Reduced gyrification in fetal growth restriction with prenatal magnetic resonance images.

Placental-related fetal growth restriction, resulting from placental dysfunction, impacts 3-5% of pregnancies and is linked to elevated risk of adverse neurodevelopmental outcomes. In response, the fetus employs a mechanism known as brain-sparing, redirecting blood flow to the cerebral circuit, for adequate supply to the brain. In this study we aimed to quantitatively evaluate disparities in gyrification and brain volumes among fetal growth restriction, small for gestational age and appropriate-for gestational-age fetuses. Additionally, we compared fetal growth restriction fetuses with and without brain-sparing. The study encompassed 106 fetuses: 35 fetal growth restriction (14 with and 21 without brain-sparing), 8 small for gestational age, and 63 appropriate for gestational age. Gyrification, supratentorial, and infratentorial brain volumes were automatically computed from T2-weighted magnetic resonance images, following semi-automatic brain segmentation. Fetal growth restriction fetuses exhibited significantly reduced gyrification and brain volumes compared to appropriate for gestational age (P < 0.001). Small for gestational age fetuses displayed significantly reduced gyrification (P = 0.038) and smaller supratentorial volume (P < 0.001) compared to appropriate for gestational age. Moreover, fetal growth restriction fetuses with BS demonstrated reduced gyrification compared to those without BS (P = 0.04), with no significant differences observed in brain volumes. These findings demonstrate that brain development is affected in fetuses with fetal growth restriction, more severely than in small for gestational age, and support the concept that vasodilatation of the fetal middle cerebral artery reflects more severe hypoxemia, affecting brain development.

Toward a better understanding of how a gyrified brain develops.

The size and shape of the cerebral cortex have changed dramatically across evolution. For some species, the cortex remains smooth (lissencephalic) throughout their lifetime, while for other species, including humans and other primates, the cortex increases substantially in size and becomes folded (gyrencephalic). A folded cortex boasts substantially increased surface area, cortical thickness, and neuronal density, and it is therefore associated with higher-order cognitive abilities. The mechanisms that drive gyrification in some species, while others remain lissencephalic despite many shared neurodevelopmental features, have been a topic of investigation for many decades, giving rise to multiple perspectives of how the gyrified cerebral cortex acquires its unique shape. Recently, a structurally unique germinal layer, known as the outer subventricular zone, and the specialized cell type that populates it, called basal radial glial cells, were identified, and these have been shown to be indispensable for cortical expansion and folding. Transcriptional analyses and gene manipulation models have provided an invaluable insight into many of the key cellular and genetic drivers of gyrification. However, the degree to which certain biomechanical, genetic, and cellular processes drive gyrification remains under investigation. This review considers the key aspects of cerebral expansion and folding that have been identified to date and how theories of gyrification have evolved to incorporate this new knowledge.

Multimodal neuroimaging fusion unravel structural-functional-neurotransmitter change in Parkinson's disease with impulse control disorders.

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.

Cortical gyrification in women and men and the (missing) link to prenatal androgens.

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.

Gyrification across psychotic disorders: A bipolar-schizophrenia network of intermediate phenotypes study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Increased brain gyrification and cortical thinning in winter-born patients with schizophrenia spectrum.

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. winter-born) 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 summer- and 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.

Multimodal neural correlates of dispositional resilience among healthy individuals.

Resilient individuals are less likely to develop psychiatric disorders despite extreme psychological distress. This study investigated the multimodal structural neural correlates of dispositional resilience among healthy individuals. Participants included 92 healthy individuals. The Korean version of the Connor-Davidson Resilience Scale and other psychological measures were used. Gray matter volumes (GMVs), cortical thickness, local gyrification index (LGI), and white matter (WM) microstructures were analyzed using voxel-based morphometry, FreeSurfer, and tract-based spatial statistics, respectively. Higher resilient individuals showed significantly higher GMVs in the inferior frontal gyrus (IFG), increased LGI in the insula, and lower fractional anisotropy values in the superior longitudinal fasciculus II (SLF II). These resilience's neural correlates were associated with good quality of life in physical functioning or general health and low levels of depression. Therefore, the GMVs in the IFG, LGI in the insula, and WM microstructures in the SLF II can be associated with resilience that contributes to emotional regulation, empathy, and social cognition.

