Irritability Is Associated With Decreased Cortical Surface Area and Anxiety With Decreased Gyrification During Brain Development

Background: Brain development is of utmost importance for the emergence of psychiatric disorders, as the most severe of them arise before 25 years old. However, little is known regarding how early transdiagnostic symptoms, in a dimensional framework, are associated with cortical development. Anxiety and irritability are central vulnerability traits for subsequent mood and anxiety disorders. In this study, we investigate how these dimensions are related to structural changes in the brain to understand how they may increase the transition risk to full-blown disorders.Methods: We used the opportunity of an open access developmental cohort, the Healthy Brain Network, to investigate associations between cortical surface markers and irritability and anxiety scores as measured by parents and self-reports.Results: We found that in 658 young people (with a mean age of 11.6) the parental report of irritability is associated with decreased surface area in the bilateral rostral prefrontal cortex and the precuneus. Furthermore, parental reports of anxiety were associated with decreased local gyrification index in the anterior cingulate cortex and dorsomedial prefrontal cortex.Conclusions: These results are consistent with current models of emotion regulation network maturation, showing decreased surface area or gyrification index in regions associated with impaired affective control in mood and anxiety disorders. Our results highlight how dimensional traits may increase vulnerability for these disorders.

Gray Matter Abnormalities of Orbitofrontal Cortex and Striatum in Drug-Naïve Adult Patients With Obsessive-Compulsive Disorder

Objective: This study examined whether obsessive-compulsive disorder (OCD) patients have gray matter abnormalities in regions related to executive function, and whether such abnormalities are associated with impaired executive function.Methods: Multiple scales were administered to 27 first-episode drug-naïve OCD patients and 29 healthy controls. Comprehensive brain morphometric indicators of orbitofrontal cortex (OFC) and three striatum areas (caudate, putamen, and pallidum) were determined. Hemisphere lateralization index was calculated for each region of interest. Correlations between lateralization index and psychological variables were examined in OCD group.Results: The OCD group had greater local gyrification index for the right OFC and greater gray matter volumes of the bilateral putamen and left pallidum than healthy controls. They also had weaker left hemisphere superiority for local gyrification index of the OFC and gray matter volume of the putamen, but stronger left hemisphere superiority for gray matter volume of the pallidum. Patients' lateralization index for local gyrification index of the OFC correlated negatively with Yale-Brown Obsessive Compulsive Scale and Dysexecutive Questionnaire scores, respectively.Conclusion: Structural abnormalities of the bilateral putamen, left pallidum, and right OFC may underlie OCD pathology. Abnormal lateralization in OCD may contribute to the onset of obsessive-compulsive symptoms and impaired executive function.

Novel Volumetric and Surface-Based Magnetic Resonance Indices of the Aging Brain – Does Male and Female Brain Age in the Same Way?

Introduction: Novel post-processing methods allow not only for assessment of brain volumetry or cortical thickness based on magnetic resonance imaging (MRI) but also for more detailed analysis of cortical shape and complexity using parameters such as sulcal depth, gyrification index, or fractal dimension. The aim of this study was to analyze changes in brain volumetry and other cortical indices during aging in men and women.Material and Methods: Material consisted of 697 healthy volunteers (aged 38–80 years; M/F, 264/443) who underwent brain MRI using a 1.5-T scanner. Voxel-based volumetry of total gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) was performed followed by assessment of cortical parameters [cortical thickness (CT), sulcal depth (SD), gyrification index (GI), and fractal dimension (FD)] in 150 atlas locations using surface-based morphometry with a region-based approach. All parameters were compared among seven age groups (grouped every 5 years) separately for men and women. Additionally, percentile curves for men and women were provided for total volumes of GM, WM, and CSF.Results: In men and women, a decrease in GM and WM volumes and an increase in CSF volume seem to progress slowly since the age of 45. In men, significant GM and WM loss as well as CSF increase start above 55 years of age, while in women, significant GM loss starts above 50 and significant WM loss as well as CSF increase above 60. CT was found to significantly decrease with aging in 39% of locations in women and in 36% of locations in men, SD was found to increase in 13.5% of locations in women and in 1.3% of locations in men, GI was decreased in 3.4% of locations in women and in 2.0% of locations in men, and FD was changed in 2.7% of locations in women compared to 2.0% in men.Conclusions: Male and female brains start aging at the similar age of 45. Compared to men, in women, the cortex is affected earlier and in the more complex pattern regarding not only cortical loss but also other alterations within the cortical shape, with relatively longer sparing of WM volume.

