patients, suggesting the contribution of early neurodevelopmental factors associated with birth seasons to the pathophysiology of the schizophrenia spectrum. [ABSTRACT FROM AUTHOR]

Background: Impulse control disorders (ICD) in Parkinson's disease (PD) is highly multifactorial in etiology and has intricate neural mechanisms. Our multimodal neuroimaging study aimed to investigate the specific patterns of structure-function-neurotransmitter interactions underlying ICD. Methods: Thirty PD patients with ICD (PD-ICD), 30 without ICD (PD-NICD) and 32 healthy controls (HCs) were recruited. Gyrification and perivascular spaces (PVS) were computed to capture the alternations of cortical surface morphology and glymphatic function. Seed-based functional connectivity (FC) were performed to identify the corresponding functional changes. Further, JuSpace toolbox were employed for cross-modal correlations to evaluate whether the spatial patterns of functional alterations in ICD patients were associated with specific neurotransmitter system. Results: Compared to PD-NICD, PD-ICD patients showed hypogyrification and enlarged PVS volume fraction in the left orbitofrontal gyrus (OFG), as well as decreased FC between interhemispheric OFG. The interhemispheric OFG connectivity reduction was associated with spatial distribution of μ-opioid pathway (r = −0.186, p = 0.029, false discovery rate corrected). ICD severity was positively associated with the PVS volume fraction of left OFG (r = 0.422, p = 0.032). Furthermore, gyrification index (LGI) and percent PVS (pPVS) in OFG and their combined indicator showed good performance in differentiating PD-ICD from PD-NICD. Conclusions: Our findings indicated that the co-altered structure-function-neurotransmitter interactions of OFG might be involved in the pathogenesis of ICD.

TMEM161B encodes an evolutionarily conserved widely expressed novel 8-pass transmembrane protein of unknown function in human. Here we identify TMEM161B homozygous hypomorphic missense variants in our recessive polymicrogyria (PMG) cohort. Patients carrying TMEM161B mutations exhibit striking neocortical PMG and intellectual disability. Tmem161b knockout mice fail to develop midline hemispheric cleavage, whereas knock-in of patient mutations and patient-derived brain organoids show defects in apical cell polarity and radial glial scaffolding. We found that TMEM161B modulates actin filopodia, functioning upstream of the Rho-GTPase CDC42. Our data link TMEM161B with human PMG, likely regulating radial glia apical polarity during neocortical development.

Objective: This work investigates cortical thickness (CT) and gyrification patterns in Anorexia Nervosa (AN) before and after short‐term weight restoration using graph theory tools. Methods: 38 female adolescents with AN underwent structural magnetic resonance imaging scans at baseline and after ‐ on average ‐ 3.5 months following short‐term weight restoration while 53 age‐matched healthy controls (HCs) were scanned once. Graph measures were compared between groups and longitudinally within the AN group. Associations with clinical measures such as age of onset, duration of illness, BMI standard deviation score (BMI‐SDS), and longitudinal weight changes were tested via stepwise regression. Results: Cortical thickness graphs of patients with acute AN displayed lower modularity and small‐world index (SWI) than HCs. Modularity recovered after weight gain. Reduced global efficiency and SWI were observed in patients at baseline compared to HCs based on gyrification networks. Significant associations between local clustering of CT at admission and BMI‐SDS, and clustering/global efficiency of gyrification and duration of illness emerged. Conclusions: Our results indicate a shift towards less organised CT networks in patients with acute AN. After weight recovery, the disarrangement seems to be partially reduced. However, longer‐term follow‐ups are needed to determine whether cortical organizational patterns fully return to normal. Highlights: Patients with acute Anorexia Nervosa (AN) displayed a shift towards less organised cortical networks.After a short‐term weight restoration, alterations in cortical architecture seems to partially recover, suggesting the beneficial consequences of adequate nutritional programs on the brain structure.The associations between the organization of morphological patterns and clinical indices such as BMI standard deviation score (BMI‐SDS) and duration of the disorder support and emphasise the importance of an early and thorough weight rehabilitation in the treatment of AN. [ABSTRACT FROM AUTHOR]

Simple Summary: The mammalian cerebral cortex is believed to have gained complexity partly because of the abundance of specific cell types, collectively called basal progenitors. If these cells are deficient in the developing brain, it can lead to cortical structure anomalies, which have implications for defective brain function. Certain regulatory molecules have been found to control the production of basal progenitors during brain development. Key amongst them is the Paired Box 6 (Pax6) transcription factor and a chromatin modification mark called histone 3 lysine 9 acetylation (H3K9ac). However, our knowledge of how these regulatory factors interact to drive the generation of basal progenitors is insufficient. In this current work, we found that the enzyme involved in the acetylation of histone 3 at the 9th lysine interacts with Pax6 at the loci of genes critical for the production and amplification of the basal progenitor cell pool. As such, when both factors are decoupled or downregulated, it leads to depletion of the basal progenitor cells, resulting in a reduction in cortical development. The new mechanism identified deepens our understanding of cerebral cortex development and provides potential therapeutic cues for remedying brain abnormalities stemming from basal progenitor cell deficiency. Enrichment of basal progenitors (BPs) in the developing neocortex is a central driver of cortical enlargement. The transcription factor Pax6 is known as an essential regulator in generation of BPs. H3 lysine 9 acetylation (H3K9ac) has emerged as a crucial epigenetic mechanism that activates the gene expression program required for BP pool amplification. In this current work, we applied immunohistochemistry, RNA sequencing, chromatin immunoprecipitation and sequencing, and the yeast two-hybrid assay to reveal that the BP-genic effect of H3 acetylation is dependent on Pax6 functionality in the developing mouse cortex. In the presence of Pax6, increased H3 acetylation caused BP pool expansion, leading to enhanced neurogenesis, which evoked expansion and quasi-convolution of the mouse neocortex. Interestingly, H3 acetylation activation exacerbates the BP depletion and corticogenesis reduction effect of Pax6 ablation in cortex-specific Pax6 mutants. Furthermore, we found that H3K9 acetyltransferase KAT2A/GCN5 interacts with Pax6 and potentiates Pax6-dependent transcriptional activity. This explains a genome-wide lack of H3K9ac, especially in the promoter regions of BP-genic genes, in the Pax6 mutant cortex. Together, these findings reveal a mechanistic coupling of H3 acetylation and Pax6 in orchestrating BP production and cortical expansion through the promotion of a BP gene expression program during cortical development. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a severe mental disorder characterized by high heritability rates. Widespread brain cortical alterations have been reported in BD patients, mostly involving the frontal, temporal and parietal regions. Importantly, also unaffected relatives of BD patients (BD-RELs) present abnormalities in cortical measures, which are not influenced by disease-related factors, such as medication use and illness duration. Here, we collected all available evidence on cortical measures in BD-RELs to further our knowledge on the potential cortical alterations associated with the vulnerability and the resilience to BD. A search on PubMed, Web of Science and Scopus was performed to identify neuroimaging studies exploring cortical alterations in BD-RELs, including cortical thickness (CT), surface area (SA), gyrification (GI) and cortical complexity. Eleven studies were included. Of these, five assessed CT, five examined CT and SA and one explored CT, SA and GI. Overall, a heterogeneous pattern of cortical alterations emerged. The areas more consistently linked with genetic liability for BD were the prefrontal and sensorimotor regions. Mixed evidence was reported in the temporal and cingulate areas. The small sample size and the heterogeneity in terms of methodologies and the characteristics of the participants limit the generalizability of our results. Our findings suggest that the genetic liability for BD is related to reduced CT in the prefrontal cortex, which might be a marker of risk for BD, and increased CT within the sensorimotor cortex, which could represent a marker of resilience. • Brain alterations in BD-RELs could be linked to predisposition or resilience to BD. • This review summarizes cortical alterations in BD-RELs. • Reduced CT in the IFG and OFC might be a marker of risk for BD. • Increased CT in the sensorimotor cortex could represent a marker of resilience. • Results are heterogeneous and need to be replicated in future studies. [ABSTRACT FROM AUTHOR]

