Marie Schaer

A Surface-Based Approach to Quantify Local Cortical Gyrification

The high complexity of cortical convolutions in humans is very challenging both for engineers to measure and compare it, and for biologists and physicians to understand it. In this paper, we propose a surface-based method for the quantification of cortical gyrification. Our method uses accurate 3-D cortical reconstruction and computes local measurements of gyrification at thousands of points over the whole cortical surface. The potential of our method to identify and localize precisely gyral abnormalities is illustrated by a clinical study on a group of children affected by 22q11 Deletion Syndrome, compared to control individuals.

Decreased Anterior Cingulate Volume in Combat-Related PTSD

BACKGROUND Neuroanatomical data point to functional relationships between the anterior cingulate cortex (ACC) and subcortical centers regulating fear, in particular, the amygdala. Functional brain imaging has disclosed divergent patterns of ACC activation in persons with posttraumatic stress disorder (PTSD). In addition, two preliminary structural imaging studies have found evidence of smaller ACC volume in PTSD. We explored associations between PTSD and ACC volume in a relatively large sample of adult combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed. METHODS Subjects were US military combat veterans of the Vietnam and Gulf Wars recruited from two metropolitan areas served by allied Department of Veterans Affairs PTSD treatment/research centers. Anterior cingulate cortex volume was analyzed as a function of grouping factors with and without adjustment for body size. RESULTS Posttraumatic stress disorder was associated with smaller anterior cingulate cortex volume. This effect persisted in subjects without histories of alcoholism, did not interact with cohort effects, and was not modified by adjustment for body size. CONCLUSIONS Anterior cingulate cortex volume is substantially smaller in association with combat-related PTSD, a finding broadly consistent with cingulate hypofunctionality in that disorder.

Degrees of separation: A quantitative neuroimaging meta-analysis investigating self-specificity and shared neural activation between self- and other-reflection

In functional neuroimaging studies, self-specificity has been investigated by contrasting other-relevant processing against the self. Our meta-analysis investigates self-specificity with respect to degrees of self-relatedness (SR) of the other (i.e. close and public other). Literature suggests a dorsal-ventral component of self- and other-reflection within the MPFC, which has yet to be analyzed according to varying SR, nor has it been quantified statistically. In the present meta-analysis, we pursued three main objectives. First, we conducted whole-brain ALE meta-analyses using contemporary literature analyzing self>close other and self>public other contrasts to determine self-specific regions sensitive to SR. Next, we conducted ALE and conjunction analyses of studies employing self>control, close other>control, or public other>control contrasts to determine shared regions of activation. Third, we conducted post hoc analyses to quantify any observed dorsal-ventral distinction, employing novel methodology using a surface-based coordinates system. We observed significant activation in the dACC and vACC for self>close other and self>public other, whereas anterior insula was observed only for self>public other. An MPFC dorsal-ventral distinction was observed and quantified whereby public other>control was significantly more dorsal than self>control and close other>control. Our results are discussed with regards to SR. Prospective avenues of research exploiting our methodology are proposed.

Sex differences in thickness, and folding developments throughout the cortex

While significant differences in male and female brain structures have commonly been reported, only a few studies have focused on the sex differences in the way the cortex matures over time. Here, we investigated cortical thickness maturation between the age of 6 to 30 years, using 209 longitudinally-acquired brain MRI scans. Significant sex differences in the trajectories of cortical thickness change with age were evidenced using non-linear mixed effects models. Similar statistical analyses were computed to quantify the differences between cortical gyrification changes with age in males and females. During adolescence, we observed a statistically significant higher rate of cortical thinning in females compared to males in the right temporal regions, the left temporoparietal junction and the left orbitofrontal cortex. This finding is interpreted as a faster maturation of the social brain areas in females. Concomitantly, statistically significant sex differences in cortical folding changes with age were observed only in one cluster of the right prefrontal regions, suggesting that the mechanisms underlying cortical thickness and gyrification changes with age are quite distinct. Sexual dimorphism in the developmental course of the cortical maturation may be associated with the different age of onset and clinical presentation of many psychiatric disorders between males and females.

