Stephan Eliez

White matter structure in autism: preliminary evidence from diffusion tensor imaging.

BACKGROUNDnIndividuals with autism have severe difficulties in social communication and relationships. Prior studies have suggested that abnormal connections between brain regions important for social cognition may contribute to the social deficits seen in autism.nnnMETHODSnIn this study, we used diffusion tensor imaging to investigate white matter structure in seven male children and adolescents with autism and nine age-, gender-, and IQ-matched control subjects.nnnRESULTSnReduced fractional anisotropy (FA) values were observed in white matter adjacent to the ventromedial prefrontal cortices and in the anterior cingulate gyri as well as in the temporoparietal junctions. Additional clusters of reduced FA values were seen adjacent to the superior temporal sulcus bilaterally, in the temporal lobes approaching the amygdala bilaterally, in occipitotemporal tracts, and in the corpus callosum.nnnCONCLUSIONSnDisruption of white matter tracts between regions implicated in social functioning may contribute to impaired social cognition in autism.

Preliminary evidence of widespread morphological variations of the brain in dyslexia.

The MR images of 16 men with dyslexia and 14 control subjects were compared using a voxel-based analysis. Evidence of decreases in gray matter in dyslexic subjects, most notably in the left temporal lobe and bilaterally in the temporoparietooccipital juncture, but also in the frontal lobe, caudate, thalamus, and cerebellum, was found. Widely distributed morphologic differences affecting several brain regions may contribute to the deficits associated with dyslexia.

Factors associated with parenting stress in mothers of children with fragile X syndrome.

ABSTRACT. Whereas previous research has demonstrated elevated levels of parenting stress in parents of children with general developmental disability, there has been little investigation of stress in parents of children specifically affected by the common neurogenetic disorder fragile X syndrome (FraX). This study elucidates stress profiles in mothers of children with FraX and delineates the contribution of child characteristics, home environment, and maternal psychological functioning to specific dimensions of parental stress. Data on child, home, and family characteristics were collected from 75 families with a child affected by FraX. These characteristics were entered into multiple regression analyses with a domain or subscale of the Parenting Stress Index as the dependent variable in each analysis. The results demonstrated that aspects of child behavior, family cohesion, household income, and maternal psychopathology differentially correlate with specific dimensions of parenting stress. Determining the relative contribution of factors associated with stress will assist in the development of interventions to improve parental well-being in mothers of children with FraX.

Brain morphology in Klinefelter syndrome: extra X chromosome and testosterone supplementation.

Objective: This study focuses on variation in brain morphology associated with supernumerary X chromosome and Klinefelter syndrome (KS). Using an unselected birth cohort of KS subjects and high-resolution MRI, the authors investigated the neuroanatomic consequences of the 47,XXY karyotype in the presence and absence of exogenous testosterone supplementation. Methods: Regional brain volumes were measured in 10 subjects with KS and 10 age-matched control men. Five of the KS subjects had received testosterone supplementation since puberty (KS+T) and five had not (KS−T). Results: KS subjects showed significant (p < 0.01) reduction in left temporal lobe gray matter volumes compared with normal control subjects. Differences in left temporal gray volumes were also significant between the KS+T and KS−T groups (p < 0.01). Verbal fluency scores were significantly different between the KS+T and KS−T groups as well. Conclusion: Supernumerary X chromosome material in men is associated with a reduction in left temporal lobe gray matter, a finding that is consistent with the verbal and language deficits associated with KS. Also, relative preservation of gray matter in the left temporal region is associated with exposure to exogenous androgen during development. A history of testosterone supplementation also appears to be associated with increased verbal fluency scores in KS patients.

Converging evidence for abnormalities of the prefrontal cortex and evaluation of midsagittal structures in pediatric posttraumatic stress disorder: An MRI study

Volumetric imaging research has shown abnormal brain morphology in posttraumatic stress disorder (PTSD) when compared with control subjects. We present results on a study of brain morphology in the prefrontal cortex (PFC) and midline structures, via indices of gray matter volume and density, in pediatric PTSD. We hypothesized that both methods would demonstrate aberrant morphology in the PFC. Further, we hypothesized aberrant brainstem anatomy and reduced corpus callosum volume in children with PTSD. Twenty-four children (aged 7-14) with history of interpersonal trauma and 24 age- and gender-matched controls underwent structural magnetic resonance imaging (sMRI). Images of the PFC and midline brain structures were first analyzed using volumetric image analysis. The PFC data were then compared with whole brain voxel-based techniques using statistical parametric mapping (SPM). The PTSD group showed significantly increased gray matter volume in the right and left inferior and superior quadrants of the PFC and smaller gray matter volume in the pons and posterior vermis areas by volumetric image analysis. The voxel-by-voxel group comparisons demonstrated increased gray matter density mostly localized to ventral PFC as compared with the control group. Abnormal frontal lobe morphology, as revealed by separate-complementary image analysis methods, and reduced pons and posterior vermis areas are associated with pediatric PTSD. Voxel-based morphometry may help to corroborate and further localize data obtained by volume of interest methods in PTSD.