Type 2 diabetes has an effect on brain structure, including cortical gyrification. The significance of these changes is better understood if assessed over time. However, there is a lack of studies assessing longitudinally the effect of this disease with complex aethology in gyrification. While changes in this feature have been associated mainly with genetic legacy, our study allowed to shed light on the effect of the variation of glycaemic profile over time in gyrification in this metabolic disease. In this longitudinal study, we analysed brain anatomical magnetic resonance images of 15 participants with type 2 diabetes and 13 healthy control participants to investigate the impact of this metabolic disease on the gyrification index over a 7‐year period. We observed a significant interaction between time and group in six regions, four of which (left precentral gyrus, left gyrus rectus, left subcentral gyrus and sulci and right inferior temporal gyrus) showed an increase in gyrification in type 2 diabetes and a decrease in the control group and the two others (left pericallosal sulcus and right inferior frontal sulcus) the opposite pattern. The variation of the gyrification was correlated with the variation of the glycaemic profile. Following the interaction, the simple main effect of time in each group separately has shown that in the group with diabetes, there were more regions susceptible to alterations of gyrification. In sum, our results raise credit for the possibility that glycaemic control also might influence gyrification in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objectives: Prenatal surgery is offered for selected fetuses with open spina bifida (OSB) to improve long‐term outcome. We studied the effect of fetal OSB surgery on brain development using advanced magnetic resonance imaging (MRI) techniques to quantify the volume, surface area and shape of cerebral structures and to analyze surface curvature by means of parameters that correspond to gyrification. Methods: We compared MRI data from 29 fetuses with OSB before fetal surgery (mean gestational age (GA), 23 + 3 weeks) and at 1 and 6 weeks after surgery, with that of 36 GA‐matched control fetuses (GA range, 21 + 2 to 36 + 2 weeks). Automated super‐resolution reconstruction provided three‐dimensional isotropic volumetric brain images. Unmyelinated white matter, cerebellum and ventricles were segmented automatically and refined manually, after which volume, surface area and shape parameter (volume/surface area) were quantified. Mathematical markers (shape index (SI) and curvedness) were used to measure gyrification. Parameters were assessed according to lesion type (myelomeningocele vs myeloschisis (MS)), postoperative persistence of hindbrain herniation (HH) and the presence of supratentorial anomalies, namely partial agenesis of the corpus callosum (pACC) and heterotopia (HT). Results: Growth in ventricular volume per week and change in shape parameter per week were higher at 6 weeks after surgery in fetuses with OSB compared with controls (median, 2500.94 (interquartile range (IQR), 1689.70–3580.80) mm3/week vs 708.21 (IQR, 474.50–925.00) mm3/week; P < 0.001 and 0.075 (IQR, 0.047–0.112) mm/week vs 0.022 (IQR, 0.009–0.042) mm/week; P = 0.046, respectively). Ventricular volume growth increased 6 weeks after surgery in cases with pACC (P < 0.001) and those with persistent HH (P = 0.002). During that time period, the change in unmyelinated white‐matter shape parameter per week was decreased in OSB fetuses compared with controls (0.056 (IQR, 0.044–0.092) mm/week vs 0.159 (IQR, 0.100–0.247) mm/week; P = 0.002), particularly in cases with persistent HH (P = 0.011), MS (P = 0.015), HT (P = 0.022), HT with corpus callosum anomaly (P = 0.017) and persistent HH with corpus callosum anomaly (P = 0.007). At 6 weeks postoperatively, despite OSB fetuses having a lower rate of change in curvedness compared with controls (0.061 (IQR, 0.040–0.093) mm–1/week vs 0.094 (IQR, 0.070–0.146) mm–1/week; P < 0.001), reversing the trend seen at 1 week after surgery (0.144 (IQR, 0.099–0.236) mm–1/week vs 0.072 (IQR, 0.059–0.081) mm–1/week; P < 0.001), gyrification, as determined using SI, appeared to be increased in OSB fetuses overall compared with controls. This observation was more prominent in fetuses with pACC and those with severe ventriculomegaly (P‐value range, < 0.001 to 0.006). Conclusions: Following fetal OSB repair, volume, shape and curvedness of ventricles and unmyelinated white matter differed significantly compared with those of normal fetuses. Morphological brain changes after fetal surgery were not limited to effects on the circulation of cerebrospinal fluid. These observations may have implications for postnatal neurocognitive outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

BackgroundAn improved understanding of the neurodevelopmental differences between attention deficit hyperactivity disorder with and without prenatal alcohol exposure (ADHD + PAE and ADHD-PAE, respectively) is needed. Herein, we evaluated gyrification (cortical folding) in children with ADHD + PAE compared to that in children with familial ADHD-PAE and typically developing (TD) children.MethodsADHD + PAE (n = 37), ADHD-PAE (n = 25), and TD children (n = 27), aged 8-13 years, were compared on facial morphological, neurobehavioral, and neuroimaging assessments. Local gyrification index (LGI) maps were compared between groups using general linear modelling. Relationships between LGI and clincobehavioral parameters in children with ADHD ± PAE were evaluated using multivariate partial least squares.ResultsADHD + PAE and ADHD-PAE groups showed significantly lower LGI (relative to TD) in numerous regions, overlapping in medial prefrontal, parietal, and temporo-occipital cortices (p < 0.001). However, LGI in left mid-dorsolateral prefrontal cortex was uniquely lower in the ADHD + PAE group (p < 0.001). Partial least squares analysis identified one significant latent variable (accounting for 59.3 % of the crossblock correlation, p < 0.001), reflecting a significant relationship between a profile of lower LGI in prefrontal (including left mid-dorsolateral), insular, cingulate, temporal, and parietal cortices and a clinicobehavioral profile of PAE, including a flat philtrum and upper vermillion border, lower IQ, poorer behavioral regulation scores, and greater hyperactivity/impulsivity.ConclusionsChildren with ADHD + PAE uniquely demonstrate lower mid-dorsolateral LGI, with widespread lower LGI related to more severe facial dysmorphia and neurobehavioral impairments. These findings add insight into the brain bases of PAE symptoms, potentially informing more targeted ADHD treatments based on an objective differential diagnosis of ADHD + PAE vs. ADHD-PAE.

Background: Multivariate data-driven statistical approaches offer the opportunity to study multi-dimensional interdependences between a large set of biological parameters, such as high-dimensional brain imaging data. For gyrification, a putative marker of early neurodevelopment, direct comparisons of patterns among multiple psychiatric disorders and investigations of potential heterogeneity of gyrification within one disorder and a transdiagnostic characterization of neuroanatomical features are lacking. Methods: In this study we used a data-driven, multivariate statistical approach to analyze cortical gyrification in a large cohort of N = 1028 patients with major psychiatric disorders (Major depressive disorder: n = 783, bipolar disorder: n = 129, schizoaffective disorder: n = 44, schizophrenia: n = 72) to identify cluster patterns of gyrification beyond diagnostic categories. Results: Cluster analysis applied on gyrification data of 68 brain regions (DK-40 atlas) identified three clusters showing difference in overall (global) gyrification and minor regional variation (regions). Newly, data-driven subgroups are further discriminative in cognition and transdiagnostic disease risk factors. Conclusions: Results indicate that gyrification is associated with transdiagnostic risk factors rather than diagnostic categories and further imply a more global role of gyrification related to mental health than a disorder specific one. Our findings support previous studies highlighting the importance of association cortices involved in psychopathology. Explorative, data-driven approaches like ours can help to elucidate if the brain imaging data on hand and its a priori applied grouping actually has the potential to find meaningful effects or if previous hypotheses about the phenotype as well as its grouping have to be revisited.