Corrigendum: Cortical gyrification pattern of depression in Parkinson's disease: a neuroimaging marker for disease severity?

[This corrects the article DOI: 10.3389/fnagi.2023.1241516.].

H3 Acetylation-Induced Basal Progenitor Generation and Neocortex Expansion Depends on the Transcription Factor Pax6.

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.

Assessing cortical features in early stage ASD children.

Autism Spectrum Disorder (ASD) is defined as a neurodevelopmental disorder largely investigated in the neurologic field. Recently, neuroimaging studies have been conducted in order to investigate cerebral morphologic alterations in ASD patients, demonstrating an atypical brain development before the clinical manifestations of the disorder. Cortical Thickness (CT) and Local Gyrification Index (LGI) distribution for ASD children were investigated in this study, with the aim to evaluate possible relationship between brain measures and individual characteristics (i.e., IQ and verbal ability). 3D T1-w sequences from 129 ASD and 58 age-matched Healthy Controls (HC) were acquired and processed in order to assess CT and LGI for each subject. Intergroup differences between ASD and HC were investigated, including analyses of 2 ASD subgroups, split according to patient verbal ability and IQ. When compared to HC, ASD showed increased CT and LGI within several brain areas, both as an overall group and as verbal ability an IQ subgroups. Moreover, when comparing language characteristics of the ASD subjects, those patients with verbal ability exhibit significant CT and LGI increase was found within the occipital lobe of right hemisphere. No significant results occurred when comparing ASD patients according to their IQ value. These results support the hypothesis of abnormal brain maturation in ASD since early childhood with differences among clinical subgroups suggesting different anatomical substrates underlying an aberrant connectivity.

Altered cortical and subcortical morphometric features and asymmetries in the subjective cognitive decline and mild cognitive impairment.

Introduction: This study aimed to evaluate morphological changes in cortical and subcortical regions and their asymmetrical differences in individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). These morphological changes may provide valuable insights into the early diagnosis and treatment of Alzheimer's disease (AD). Methods: We conducted structural MRI scans on a cohort comprising 62 SCD patients, 97 MCI patients, and 70 age-, sex-, and years of education-matched healthy controls (HC). Using Freesurfer, we quantified surface area, thickness, the local gyrification index (LGI) of cortical regions, and the volume of subcortical nuclei. Asymmetry measures were also calculated. Additionally, we explored the correlation between morphological changes and clinical variables related to cognitive decline. Results: Compared to HC, patients with MCI exhibited predominantly left-sided surface morphological changes in various brain regions, including the transverse temporal gyrus, superior temporal gyrus, insula, and pars opercularis. SCD patients showed relatively minor surface morphological changes, primarily in the insula and pars triangularis. Furthermore, MCI patients demonstrated reduced volumes in the anterior-superior region of the right hypothalamus, the fimbria of the bilateral hippocampus, and the anterior region of the left thalamus. These observed morphological changes were significantly associated with clinical ratings of cognitive decline. Conclusion: The findings of this study suggest that cortical and subcortical morphometric changes may contribute to cognitive impairment in MCI, while compensatory mechanisms may be at play in SCD to preserve cognitive function. These insights have the potential to aid in the early diagnosis and treatment of AD.

Hedgehog Signaling in Cortical Development.