Prefrontal Plasticity and Stress Inoculation-Induced Resilience

Coping with mild early life stress tends to make subsequent coping efforts more effective and therefore more likely to be used as a means of arousal regulation and resilience. Here we show that this developmental learning-like process of stress inoculation increases ventromedial prefrontal cortical volumes in peripubertal monkeys. Larger volumes do not reflect increased cortical thickness but instead represent surface area expansion of ventromedial prefrontal cortex. Expansion of ventromedial prefrontal cortex coincides with increased white matter myelination inferred from diffusion tensor magnetic resonance imaging. These findings suggest that the process of coping with early life stress increases prefrontal myelination and expands a region of cortex that broadly controls arousal regulation and resilience.

Reduced brain cortical folding in schizophrenia revealed in two independent samples

The cerebral cortex is highly convoluted, and principal folding patterns are determined early in life. Degree of cortical folding in adult life may index aberrations in brain development. Results from previous studies of cortical folding in schizophrenia are inconsistent. Here we investigated cortical folding patterns in the hitherto largest sample of patients with schizophrenia drawn from two independent cohorts. Magnetic resonance imaging scans were acquired from 207 patients and 206 healthy subjects recruited to two separate research projects in Sweden and Norway. Local gyrification index (lGI) was estimated continuously across the cortex using automated methods. Group differences in lGI were analyzed using general linear models. Patients had lower lGI in three large clusters of the cortex with peak differences found in the left precentral gyrus, right middle temporal gyrus, and right precuneus. Similar, although not completely overlapping results were found when the two cohorts were analyzed separately. There were no significant interaction effects between age and diagnosis and gender and diagnosis. The finding of reduced degree of folding in large regions of the cerebral cortex across two independent samples indicates that reduced gyrification is an inherent feature of the brain pathology in schizophrenia.

Cortical folding in Broca's area relates to obstetric complications in schizophrenia patients and healthy controls

BACKGROUNDnThe increased occurrence of obstetric complications (OCs) in patients with schizophrenia suggests that alterations in neurodevelopment may be of importance to the aetiology of the illness. Abnormal cortical folding may reflect subtle deviation from normal neurodevelopment during the foetal or neonatal period. In the present study, we hypothesized that OCs would be related to cortical folding abnormalities in schizophrenia patients corresponding to areas where patients with schizophrenia display altered cortical folding when compared with healthy controls.nnnMETHODnIn total, 54 schizophrenia patients and 54 healthy control subjects underwent clinical examination and magnetic resonance image scanning on a 1.5 T scanner. Information on OCs was collected from original birth records. An automated algorithm was used to calculate a three-dimensional local gyrification index (lGI) at numerous points across the cortical mantle.nnnRESULTSnIn both schizophrenia patients and healthy controls, an increasing number of OCs was significantly related to lower lGI in the left pars triangularis (p<0.0005) in Brocas area. For five other anatomical cortical parcellations in the left hemisphere, a similar trend was demonstrated. No significant relationships between OCs and lGI were found in the right hemisphere and there were no significant case-control differences in lGI.nnnCONCLUSIONSnThe reduced cortical folding in the left pars triangularis, associated with OCs in both patients and control subjects suggests that the cortical effect of OCs is caused by factors shared by schizophrenia patients and healthy controls rather than factors related to schizophrenia alone.

Corpus callosum and posterior fossa development in monozygotic females: a morphometric MRI study of Turner syndrome

Previous neuroimaging research in Turner syndrome (TS) has indicated parietal lobe anomalies, while anomalies in other brain loci have been less well‐substantiated. This study focused on potential cerebellar abnormalities and possible disruptions of interhemispheric (parietal) callosal connections in individuals with TS. Twenty‐seven female children and adolescents with TS (mean age 13 years, SD 4 years 2 months) and 27 age‐matched female control individuals (mean age 13 years 2 months, SD 4 years 1 month) underwent MRI. Age range of all participants was 7 to 20 years. Morphometric analyses of midline brain structures were conducted using standardized, reliable methods. When compared with control participants, females with TS showed reduced areas of the genu of the corpus callosum, the pons, and vermis lobules VI–VII, and an increased area of the fourth ventricle. No group difference in intracranial area measurements was observed. The reduced area of the genu in TS may reflect compromised connectivity between inferior parietal regions. Further, cerebellar vermis hypoplasia associated with TS agrees with literature that suggests the posterior fossa as a region prone to structural alterations in the face of early developmental insult.