Background: Identifying more homogenous subtypes of patients with obsessive–compulsive disorder (OCD) using biological evidence is critical for understanding complexities of the disorder in this heterogeneous population. Age of onset serves as a useful subtyping scheme for distinguishing OCD into two subgroups that aligns with neurodevelopmental perspectives. The underlying neurobiological markers for these distinct neurodevelopmental differences can be identified by investigating gyrification changes to establish biological evidence-based homogeneous subtypes. Methods: We compared whole-brain cortical gyrification in 84 patients with early-onset OCD, 84 patients with late-onset OCD, and 152 healthy controls (HCs) to identify potential markers for early neurodevelopmental deficits using the local gyrification index (lGI). Then, the relationships between lGI in clusters showing significant differences and performance in visuospatial memory and verbal fluency, which are considered trait-related neurocognitive impairments in OCD, were further examined in early-onset OCD patients. Results: The early-onset OCD patients exhibited significantly greater gyrification than those with late-onset OCD patients and HCs in frontoparietal and cingulate regions, including the bilateral precentral, postcentral, precuneus, paracentral, posterior cingulate, superior frontal, and caudal anterior cingulate gyri. Moreover, impaired neurocognitive functions in early-onset OCD patients were correlated with increased gyrification. Conclusions: Our findings provide a neurobiological marker to distinguish the OCD population into more neurodevelopmentally homogeneous subtypes, which may contribute to the understanding of the neurodevelopmental underpinnings of an etiology in early-onset OCD consistent with the accumulated phenotypic evidence of greater neurodevelopmental deficits in early-onset OCD than in late-onset OCD. [ABSTRACT FROM AUTHOR]

Secondary lissencephaly evolved in mice due to effects on neurogenesis and the tangential distribution of neurons. Signaling pathways that help maintain lissencephaly are still poorly understood. We show that inactivating Twist1 in the primitive meninges causes cortical folding in mice. Cell proliferation in the meninges is reduced, causing loss of arachnoid fibroblasts that express Raldh2, an enzyme required for retinoic acid synthesis. Regionalized loss of Raldh2 in the dorsolateral meninges is first detected when folding begins. The ventricular zone expands and the forebrain lengthens at this time due to expansion of apical radial glia. As the cortex expands, regionalized differences in the levels of neurogenesis are coupled with changes to the tangential distribution of neurons. Consequentially, cortical growth at and adjacent to the midline accelerates with respect to more dorsolateral regions, resulting in cortical buckling and folding. Maternal retinoic acid supplementation suppresses cortical folding by normalizing forebrain length, neurogenesis and the tangential distribution of neurons. These results suggest that Twist1 and balanced retinoic acid signaling from the meninges are required to maintain normal levels of neurogenesis and lissencephaly in mice. [ABSTRACT FROM AUTHOR]

Abstract Background Life-long early ART (started before age 2 years), often with periods of treatment interruption, is now the standard of care in pediatric HIV infection. Although cross-sectional studies have investigated HIV-related differences in cortical morphology in the setting of early ART and ART interruption, the long-term impact on cortical developmental trajectories is unclear. This study compares the longitudinal trajectories of cortical thickness and folding (gyrification) from age 5 to 9 years in a subset of children perinatally infected with HIV (CPHIV) from the Children with HIV Early antiRetroviral therapy (CHER) trial to age-matched children without HIV infection. Methods 75 CHER participants in follow-up care at FAMCRU (Family Centre for Research with Ubuntu), as well as 66 age-matched controls, received magnetic resonance imaging (MRI) on a 3 T Siemens Allegra at ages 5, 7 and/or 9 years. MR images were processed, and cortical surfaces reconstructed using the FreeSurfer longitudinal processing stream. Vertex-wise linear mixed effects (LME) analyses were performed across the whole brain to compare the means and linear rates of change of cortical thickness and gyrification from 5 to 9 years between CPHIV and controls, as well as to examine effects of ART interruption. Results Children without HIV demonstrated generalized cortical thinning from 5 to 9 years, with the rate of thinning varying by region, as well as regional age-related gyrification increases. Overall, the means and developmental trajectories of cortical thickness and gyrification were similar in CPHIV. However, at an uncorrected p

Introduction: Since the number of insular gyri is higher in schizophrenia patients, it has potential as a marker of early neurodevelopmental deviations. However, it currently remains unknown whether the features of the insular gross anatomy are similar between schizophrenia patients and individuals at risk of psychosis. Furthermore, the relationship between anatomical variations in the insular cortex and cognitive function has not yet been clarified. Methods: The gross anatomical features (i.e., the number of gyri and development pattern of each gyrus) of the insular cortex were examined using magnetic resonance imaging, and their relationships with clinical characteristics were investigated in 57 subjects with an at-risk mental state (ARMS) and 63 schizophrenia patients in comparison with 61 healthy controls. Results: The number of insular gyri bilaterally in the anterior subdivision was higher in the ARMS and schizophrenia groups than in the control group. The schizophrenia group was also characterized by a higher number of insular gyri in the left posterior subdivision. A well-developed right middle short insular gyrus was associated with symptom severity in first-episode schizophrenia patients, whereas chronic schizophrenia patients with a well-developed left accessory gyrus were characterized by less severe cognitive impairments in motor and executive functions. The features of the insular gross anatomy were not associated with clinical characteristics in the ARMS group. Discussion: The features of the insular gross anatomy that were shared in the ARMS and schizophrenia groups may reflect a vulnerability to psychosis that may be attributed to anomalies in the early stages of neurodevelopment. However, the contribution of the insular gross anatomy to the clinical characteristics of schizophrenia may differ according to illness stages. [ABSTRACT FROM AUTHOR]

Autism has been associated with differences in the developmental trajectories of multiple neuroanatomical features, including cortical thickness, surface area, cortical volume, measures of gyrification, and the gray-white matter tissue contrast. These neuroimaging features have been proposed as intermediate phenotypes on the gradient from genomic variation to behavioral symptoms. Hence, examining what these proxy markers represent, i.e., disentangling their associated molecular and genomic underpinnings, could provide crucial insights into the etiology and pathophysiology of autism. In line with this, an increasing number of studies are exploring the association between neuroanatomical, cellular/molecular, and (epi)genetic variation in autism, both indirectly and directly in vivo and across age. In this review, we aim to summarize the existing literature in autism (and neurotypicals) to chart a putative pathway from (i) imaging-derived neuroanatomical cortical phenotypes to (ii) underlying (neuropathological) biological processes, and (iii) associated genomic variation. [ABSTRACT FROM AUTHOR]