The Hedgehog (Hh) pathway plays a crucial role in embryonic development, acting both as a morphogenic signal that organizes tissue formation and a potent mitogenic signal driving cell proliferation. Dysregulated Hh signaling leads to various developmental defects in the brain. This article aims to review the roles of Hh signaling in the development of the neocortex in the mammalian brain, focusing on its regulation of neural progenitor proliferation and neuronal production. The review will summarize studies on genetic mouse models that have targeted different components of the Hh pathway, such as the ligand Shh, the receptor Ptch1, the GPCR-like transducer Smo, the intracellular transducer Sufu, and the three Gli transcription factors. As key insights into the Hh signaling transduction mechanism were obtained from mouse models displaying neural tube defects, this review will also cover some studies on Hh signaling in neural tube development. The results from these genetic mouse models suggest an intriguing hypothesis that elevated Hh signaling may play a role in the gyrification of the brain in certain species. Additionally, the distinctive production of GABAergic interneurons in the dorsal cortex in the human brain may also be linked to the extension of Hh signaling from the ventral to the dorsal brain region. Overall, these results suggest key roles of Hh signaling as both a morphogenic and mitogenic signal during the forebrain development and imply the potential involvement of Hh signaling in the evolutionary expansion of the neocortex.

Left Cerebral Cortex Complexity in Patients with Major Depression Disorder: A Small-Sample Pilot Study.

Objective: To investigate cerebral cortical complexity (CCC) in patients with first-episode, drug-naive major depressive disorder (MDD) with source-based morphometry (SBM) analyses. Methods: We used the SBM parameters gyrification index (GI) and fractal dimension (FD) to evaluate CCC in 14 first-episode, drug-naive patients diagnosed with MDD. The severity of depression symptoms was assessed with the 17-item Hamilton Depression Scale (HAMD-17). GI and FD alterations in the MDD group, relative to healthy controls (HCs), were correlated with depression symptom severity with GI/FD. Results: Increased GIs in the MDD group, relative to HCs, were found mainly in the left postcentral gyrus, whereas GI reductions were found in the left angular gyrus, left lingual gyrus, left superior temporal gyrus, and left insular cortex. Increased FDs in the MDD group, relative to HCs, were located in the superior frontal gyrus. In contrast, decreased FDs were located in the left superior temporal gyrus and left superior frontal gyrus. Conclusion: Although the group differences in GI and FD values obtained did not withstand family-wise error (FWE) correction, the results show a consistent trend of alterations in left-hemisphere CCC in first-episode, drug-naive patients diagnosed with MDD. These findings support the hypothesis that there is a pattern of subtle neocortical aberrations in early-stage MDD.

Application of local gyrification index in the early diagnosis of Alzheimer disease / 中华放射学杂志

Objective To evaluate the role of local gyrification index (LGI) in the early diagnosis of Alzheimer disease(AD). Methods Thirty‐five amnestic‐type mild cognitive impairment patients (aMCI group), 34 mild AD patients (mild AD group) and 33 healthy volunteers (normal control group) were studied. All patients underwent high resolution MRI examination and mini‐mental state examination (MMSE). Using surface‐based morphometry, the FreeSurfer was employed to access LGI of vertex over every participant′s whole cortical surface, then we calculated the mean LGI (mLGI) of each subject′s left and right hemisphere separately. Taking age, gender and educational year as covariance, analysis of covariance was used to compare the difference of mLGI of left and right brain among 3 groups, then Bonferroni was done between every two groups. Analysis of covariance was applied to compare the difference of LGI of every participant among 3 groups, and Monte Carlo method was employed to perform multiple comparison corrections. The correlations between the MMSE scores and LGIs of the three groups were analyzed. Results Compared with normal control group(left 3.03±0.12,right 3.02±0.13), the mLGI of hemispheres in mild AD group(left 2.94±0.11,right 2.93±0.10) decreased respectively(P<0.05). The difference of mLGI of hemispheres between aMCI group(left 2.96 ± 0.10, right 2.96 ± 0.09) and normal control group had no statistical significance(P>0.05). The difference of mLGI of hemispheres between aMCI group and mild AD group also had no statistical significance(P>0.05). The aMCI group showed decrease of LGI in some brain regions located at the right temporal lobe, bilateral frontal and parietal lobe compared with the normal control group. While compared with aMCI group, decreased LGIs was presented in some brain regions located at bilateral temporal, occipital, frontal lobe and the right parietal lobe of mild AD group. There was a positive correlation between MMSE scores and LGIs of some brain regions in the bilateral temporal, occipital lobe, the left frontal lobe and the right parietal lobe in the three groups. Conclusion LGI is conductive in the early diagnosis of AD and can serve as an imaging marker for monitoring disease progresses.