Neonatal valproic acid exposure produces altered gyrification related to increased parvalbumin-immunopositive neuron density with thickened sulcal floors

Valproic acid (VPA) treatment is associated with autism spectrum disorder in humans, and ferrets can be used as a model to test this; so far, it is not known whether ferrets react to developmental VPA exposure with gyrencephalic abnormalities. The current study characterized gyrification abnormalities in ferrets following VPA exposure during neonatal periods, corresponding to the late stage of cortical neurogenesis as well as the early stage of sulcogyrogenesis. Ferret pups received intraperitoneal VPA injections (200 μg/g of body weight) on postnatal days (PD) 6 and 7. BrdU was administered simultaneously at the last VPA injection. Ex vivo MRI-based morphometry demonstrated significantly lower gyrification index (GI) throughout the cortex in VPA-treated ferrets (1.265 ± 0.027) than in control ferrets (1.327 ± 0.018) on PD 20, when primary sulcogyrogenesis is complete. VPA-treated ferrets showed significantly smaller sulcal-GIs in the rostral suprasylvian sulcus and splenial sulcus but a larger lateral sulcus surface area than control ferrets. The floor cortex of the inner stratum of both the rostral suprasylvian and splenial sulci and the outer stratum of the lateral sulcus showed a relatively prominent expansion. Parvalbumin-positive neuron density was significantly greater in the expanded cortical strata of sulcal floors in VPA-treated ferrets, regardless of the BrdU-labeled status. Thus, VPA exposure during the late stage of cortical neurogenesis may alter gyrification, primarily in the frontal and parietotemporal cortical divisions. Altered gyrification may thicken the outer or inner stratum of the cerebral cortex by increasing parvalbumin-positive neuron density.

ANALYSES OF BRAIN CORTICAL CHANGES OF ALZHEIMER’S DISEASE

Alzheimer’s disease (AD) produces complicated cortical changes in gray matter (GM) of the human brain. However, alterations in the brain cortex have not been clearly addressed. In our study, a cohort of 236 cases MR data enrolled from the ADNI database was categorized into three groups of normal controls (NCs), mild cognitive impairment (MCI) and AD. The GM morphological differences were investigated among the three groups using the magnetic resonance (MR) GM characteristics of gray matter volume (GMV), cortical thickness (CT), cortical surface area (CSA) and local gyrification index (LGI) at the three levels of whole brain, bilateral hemispheres and critical brain regions. Totally, there were six critical brain regions for GMV, 11 for CT, 2 for CSA and 59 for LGI among the three groups for the no-division groups. Also, there were 11 critical brain regions for GMV, 15 for CT, 8 for CSA, 3 for LGI for female sub-groups and 4 critical brain regions for GMV, 11 for CT, 1 for CSA, 3 for LGI for male sub-groups. The four measured cortical characteristics showed reliable capability in the morphological description of GM changes of AD. In conclusion, the cortical characteristics of GMV, CT, CSA and LGI of critical brain regions showed valuable indications for GM changes of AD, and those characteristics could be used as imaging markers for AD prediction.

The influence of biophysical parameters in a biomechanical model of cortical folding patterns

Abnormal cortical folding patterns, such as lissencephaly, pachygyria and polymicrogyria malformations, may be related to neurodevelopmental disorders. In this context, computational modeling is a powerful tool to provide a better understanding of the early brain folding process. Recent studies based on biomechanical modeling have shown that mechanical forces play a crucial role in the formation of cortical convolutions. However, the effect of biophysical parameters in these models remain unclear. In this paper, we investigate the effect of the cortical growth, the initial geometry and the initial cortical thickness on folding patterns. In addition, we not only use several descriptors of the folds such as the dimensionless mean curvature, the surface-based three-dimensional gyrification index and the sulcal depth, but also propose a new metric to quantify the folds orientation. The results demonstrate that the cortical growth mode does almost not affect the complexity degree of surface morphology; the variation in the initial geometry changes the folds orientation and depth, and in particular, the slenderer the shape is, the more folds along its longest axis could be seen and the deeper the sulci become. Moreover, the thinner the initial cortical thickness is, the higher the spatial frequency of the folds is, but the shallower the sulci become, which is in agreement with the previously reported effects of cortical thickness.