Background: Life-long early ART (started before age 2 years), often with periods of treatment interruption, is now the standard of care in pediatric HIV infection. Although cross-sectional studies have investigated HIV-related differences in cortical morphology in the setting of early ART and ART interruption, the long-term impact on cortical developmental trajectories is unclear. This study compares the longitudinal trajectories of cortical thickness and folding (gyrification) from age 5 to 9 years in a subset of children perinatally infected with HIV (CPHIV) from the Children with HIV Early antiRetroviral therapy (CHER) trial to age-matched children without HIV infection. Methods: 75 CHER participants in follow-up care at FAMCRU (Family Centre for Research with Ubuntu), as well as 66 age-matched controls, received magnetic resonance imaging (MRI) on a 3 T Siemens Allegra at ages 5, 7 and/or 9 years. MR images were processed, and cortical surfaces reconstructed using the FreeSurfer longitudinal processing stream. Vertex-wise linear mixed effects (LME) analyses were performed across the whole brain to compare the means and linear rates of change of cortical thickness and gyrification from 5 to 9 years between CPHIV and controls, as well as to examine effects of ART interruption. Results: Children without HIV demonstrated generalized cortical thinning from 5 to 9 years, with the rate of thinning varying by region, as well as regional age-related gyrification increases. Overall, the means and developmental trajectories of cortical thickness and gyrification were similar in CPHIV. However, at an uncorrected p < 0.005, 6 regions were identified where the cortex of CPHIV was thicker than in uninfected children, namely bilateral insula, left supramarginal, lateral orbitofrontal and superior temporal, and right medial superior frontal regions. Planned ART interruption did not affect development of cortical morphometry. Conclusions: Although our results suggest that normal development of cortical morphometry between the ages of 5 and 9 years is preserved in CPHIV who started ART early, these findings require further confirmation with longitudinal follow-up through the vulnerable adolescent period. [ABSTRACT FROM AUTHOR]

The human cerebrum consists of a precise and stereotyped arrangement of lobes, primary gyri, and connectivity that underlies human cognition [P. Rakic, Nat. Rev. Neurosci. 10, 724-735 (2009)]. The development of this arrangement is less clear. Current models explain individual primary gyrification but largely do not account for the global configuration of the cerebral lobes [T. Tallinen, J. Y. Chung, J. S. Biggins, L. Mahadevan, Proc. Natl. Acad. Sci. U.S.A. 111, 12667-12672 (2014) and D. C. Van Essen, Nature 385, 313-318 (1997)]. The insula, buried in the depths of the Sylvian fissure, is unique in terms of gyral anatomy and size. Here, we quantitatively show that the insula has unique morphology and location in the cerebrum and that these key differences emerge during fetal development. Finally, we identify quantitative differences in developmental migration patterns to the insula that may underlie these differences. We calculated morphologic data in the insula and other lobes in adults (N = 107) and in an in utero fetal brain atlas (N = 81 healthy fetuses). In utero, the insula grows an order of magnitude slower than the other lobes and demonstrates shallower sulci, less curvature, and less surface complexity both in adults and progressively throughout fetal development. Spherical projection analysis demonstrates that the lenticular nuclei obstruct 60 to 70% of radial pathways from the ventricular zone (VZ) to the insula, forcing a curved migration to the insula in contrast to a direct radial pathway. Using fetal diffusion tractography, we identify radial glial fascicles that originate from the VZ and curve around the lenticular nuclei to form the insula. These results confirm existing models of radial migration to the cortex and illustrate findings that suggest differential insular and cerebral development, laying the groundwork to understand cerebral malformations and insular function and pathologies. [ABSTRACT FROM AUTHOR]

Background and objectives: Cortical structural changes in major depressive disorder (MDD) are usually studied using a voxel-based morphometry approach to delineate the cortical gray matter volume. Among cortical structures, gyrification patterns are considered a relatively stable indicator. In this study, we investigated differences in gyrification patterns between MDD patients and healthy controls (HCs) and explored the association of gyrification patterns with plasma brain-derived neurotrophic factor (BDNF) levels and depressive symptoms in MDD patients. Methods:We evaluated 79 MDD patients and 94 HCs and assessed depression severity in the patients using the 17-item Hamilton Depression Rating Scale (HAM-D). Blood samples of both groups were collected to measure plasma BDNF levels. Magnetic resonance imaging (MRI) data were obtained using three-dimensional fast-spoiled gradient-recalled acquisition. Differences in plasma BDNF levels between groups were examined using the Mann-Whitney U test. Principal component analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) were conducted to investigate the gyrification patterns which were significantly different between the groups, i.e., those with variable importance in projection (VIP) scores of >1.5 and p-value < 0.05 in multiple regression analyses adjusted for age and sex. Finally, multiple regression analysis was performed on the selected gyrification patterns to examine their association with BDNF levels in the two groups and HAM-D in the patients. Results: There were no significant differences in plasma BDNF levels between the groups. We found that 108 (71.0%) of 152 total local gyrification indices were MDD < HC. We identified 10 disease-differentiating factors based on critical gyrification features (VIP > 1.5 and p-value adjusted for age and sex < 0.05). However, we found no significant correlations between the 10 gyrification patterns and plasma BDNF levels and no interaction with group. Moreover, no significant correlations were observed between the local gyrification indices and HAM-D total scores. Conclusion: These results suggest that abnormal early cortical neurodevelopment may mediate vulnerability to MDD, independent of plasma BDNF levels and depressive symptoms. [ABSTRACT FROM AUTHOR]

Morphogenesis of the nervous system involves a highly complex spatio-temporal pattern of physical forces (mainly tension and pressure) acting on cells and tissues that are pliable but have an intricately organized cytoskeletal infrastructure. This review begins by covering basic principles of biomechanics and the core cytoskeletal toolkit used to regulate the shapes of cells and tissues during embryogenesis and neural development. It illustrates how the principle of 'tensegrity' provides a useful conceptual framework for understanding how cells dynamically respond to forces that are generated internally or applied externally. The latter part of the review builds on this foundation in considering the development of mammalian cerebral cortex. The main focus is on cortical expansion and folding – processes that take place over an extended period of prenatal and postnatal development. Cortical expansion and folding are likely to involve many complementary mechanisms, some related to regulating cell proliferation and migration and others related to specific types and patterns of mechanical tension and pressure. Three distinct multi-mechanism models are evaluated in relation to a set of 18 key experimental observations and findings. The Composite Tension Plus (CT+) model is introduced as an updated version of a previous multi-component Differential Expansion Sandwich Plus (DES+) model (Van Essen, 2020); the new CT+ model includes 10 distinct mechanisms and has the greatest explanatory power among published models to date. Much needs to be done in order to validate specific mechanistic components and to assess their relative importance in different species, and important directions for future research are suggested. • Mechanical tension mediated by the cytoskeleton plays a key role in many aspects of morphogenesis. • Expansion and folding of cerebral cortex are key to achieving a large cortical surface area while keeping wiring compact. • The Composite Tension Plus (CT+) model invokes 10 distinct mechanisms to account for cortical expansion and folding. [ABSTRACT FROM AUTHOR]