Decreased frontal gyrification correlates with altered connectivity in children with autism

The structural correlates of functional dysconnectivity in autism spectrum disorders (ASD) have been seldom explored, despite the fact that altered functional connectivity is one of the most frequent neuropathological observations in the disorder. We analyzed cerebral morphometry and structural connectivity using multi-modal imaging for 11 children/adolescents with ASD and 11 matched controls. We estimated regional cortical and white matter volumes, as well as vertex-wise measures of cortical thickness and local Gyrification Index (lGI). Diffusion Tensor Images (DTI) were used to measure Fractional Anisotropy (FA) and tractography estimates of short- and long-range connectivity. We observed four clusters of lGI reduction in patients with ASD, three were located in the right inferior frontal region extending to the inferior parietal lobe, and one was in the right medial parieto-occipital region. Reduced volume was found in the anterior corpus callosum, along with fewer inter-hemispheric frontal streamlines. Despite the spatial correspondence of decreased gyrification and reduced long connectivity, we did not observe any significant relationship between the two. However, a positive correlation between lGI and local connectivity was present in all four clusters in patients with ASD. Reduced gyrification in the inferior fronto-parietal and posterior medial cortical regions lends support for early-disrupted cortical growth in both the mirror neuron system and midline structures responsible for social cognition. Early impaired neurodevelopment in these regions may represent an initial substrate for altered maturation in the cerebral networks that support complex social skills. We also demonstrate that gyrification changes are related to connectivity. This supports the idea that an imbalance between short- and long-range white matter tracts not only impairs the integration of information from multiple neural systems, but also alters the shape of the brain early on in autism.

Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations

Objective: To determine the spectrum of clinical, neuropsychological, and neuroradiologic features in patients with autosomal recessive primary microcephaly (MCPH) due to ASPM gene mutations. Methods: ASPM was sequenced in 52 unrelated MCPH probands. In patients with ASPM mutations, we evaluated the clinical phenotype, cognition, behavior, brain MRI, and family. Results: We found homozygous or compound heterozygous ASPM loss-of-function mutations in 11 (22%) probands and 5 siblings. The probands harbored 18 different mutations, of which 16 were new. Microcephaly was severe after 1 year of age in all 16 patients, although in 4 patients the occipital-frontal circumference (OFC) at birth was decreased by only 2 SD. The OFC Z score consistently decreased after birth. Late-onset seizures occurred in 3 patients and significant pyramidal tract involvement in 1 patient. Intellectual quotients ranged from borderline-normal to severe mental retardation. Mild motor delay was noted in 7/16 patients. Language development was delayed in all patients older than 3 years. Brain MRI (n = 12) showed a simplified gyral pattern in 9 patients and several malformations including ventricle enlargement (n = 7), partial corpus callosum agenesis (n = 3), mild cerebellar hypoplasia (n = 1), focal cortical dysplasia (n = 1), and unilateral polymicrogyria (n = 1). Non-neurologic abnormalities consisted of short stature (n = 1), idiopathic premature puberty (n = 1), and renal dysplasia (n = 1). Conclusions: We provide a detailed description of features associated with ASPM mutations. Borderline microcephaly at birth, borderline-normal intellectual efficiency, and brain malformations can occur in ASPM-related primary hereditary microcephaly.

Cortical thickness, surface area, and gyrification abnormalities in children exposed to maltreatment: neural markers of vulnerability?

BACKGROUND Childhood maltreatment has been shown to significantly elevate the risk of psychiatric disorder. Previous neuroimaging studies of children exposed to maltreatment have reported atypical neural structure in several regions, including the prefrontal cortex and temporal lobes. These studies have exclusively investigated volumetric differences rather than focusing on genetically and developmentally distinct indices of brain structure. METHODS Here we used surface-based methods to examine cortical thickness, surface area, and local gyrification in a community sample of children with documented experiences of abuse (n = 22) and a group of carefully matched nonmaltreated peers (n = 21). RESULTS Reduced cortical thickness in the maltreated compared with the nonmaltreated group was observed in an extended cluster that incorporated the anterior cingulate, superior frontal gyrus, and orbitofrontal cortex. In addition, reduced cortical surface area was observed within the parcellated regions of the left middle temporal area and lingual gyrus. Local gyrification deficits within the maltreated group were located within two clusters, the lingual gyrus and the insula extending into pars opercularis. CONCLUSIONS This is the first time structural abnormalities in the anterior cingulate and lingual gyrus have been detected in children exposed to maltreatment. Surface-based methods seem to capture subtle, previously undetected, morphological abnormalities associated with maltreatment. We suggest that these approaches detect developmental precursors of brain volume differences seen in adults with histories of abuse. Because the reported regions are implicated in several clinical disorders, they might constitute biological markers of vulnerability, linking exposure to early adversity and psychiatric risk.