A magnetic resonance imaging study on brain surface morphology change in patients with first-episode obsessive compulsive disorder / 中华行为医学与脑科学杂志

Objective To analyze the brain structure changes of the first-episode obsessive compulsive disorder (OCD) patients who were scanned by three-dimensional structure magnetic resonance imaging.Methods According to the diagnostic criteria of OCD in American Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-Ⅳ),the fist-episode obsessive compulsive disorder patients as case group(OCD,n=26) and the adult healthy volunteers as control group (control group,n=25) were selected.All subjects were assessed with Yale-Brown obsessive-compulsive scale(Y-BOCS),Hamilton Anxiety rating Scale (HAMA) and Hamilton Depression Rating Scale(HAMD),and then,they received 3D-MRI scanning runs.All the data was processed with freesurfer software and analyzed about cerebral cortical volume,cortical thickness,cortical surface area,the local gyrification index and subcortical nuclei volume.Results Compared with control group,the cerebral cortical thickness of OCD group increased at the left postcentral gyrus ((2.223±0.118)mm),left supramarginal gyrus ((2.486 ± 0.027) mm) and left parahippocampal gyrus ((2.399±0.164)mm).The cerebral cortical surface area larged at the right inferior frontal gyrus((1.036±0.079) mm2),right paracentral lobule ((0.827 ± 0.048) mm2) and medial orbitofrontal ((0.990 ± 0.083)mm2),and decreased at right superior parietal lobule ((0.779 ± 0.040) mm2),right inferior parietal lobule ((0.767±0.093) mm2) and right inferior temporal gyrus ((0.888±0.070) mm2).The cerebral cortical volume increased at the right inferior frontal gyrus((2.330±0.223) mm3).The cerebral cortical local gyrification index decreased at right middle temporal gyrus(2.893±0.288)and left inferior temporal gyrus(2.589±0.100).Conclusion The first-episode OCD patients have multiple changes of brain structures,and this changes were priority for the frontal lobes,orbital frontal,parietal lobe,temporal lobe and hippocampus.The changes in these regions maybe have close relationship with symptoms of OCD.

Alterations of Cortical Folding Patterns in Patients with Bipolar I Disorder: Analysis of Local Gyrification Index

OBJECTIVES: Local gyrification reflects the early neural development of cortical connectivity, and is regarded as a potential neural endophenotype in psychiatric disorders. Several studies have suggested altered local gyrification in patients with bipolar I disorder (BD-I). The purpose of the present study was to investigate the alterations in the cortical gyrification of whole brain cortices in patients with BD-I. METHODS: Twenty-two patients with BD-I and age and sex-matched 22 healthy controls (HC) were included in this study. All participants underwent T1-weighted structural magnetic resonance imaging (MRI). The local gyrification index (LGI) of 66 cortical regions were analyzed using the FreeSurfer (Athinoula A. Martinos Center for Biomedical Imaging). One-way analysis of covariance (ANCOVA) was used to analyze the difference of LGI values between two groups adjusting for age and sex as covariates. RESULTS: The patients with BD-I showed significant hypogyria in the left pars opercularis (uncorrected-p = 0.049), the left rostral anterior cingulate gyrus (uncorrected-p = 0.012), the left caudal anterior cingulate gyrus (uncorrected-p = 0.033). However, these findings were not significant after applying the multiple comparison correction. Severity or duration of illness were not significantly correlated with LGI in the patients with BD-I. CONCLUSIONS: Our results of lower LGI in the anterior cingulate cortex and the ventrolateral prefrontal cortex in the BD-I group implicate that altered cortical gyrification in neural circuits involved in emotion-processing may contribute to pathophysiology of BD-I.