Epidemiological studies have shown that gestational age and birth weight are linked to cognitive performance in adults. On a neurobiological level, this effect is hypothesized to be related to cortical gyrification, which is determined primarily during fetal development. The relationships between gestational age, gyrification and specific cognitive abilities in adults are still poorly understood. In 542 healthy participants, gyrification indices were calculated from structural magnetic resonance imaging T1 data at 3 T using CAT12. After applying a battery of neuropsychological tests, neuropsychological factors were extracted with a factor analysis. We conducted regressions to test associations between gyrification and gestational age as well as birth weight. Moderation analyses explored the relationships between gestational age, gyrification and neuropsychological factors. Gestational age is significantly positively associated with cortical folding in the left supramarginal, bilaterally in the superior frontal and the lingual cortex. We extracted two neuropsychological factors that describe language abilities and working memory/attention. The association between gyrification in the left superior frontal gyrus and working memory/attention was moderated by gestational age. Further, the association between gyrification in the left supramarginal cortex and both, working memory/attention as well as language, were moderated by gestational age. Gyrification is associated with gestational age and related to specific neuropsychological outcomes in healthy adulthood. Implications from these findings for the cortical neurodevelopment of cognitive domains and mental health are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Auditory verbal hallucinations (AVH) are transdiagnostic phenomena that can occur in several mental disorders, including borderline personality disorder (BPD). Despite the transdiagnostic relevance of these symptoms, very little is known about neural signatures of AVH in BPD. Methods: We used structural magnetic resonance imaging to investigate multiple markers of brain morphology in BPD patients presenting with a lifetime history of AVH (AVH, n = 6) versus BPD patients without AVH (nAVH, n = 10) and healthy controls (HC, n = 12). The Computational Anatomy Toolbox (CAT12) was used for surface-based morphometric analyses that considered cortical thickness (CTh), gyrification (CG), and complexity of cortical folding (CCF). Factorial models were used to explore differences between AVH patients and HC, as well as between the patient groups. Results: Compared to HC, AVH patients showed distinct abnormalities in key regions of the language network, i.e., aberrant CTh and CG in right superior temporal gyrus and abnormal CCF in left inferior frontal gyrus. Further abnormalities were found in right prefrontal cortex (CTh) and left orbitofrontal cortex (CCF). Compared to nAVH patients, individuals with AVH showed abnormal CTh in right prefrontal cortex, along with CCF differences in right transverse temporal, superior parietal, and parahippocampal gyri. CG differences between the patient groups were found in left orbitofrontal cortex. Conclusion: The data suggest a transdiagnostic neural signature of voice-hearing that converges on key regions involved in speech generation and perception, memory and executive control. It is possible that cortical features of distinct evolutionary and genetic origin, i.e., CTh and CG/CCF, differently contribute to AVH vulnerability in BPD. [ABSTRACT FROM AUTHOR]

The folding of the human brain mostly takes place in utero, making it challenging to study. After a few pioneer studies looking into it in post-mortem foetal specimen, modern approaches based on neuroimaging have allowed the community to investigate the folding process in vivo, its normal progression, its early disturbances, and its relationship to later functional outcomes. In this review article, we aimed to first give an overview of the current hypotheses on the mechanisms governing cortical folding. After describing the methodological difficulties raised by its study in fetuses, neonates and infants with magnetic resonance imaging (MRI), we reported our current understanding of sulcal pattern emergence in the developing brain. We then highlighted the functional relevance of early sulcal development, through recent insights about hemispheric asymmetries and early factors influencing this dynamic such as prematurity. Finally, we outlined how longitudinal studies have started to relate early folding markers and the child’s sensorimotor and cognitive outcome. Through this review, we hope to raise awareness on the potential of studying early sulcal patterns both from a fundamental and clinical perspective, as a window into early neurodevelopment and plasticity in relation to growth in utero and postnatal environment of the child.

Heschl's gyrus (HG), which includes primary auditory cortex, is highly variable in its shape (i.e. gyrification patterns), between hemispheres and across individuals. Differences in HG shape have been observed in the context of phonetic learning skill and expertise, and of professional musicianship, among others. Two of the most common configurations of HG include single HG, where a single transverse temporal gyrus is present, and common stem duplications (CSD), where a sulcus intermedius (SI) arises from the lateral aspect of HG. Here we describe a new toolbox, called ‘Multivariate Concavity Amplitude Index’ (MCAI), which automatically assesses the shape of HG. MCAI works on the output of TASH, our first toolbox which automatically segments HG, and computes continuous indices of concavity, which arise when sulci are present, along the outer perimeter of an inflated representation of HG, in a directional manner. Thus, MCAI provides a multivariate measure of shape, which is reproducible and sensitive to small variations in shape. We applied MCAI to structural magnetic resonance imaging (MRI) data of N=181 participants, including professional and amateur musicians and from non-musicians. Former studies have shown large variations in HG shape in the former groups. We validated MCAI by showing high correlations between the dominant (i.e. highest) lateral concavity values and continuous visual assessments of the degree of lateral gyrification of the first gyrus. As an application of MCAI, we also replicated previous visually obtained findings showing a higher likelihood of bilateral CSDs in musicians. MCAI opens a wide range of applications in evaluating HG shape in the context of individual differences, expertise, disorder and genetics.

Enrichment of basal progenitors (BPs) in the developing neocortex is a central driver of cortical enlargement. The transcription factor Pax6 is known as an essential regulator in generation of BPs. H3 lysine 9 acetylation (H3K9ac) has emerged as a crucial epigenetic mechanism that activates the gene expression program required for BP pool amplification. In this current work, we applied immunohistochemistry, RNA sequencing, chromatin immunoprecipitation and sequencing, and the yeast two-hybrid assay to reveal that the BP-genic effect of H3 acetylation is dependent on Pax6 functionality in the developing mouse cortex. In the presence of Pax6, increased H3 acetylation caused BP pool expansion, leading to enhanced neurogenesis, which evoked expansion and quasi-convolution of the mouse neocortex. Interestingly, H3 acetylation activation exacerbates the BP depletion and corticogenesis reduction effect of Pax6 ablation in cortex-specific Pax6 mutants. Furthermore, we found that H3K9 acetyltransferase KAT2A/GCN5 interacts with Pax6 and potentiates Pax6-dependent transcriptional activity. This explains a genome-wide lack of H3K9ac, especially in the promoter regions of BP-genic genes, in the Pax6 mutant cortex. Together, these findings reveal a mechanistic coupling of H3 acetylation and Pax6 in orchestrating BP production and cortical expansion through the promotion of a BP gene expression program during cortical development.

Local gyrification index (LGI), a metric quantifying cortical folding, was evaluated in 105 boys with autism spectrum disorder (ASD) and 49 typically developing (TD) boys at 3 and 5 years-of-age. At 3 years-of-age, boys with ASD had reduced gyrification in the fusiform gyrus compared with TD boys. A longitudinal evaluation from 3 to 5 years revealed that while TD boys had stable/decreasing LGI, boys with ASD had increasing LGI in right inferior temporal gyrus, right inferior frontal gyrus, right inferior parietal lobule, and stable LGI in left lingual gyrus. LGI was also examined in a previously defined neurophenotype of boys with ASD and disproportionate megalencephaly. At 3 years-of-age, this subgroup exhibited increased LGI in right dorsomedial prefrontal cortex, cingulate cortex, and paracentral cortex, and left cingulate cortex and superior frontal gyrus relative to TD boys and increased LGI in right paracentral lobule and parahippocampal gyrus, and left precentral gyrus compared with boys with ASD and normal brain size. In summary, this study identified alterations in the pattern and development of LGI during early childhood in ASD. Distinct patterns of alterations in subgroups of boys with ASD suggests that multiple neurophenotypes exist and boys with ASD and disproportionate megalencephaly should be evaluated separately.