Morphometric Analysis of Brain in Newborn with Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) is a severe pediatric disorder with herniation of abdominal viscera into the thoracic cavity. Since neurodevelopmental impairment constitutes a common outcome, we performed morphometric magnetic resonance imaging (MRI) analysis on CDH infants to investigate cortical parameters such as cortical thickness (CT) and local gyrification index (LGI). By assessing CT and LGI distributions and their correlations with variables which might have an impact on oxygen delivery (total lung volume, TLV), we aimed to detect how altered perfusion affects cortical development in CDH. A group of CDH patients received both prenatal (i.e., fetal stage) and postnatal MRI. From postnatal high-resolution T2-weighted images, mean CT and LGI distributions of 16 CDH were computed and statistically compared to those of 13 controls. Moreover, TLV measures obtained from fetal MRI were further correlated to LGI. Compared to controls, CDH infants exhibited areas of hypogiria within bilateral fronto-temporo-parietal labels, while no differences were found for CT. LGI significantly correlated with TLV within bilateral temporal lobes and left frontal lobe, involving language- and auditory-related brain areas. Although the causes of neurodevelopmental impairment in CDH are still unclear, our results may suggest their link with altered cortical maturation and possible impaired oxygen perfusion.

Association of Gyrification Pattern, White Matter Changes, and Phenotypic Profile in Patients With Parkinson Disease

Objective:To investigate the cortical gyrification changes as well as their relationships with white matter (WM) microstructural abnormalities in the akinetic-rigid (AR) and tremor-dominant (TD) subtypes of Parkinson’s disease (PD).Methods:Sixty-four patients with the AR subtype, 26 patients with the TD subtype and 56 healthy controls (HCs) were included in this study. High-resolution T1-weighted and diffusion-weighted images were acquired for each participant. We computed local gyrification index (LGI) and fractional anisotropy (FA) to identify the cortical gyrification and WM microstructural changes in the AR and TD subtypes.Results:Compared with HCs, patients with the AR subtype showed decreased LGI in the precentral, postcentral, inferior and superior parietal, middle and superior frontal/temporal, anterior and posterior cingulate, orbitofrontal, supramarginal, precuneus, and some visual cortices, and decreased FA in the corticospinal tract, inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, forceps minor/major, and anterior thalamic radiation. Decreases in LGI and FA of the AR subtype were found to be tightly coupled. LGIs of the left inferior and middle frontal gyrus correlated with the mini-mental state examination and the Hoehn and Yahr scores of patients with the AR subtype. Patients with the TD subtype showed no significant change in the LGI and FA compared with patients with the AR subtype and HCs.Conclusions:Our results suggest that cortical gyrification changes in PD are motor phenotype-specific and are possibly mediated by the microstructural abnormalities of the underlying WM tracts.

Reduced cortical gyrification in the posteromedial cortex in unaffected relatives of schizophrenia patients with high genetic loading

Although abnormal cortical gyrification has been consistently reported in patients with schizophrenia, whether gyrification abnormalities reflect a genetic risk for the disorder remains unknown. This study investigated differences in cortical gyrification between unaffected relatives (URs) with high genetic loading for schizophrenia and healthy controls (HCs) to identify potential genetic vulnerability markers. A total of 50 URs of schizophrenia patients and 50 matched HCs underwent T1-weighted magnetic resonance imaging to compare whole-brain gyrification using the local gyrification index (lGI). Then, the lGI clusters showing significant differences were compared between the UR subgroups based on the number of first-degree relatives with schizophrenia to identify the effect of genetic loading on cortical gyrification changes. The URs exhibited significantly lower cortical gyrification than the HCs in clusters including medial parieto-occipital and cingulate regions comprising the bilateral precuneus, cuneus, pericalcarine, lingual, isthmus cingulate, and posterior cingulate gyri. Moreover, URs who had two or more first-degree relatives with schizophrenia showed greater gyrification reductions in these clusters than those who had at least one first-degree relative with schizophrenia. Our findings of reduced gyrification in URs, which are consistent with accumulated evidence of hypogyria observed in regions showing patient-control differences in previous studies, highlight that such hypogyria in posteromedial regions may serve as a genetic vulnerability marker and reflect early neurodevelopmental abnormalities resulting from a genetic risk for schizophrenia.