Abnormal patterns of cortical gyrification in velo-cardio-facial syndrome (deletion 22q11.2): An MRI study

Velo-cardio-facial syndrome (VCFS), also known as 22q11.2 deletion syndrome, is a common genetic condition associated with increased risk for developing schizophrenia. Given that cortical malformations play an integral role in the pattern of neuroanatomical alterations associated with VCFS, the aim of the present study was to quantify and localize gyral abnormalities. Magnetic resonance images were obtained on a 1.5 T scanner. The gyrification index (GI), a measure of the degree of cortical complexity, was differentially calculated for each lobe using a semi-automated protocol. The GI was calculated for 37 patients affected by VCFS as well as for 36 comparison individuals group-matched for age, handedness, and gender. The subjects affected by VCFS showed a significant decrease in the GI in the frontal and parietal lobes compared with the control group. The pattern of decreased gyrification in the frontal and parietal lobes further defines the structural changes associated with the syndrome and suggests underlying abnormalities in neural connectivity. Aberrant connectivity may be partially responsible for the cognitive and behavioral impairments in the syndrome, as well as the high incidence of schizophrenia among affected individuals.

Risk Factors and the Evolution of Psychosis in 22q11.2 Deletion Syndrome: A Longitudinal 2-Site Study

OBJECTIVE 22q11.2 Deletion syndrome (22q11.2DS) is associated with high rates of schizophrenia, other neuropsychiatric disorders, and cognitive deficits. The objectives of this 2-center study were to longitudinally assess the trajectories of psychiatric disorders in 22q11.2DS from childhood to adulthood, and to identify risk factors for their emergence. METHOD A total of 125 children and adults with 22q11.2DS were evaluated at 2 time points, baseline and follow-up (4 years apart), using standardized psychiatric and cognitive measures. RESULTS The rate of mood disorders tended to decrease during childhood and increase during late adolescence. Statistically significant predictors for the presence of a psychotic disorder as well as the severity of positive symptoms at follow-up were identical, and consisted of an anxiety disorder at baseline, lower baseline Full Scale IQ, and a greater decrease in verbal IQ scores between time points. Nine of 10 individuals with an emerging psychotic disorder had an anxiety disorder at baseline. The age of onset for a psychotic disorder was between 14 and 22 years in 82.6% of cases. CONCLUSIONS It is important to evaluate the presence of anxiety disorders in children and adolescents with 22q11.2DS, as they are major risk factors for the emergence of psychotic disorders, which usually occur during late adolescence in this at-risk population.

Congenital heart disease affects local gyrification in 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11.2DS) is a common genetic condition associated with cognitive and learning impairments. In this study, we applied a three‐dimensional method for quantifying gyrification at thousands of points over the cortical surface to imaging data from 44 children, adolescents, and young adults with 22q11.2DS (17 males, 27 females; mean age 17y 2mo [SD 9y 1mo], range 6–37y), and 53 healthy participants (21 males, 32 females; mean age 15y 4mo [SD 8y 6mo]; range 6–40y). Several clusters of reduced gyrification were observed, further substantiating the pattern of cerebral alterations presented by children with the syndrome. Comparisons within 22q11.2DS demonstrated an effect of congenital heart disease (CHD) on cortical gyrification, with reduced gyrification at the parieto‐temporo‐occipital junction in patients with CHD, as compared with patients without CHD. Reductions in gyrification can resemble mild polymicrogyria, suggesting early abnormal neuronal proliferation or migration and providing support for an effect of hemodynamic factors on brain development in 22q11.2DS. The results also shed light on the pathophysiology of acquired brain injury in other populations with CHD.