The convolutions of the mammalian cerebral cortex allow the enlargement of its surface and addition of novel functional areas during evolution while minimizing expansion of the cranium. Cognitive neurodevelopmental disorders in humans, including microcephaly and lissencephaly, are often associated with impaired gyrification. In the classical model of gyrification, surface area is initially set by the number of radial units, and the forces driving cortical folding include neuronal growth, formation of neuropil, glial cell intercalation, and the patterned growth of subcortical white matter. An alternative model proposes that specified neurogenic hotspots in the outer subventricular zone (oSVZ) produce larger numbers of neurons that generate convexities in the cortex. This directly contradicts reports showing that cortical neurogenesis and settling of neurons into the cortical plate in primates, including humans, are completed well prior to the formation of secondary and tertiary gyri and indeed most primary gyri. In addition, during the main period of gyrification, the oSVZ produces mainly astrocytes and oligodendrocytes. Here we describe how rapid growth of intracortical neuropil, addition of glial cells, and enlargement of subcortical white matter in primates are the primary forces responsible for the post-neurogenic expansion of the cortical surface and formation of gyri during fetal development. Using immunohistochemistry for markers of proliferation and glial and neuronal progenitors combined with transcriptomic analysis, we show that neurogenesis in the ventricular zone and oSVZ is phased out and transitions to gliogenesis prior to gyral development. In summary, our data support the classical model of gyrification and provide insight into the pathogenesis of congenital cortical malformations. [ABSTRACT FROM AUTHOR]

Introduction: Interest in identifying the clinical implications of the neuropathophysiological background of schizophrenia is rising, including changes in cortical gyrification that may be due to neurodevelopmental abnormalities. Inpatients with schizophrenia can show abnormal gyrification of cortical regions correlated with the symptom severity. Methods: Our study included 36 patients that suffered an acute episode of schizophrenia and have undergone structural magnetic resonance imaging (MRI) to calculate the local gyrification index (LGI). Results: In the whole sample, the severity of symptoms significantly correlated with higher LGI in different cortical areas, including bilateral frontal, cingulate, parietal, temporal cortices, and right occipital cortex. Among these areas, patients with low hostility symptoms (LHS) compared to patients with high hostility symptoms (HHS) showed significantly lower LGI related to the severity of symptoms in bilateral frontal and temporal lobes. Discussion: The severity of psychopathology correlated with higher LGI in large portions of the cerebral cortex, possibly expressing abnormal neural development in schizophrenia. These findings could pave the way for further studies and future tailored diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Aim: Validating the vulnerabilities and pathologies underlying treatment‐resistant schizophrenia (TRS) is an important challenge in optimizing treatment. Gyrification and surface area (SA), reflecting neurodevelopmental features, have been linked to genetic vulnerability to schizophrenia. The aim of this study was to identify gyrification and SA abnormalities specific to TRS. Methods: We analyzed 3T magnetic resonance imaging findings of 24 healthy controls (HCs), 20 responders to first‐line antipsychotics (FL‐Resp), and 41 patients with TRS, including 19 clozapine responders (CLZ‐Resp) and 22 FL‐ and clozapine‐resistant patients (patients with ultratreatment‐resistant schizophrenia [URS]). The local gyrification index (LGI) and associated SA were analyzed across groups. Diagnostic accuracy was verified by receiver operating characteristic curve analysis. Results: Both CLZ‐Resp and URS had lower LGI values than HCs (P = 0.041, Hedges g [gH] = 0.75; P = 0.013, gH = 0.96) and FL‐Resp (P = 0.007, gH = 1.00; P = 0.002, gH = 1.31) in the left medial parietal cortex (Lt‐MPC). In addition, both CLZ‐Resp and URS had lower SA in the Lt‐MPC than FL‐Resp (P < 0.001, gH = 1.22; P < 0.001, gH = 1.75). LGI and SA were positively correlated in non‐TRS (FL‐Resp) (ρ = 0.64, P = 0.008) and TRS (CLZ‐Resp + URS) (ρ = 0.60, P < 0.001). The areas under the receiver operating characteristic curve for non‐TRS versus TRS with LGI and SA in the Lt‐MPC were 0.79 and 0.85, respectively. SA in the Lt‐MPC was inversely correlated with negative symptoms (ρ = −0.40, P = 0.018) and clozapine plasma levels (ρ = −0.35, P = 0.042) in TRS. Conclusion: LGI and SA in the Lt‐MPC, a functional hub in the default‐mode network, were abnormally reduced in TRS compared with non‐TRS. Thus, altered LGI and SA in the Lt‐MPC might be structural features associated with genetic vulnerability to TRS. [ABSTRACT FROM AUTHOR]

Introduction: comparative anatomy provides empirical facts for the classification of biological species on the basis of similarities or diversities of their anatomical characteristics. Animal models, especially rodents, are imperative tools for neuroscience research useful in elucidating brain pathologies. This study comparatively characterizes the anatomical features of the cerebrum of some rodent species; Wistar rat, Cavia porcellus, and Oryctolagus cuniculus using morphologic and microscopic assessments. Material and Methods: nine adult rodents (n= 3/species): Wistar rat, guinea pig (Cavia porcellus), and rabbit (Oryctolagus cuniculus) were used. Morphological and microscopic assessments including morphometrics of brain dimensions, gyrification, encephalization quotient (EQ), histology, and histometry of cerebral M1 region were conducted and features compared amongst species. Results: morphologically, brain dimensions revealed higher (p<0.05) values for rabbits among the rodent species. Gyrification was observed on the dorsal surface of cerebral hemispheres of the rodents, except in rats. Guinea pigs had the highest (p<0.05) EQ levels for species intelligence. Microscopically, layers III and V of cerebral M1 revealed similar population of cell types in all species. Histometric characteristics of pyramidal neurons in layer V were different (p<0.05) amongst the species with higher values in rabbits. No remarkable difference in cell distribution of cerebral M1 in layers III and V amongst the species. Conclusion: there exists morphologic variation in the brain features of compared rodent species and a small-scale variation in the cytoarchitectural features of the M1 cerebrum of the species. Results obtained are beneficial in identifying suitable species as potential models for certain neuroscience research. [ABSTRACT FROM AUTHOR]

Background Although neuroanatomical studies correlated to fibromyalgia (FM) are gaining increasing interest, the cortical morphology of patients are largely unknown, and data on cortical gyrification are scarce. The objective of the present study is to assess the cortical morphology in female patients with FM compared with healthy controls (HC) using surface-based morphometry (SBM) analysis of magnetic resonance imaging (MRI). Methods T1-MRIs and clinical data of 20 FM patients and 20 HC subjects were obtained from a public data set via OpenNeuro. For each subject, surface parameters including cortical thickness, local gyrification index (LGI), sulcal depth, and fractal dimensionality were estimated using SBM analysis. These data were compared between two groups controlled by age. The correlations between regional SBM parameters showing group differences and clinical profiles were analyzed. Results Compared with HC subjects, FM patients showed reduced cortical thickness in right primary motor cortex, lower LGI in right rostral anterior cingulate and higher sulcal depth in right precuneus (P  < 0.05 cluster level family- wise error corrected). In FM patients, correlation analysis showed that the cortical thickness in right primary motor cortex were inversely correlated with scores of pain catastrophizing scale (r = -0.498, P  = 0.030) and pain self-perception scale (r = -0.527, P  = 0.020), and disease duration (r = -0.488, P  = 0.034), respectively. Conclusions Our findings provide evidence of neuroanatomical aberrations in FM patients, which may provide insight into the neuropathology of FM. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a severe mental illness with a strong genetic component. Genetic variations have been involved in the risk of this disorder, including those mediating brain function and neurodevelopment. Early neurodevelopment and neuroprogression processes could be reflected in brain gyrification patterns and help optimize the prediction and diagnosis of such disorders that is often delayed. Previous neuroimaging studies using this measure in patients with bipolar disorder revealed controversial results. This systematic review aimed to summarize available neuroimaging investigations on gyrification in BD compared to healthy controls (HC) and/or other psychiatric groups. Fourteen studies including 733 patients with BD, 585 patients with schizophrenia (SCZ), 90 with schizoaffective disorder (SZA), and 1380 healthy subjects were identified. Overall, a heterogeneous pattern of gyrification emerged between patients with BD and HC. Interestingly, increased gyrification or no differences were also observed in patients with BD compared to those with the schizophrenia-spectrum disorders. Furthermore, relatives of patients with BD showed lower or no differences in gyrification compared to healthy subjects without a family history of affective illness. Differences in the design and in methodological approaches could have contributed to the heterogeneity of the findings. The current review supports an altered brain gyrification pattern that underlies the pathophysiology of BD spanning large anatomical and functional neural networks, associated with altered cognitive functioning, difficulties in processing and affective regulation, and clinical symptoms. Longitudinal studies are needed to test different bipolar phenotypes and pharmacological effects on gyrification. [ABSTRACT FROM AUTHOR]

Greater cortical gyrification (GY) is linked with enhanced cognitive abilities and is also negatively related to cortical thickness (CT). Individuals who are congenitally blind (CB) exhibits remarkable functional brain plasticity which enables them to perform certain non-visual and cognitive tasks with supranormal abilities. For instance, extensive training using touch and audition enables CB people to develop impressive skills and there is evidence linking these skills to cross-modal activations of primary visual areas. There is a cascade of anatomical, morphometric and functional-connectivity changes in non-visual structures, volumetric reductions in several components of the visual system, and CT is also increased in CB. No study to date has explored GY changes in this population, and no study has explored how variations in CT are related to GY changes in CB. T1-weighted 3D structural magnetic resonance imaging scans were acquired to examine the effects of congenital visual deprivation in cortical structures in a healthy sample of 11 CB individuals (6 male) and 16 age-matched sighted controls (SC) (10 male). In this report, we show for the first time an increase in GY in several brain areas of CB individuals compared to SC, and a negative relationship between GY and CT in the CB brain in several different cortical areas. We discuss the implications of our findings and the contributions of developmental factors and synaptogenesis to the relationship between CT and GY in CB individuals compared to SC. F. [ABSTRACT FROM AUTHOR]

Nearly 75% of older adults in the US report balance problems. Although it is known that aging results in widespread brain atrophy, less is known about how brain structure relates to balance in aging. We collected T 1 - and diffusion-weighted MRI scans and measured postural sway of 36 young (18–34 years) and 22 older (66–84 years) adults during eyes open, eyes closed, eyes open-foam, and eyes closed-foam conditions. We calculated summary measures indicating visual, proprioceptive, and vestibular contributions to balance. Across both age groups, thinner cortex in multisensory integration regions was associated with greater reliance on visual inputs for balance. Greater gyrification within sensorimotor and parietal cortices was associated with greater reliance on proprioceptive inputs. Poorer vestibular function was correlated with thinner vestibular cortex, greater gyrification within sensorimotor, parietal, and frontal cortices, and lower free water-corrected axial diffusivity across the corona radiata and corpus callosum. These results expand scientific understanding of how individual differences in brain structure relate to balance and have implications for developing brain stimulation interventions to improve balance. [ABSTRACT FROM AUTHOR]

Inter-individual variations in the sulco-gyral pattern of Heschl's gyrus (HG) might contribute to emotional processing. However, it remains largely unknown whether borderline personality disorder (BPD) patients exhibit an altered HG gyrification pattern, compared with healthy individuals, and whether such a brain morphological feature, if present, might contribute to their clinical characteristics. The present study used magnetic resonance imaging to investigate the distribution of HG gyrification patterns (single or duplicated) and their relationship to clinical characteristics in teenage BPD patients with minimal treatment exposure. No significant difference was noted for the prevalence of HG patterns between 20 BPD and 20 healthy participants. However, the BPD participants with left duplicated HG were characterized by higher prevalence of comorbid disruptive behavior disorders, with higher externalizing score compared with those with left single HG. Our preliminary results suggest that neurodevelopmental pathology associated with gyral formation might be implicated in the neurobiology of early BPD, especially for emotional and behavioral control. [ABSTRACT FROM AUTHOR]

Impulse control disorders (ICD) in Parkinson's disease (PD) is highly multifactorial in etiology and has intricate neural mechanisms. Our multimodal neuroimaging study aimed to investigate the specific patterns of structure-function-neurotransmitter interactions underlying ICD. Thirty PD patients with ICD (PD-ICD), 30 without ICD (PD-NICD) and 32 healthy controls (HCs) were recruited. Gyrification and perivascular spaces (PVS) were computed to capture the alternations of cortical surface morphology and glymphatic function. Seed-based functional connectivity (FC) were performed to identify the corresponding functional changes. Further, JuSpace toolbox were employed for cross-modal correlations to evaluate whether the spatial patterns of functional alterations in ICD patients were associated with specific neurotransmitter system. Compared to PD-NICD, PD-ICD patients showed hypogyrification and enlarged PVS volume fraction in the left orbitofrontal gyrus (OFG), as well as decreased FC between interhemispheric OFG. The interhemispheric OFG connectivity reduction was associated with spatial distribution of μ-opioid pathway (r = −0.186, p = 0.029, false discovery rate corrected). ICD severity was positively associated with the PVS volume fraction of left OFG (r = 0.422, p = 0.032). Furthermore, gyrification index (LGI) and percent PVS (pPVS) in OFG and their combined indicator showed good performance in differentiating PD-ICD from PD-NICD. Our findings indicated that the co-altered structure-function-neurotransmitter interactions of OFG might be involved in the pathogenesis of ICD. • Structure-function-neurotransmitter interaction • Enlarged PVS • OFG hypogyrification [ABSTRACT FROM AUTHOR]

IntroductionInterest in identifying the clinical implications of the neuropathophysiological background of schizophrenia is rising, including changes in cortical gyrification that may be due to neurodevelopmental abnormalities. Inpatients with schizophrenia can show abnormal gyrification of cortical regions correlated with the symptom severity.MethodsOur study included 36 patients that suffered an acute episode of schizophrenia and have undergone structural magnetic resonance imaging (MRI) to calculate the local gyrification index (LGI).ResultsIn the whole sample, the severity of symptoms significantly correlated with higher LGI in different cortical areas, including bilateral frontal, cingulate, parietal, temporal cortices, and right occipital cortex. Among these areas, patients with low hostility symptoms (LHS) compared to patients with high hostility symptoms (HHS) showed significantly lower LGI related to the severity of symptoms in bilateral frontal and temporal lobes.DiscussionThe severity of psychopathology correlated with higher LGI in large portions of the cerebral cortex, possibly expressing abnormal neural development in schizophrenia. These findings could pave the way for further studies and future tailored diagnostic and therapeutic strategies.

Greater cortical gyrification (GY) is linked with enhanced cognitive abilities and is also negatively related to cortical thickness (CT). Individuals who are congenitally blind (CB) exhibits remarkable functional brain plasticity which enables them to perform certain non-visual and cognitive tasks with supranormal abilities. For instance, extensive training using touch and audition enables CB people to develop impressive skills and there is evidence linking these skills to cross-modal activations of primary visual areas. There is a cascade of anatomical, morphometric and functional-connectivity changes in non-visual structures, volumetric reductions in several components of the visual system, and CT is also increased in CB. No study to date has explored GY changes in this population, and no study has explored how variations in CT are related to GY changes in CB. T1-weighted 3D structural magnetic resonance imaging scans were acquired to examine the effects of congenital visual deprivation in cortical structures in a healthy sample of 11 CB individuals (6 male) and 16 age-matched sighted controls (SC) (10 male). In this report, we show for the first time an increase in GY in several brain areas of CB individuals compared to SC, and a negative relationship between GY and CT in the CB brain in several different cortical areas. We discuss the implications of our findings and the contributions of developmental factors and synaptogenesis to the relationship between CT and GY in CB individuals compared to SC. F.

IntroductionPatients with schizophrenia have a higher number of insular gyri; however, it currently remains unclear whether the brain characteristics of patients with schizotypal personality disorder (SPD), a mild form of schizophrenia, are similar. It is also unknown whether insular gross anatomical features are associated with the illness stages and clinical subtypes of schizophrenia.Materials and methodsThis magnetic resonance imaging study examined gross anatomical variations in the insular cortex of 133 patients with schizophrenia, 47 with SPD, and 88 healthy controls. The relationships between the insular gross anatomy and schizophrenia subgroups (71 first-episode and 58 chronic groups, 38 deficit and 37 non-deficit subtype groups) were also investigated.ResultsThe number of insular gyri was higher in the schizophrenia and SPD patients than in the controls, where the patients were characterized by well-developed accessory, middle short, and posterior long insular gyri. The insular gross anatomy did not significantly differ between the first-episode and chronic schizophrenia subgroups; however, the relationship between the developed accessory gyrus and more severe positive symptoms was specific to the first-episode group. The prevalence of a right middle short gyrus was higher in the deficit schizophrenia group than in the non-deficit group.DiscussionThese findings suggest that schizophrenia and SPD patients may share an altered insular gross morphology as a vulnerability factor associated with early neurodevelopmental anomalies, which may also contribute to positive symptomatology in the early illness stages and clinical subtypes of schizophrenia.

Gyrification is a fundamental property of the human cortex that is increasingly studied by basic and clinical neuroscience. However, it remains unclear if and how the global architecture of cortical folding varies with 3 interwoven sources of anatomical variation: brain size, sex, and sex chromosome dosage (SCD). Here, for 375 individuals spanning 7 karyotype groups (XX, XY, XXX, XYY, XXY, XXYY, XXXXY), we use structural neuroimaging to measure a global sulcation index (SI, total sulcal/cortical hull area) and both determinants of sulcal area: total sulcal length and mean sulcal depth. We detail large and patterned effects of sex and SCD across all folding metrics, but show that these effects are in fact largely consistent with the normative scaling of cortical folding in health: larger human brains have disproportionately high SI due to a relative expansion of sulcal area versus hull area, which arises because disproportionate sulcal lengthening overcomes a lack of proportionate sulcal deepening. Accounting for these normative allometries reveals 1) brain size-independent sulcal lengthening in males versus females, and 2) insensitivity of overall folding architecture to SCD. Our methodology and findings provide a novel context for future studies of human cortical folding in health and disease.

Aims: This research aimed to explore alterations in the local gyrification index (GI) and resting-state functional connectivity (RSFC) in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI). Methods: In this study, 126 T2DM patients with MCI (T2DM-MCI), 154 T2DM patients with normal cognition (T2DM-NC), and 167 healthy controls (HC) were recruited. All subjects underwent a battery of neuropsychological tests. A multimodal approach combining surface-based morphometry (SBM) and seed-based RSFC was used to determine the structural and functional alterations in patients with T2DM-MCI. The relationships among the GI, RSFC, cognitive ability, and clinical variables were characterized. Results: Compared with the T2DM-NC group and HC group, T2DM-MCI patients showed significantly reduced GI in the bilateral insular cortex. Decreased RSFC was found between the left insula and right precuneus, and the right superior frontal gyrus (SFG). The altered GI was correlated with T2DM duration, global cognition, and episodic memory. The mediation effects of RSFC on the association between GI and cognition were not statistically significant. Conclusion: Our results suggest that GI may serve as a novel neuroimaging biomarker to predict T2DM-related MCI and help us to improve the understanding of the neuropathological effects of T2DM-related MCI. [ABSTRACT FROM AUTHOR]

Insight into illness in schizophrenia (SZ) patients has a major impact on treatment adherence and outcome. Previous studies have linked distinct deviations of brain structure to illness insight, specifically in frontoparietal and subcortical regions. Some of these abnormalities are thought to reflect aberrant cortical development. In this study, we used cross-sectional data to examine associations between illness insight and two cortical surface markers that are known to follow distinct neurodevelopmental trajectories, i.e. cortical gyrification (CG) and thickness (CT). CG and CT was investigated in SZ patients (n = 82) and healthy controls (HC, n = 48) using 3 T structural magnetic resonance imaging. Illness insight in SZ patients was measured using the OSSTI scale, an instrument that provides information on two distinct dimensions of illness insight, i.e. treatment adherence (OSSTI-A) and identification of disease-related symptoms (OSSTI-I). CT and CG were computed using the Computational Anatomy Toolbox (CAT12). Whole-brain and regions-of-interest (ROI)-based analyses were performed. SZ patients showed higher CG in anterior cingulate, superior frontal and temporal gyrus and reduced CG in insular and superior frontal cortex when compared to HC. SZ patients showed decreased CT in pre- and paracentral, occipital, cingulate, frontoparietal and temporal regions. Illness insight in SZ patients was significantly associated with both CG and CT in the left inferior parietal lobule (OSSTI-A) and the right precentral gyrus (CG/OSSTI-A, CT/OSSTI-I). The data support a multi-parametric neuronal model with both pre- and postnatal brain developmental factors having an impact on illness insight in patients with SZ. [ABSTRACT FROM AUTHOR]

Cortical differences have been reported in Anorexia Nervosa (AN) compared with healthy controls (HC); however, it is unclear if Autism Spectrum Disorder (ASD) characteristics are related to these cortical differences. The aim of this study was to examine if structural measures were correlated to ASD traits in AN. In total 184 female participants participated in the study; 57 acutely underweight AN participants (AAN), 59 weight‐restored participants (WR) and 68 HC. Participants underwent structural magnetic resonance imaging as well as completing the Autism Diagnostic Observation schedule, second edition to examine ASD characteristics. Group differences in curvature, gyrification, surface area, thickness, global grey matter and white matter were measured. Correlation and regression analysis were conducted to examine the relationship between cortical measures and ASD characteristics. Two decreased gyrification clusters in the right post central and supramarginal gyrus and decreased global grey matter were observed in the AAN group compared to HC and WR. No correlations between ASD traits and structural measures existed. Our results suggest structural differences seen in individuals with AN do not appear to be related to ASD characteristics. Highlights: Though widespread structural differences have been reported in anorexia nervosa the relationship to autistic traits is under‐researched and unclear.In this study autistic characteristics were not correlated to structural measures or structural differences in anorexia nervosa.Possible reasons for our results including variation in underlying biological process between anorexia nervosa and autism, as well as heterogeneity within anorexia nervosa are discussed, along with strategies for future work. [ABSTRACT FROM AUTHOR]

Most schizophrenia patients experience psychotic relapses, which may compromise long-term outcome. However, it is difficult to objectively assess the actual risk of relapse for each patient as the biological changes underlying relapse remain unknown. The present study used magnetic resonance imaging (MRI) to investigate the relationship between brain gyrification pattern and subsequent relapse in patients with first-episode schizophrenia. The subjects consisted of 19 patients with and 33 patients without relapse during a 3-year clinical follow-up after baseline MRI scanning. Using FreeSurfer software, we compared the local gyrification index (LGI) between the relapsed and non-relapsed groups. In the relapsed group, we also explored the relationship among LGI and the number of relapses and time to first relapse after MRI scanning. Relapsed patients exhibited a significantly higher LGI in the bilateral parietal and left occipital areas than non-relapsed patients. In addition, the time to first relapse was negatively correlated with LGI in the right inferior temporal cortex. These findings suggest that increased LGI in the temporo-parieto-occipital regions in first-episode schizophrenia patients may be a potential prognostic biomarker that reflects relapse susceptibility in the early course of the illness. [ABSTRACT FROM AUTHOR]