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Valk S.L.,Max Planck Institute for Human Cognitive and Brain Sciences | Di Martino A.,NYU Langone Medical Center | Milham M.P.,Child Mind Institute | Milham M.P.,Nathan S Kline Institute For Psychiatry Research | And 2 more authors.
Human Brain Mapping | Year: 2015

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions primarily characterized by abnormalities in social cognition. Abundant previous functional MRI studies have shown atypical activity in networks encompassing medial prefrontal cortex (mPFC) and medial parietal regions corresponding to posterior cingulate cortex and precuneus (PCC/PCU). Conversely, studies assessing structural brain anomalies in ASD have been rather inconsistent. The current work evaluated whether structural changes in ASD can be reliability detected in a large multicenter dataset. Our comprehensive structural MRI framework encompassed cortical thickness mapping and structural covariance analysis based on three independent samples comprising individuals with ASD and controls (n=220), selected from the Autism Brain Imaging Data Exchange open-access database. Surface-based analysis revealed increased cortical thickness in ASD relative to controls in mPFC and lateral prefrontal cortex. Clusters encompassing mPFC were embedded in altered inter-regional covariance networks, showing decreased covariance in ASD relative to controls primarily to PCC/PCU and inferior parietal regions. Cortical thickness increases and covariance reductions in ASD were consistent, yet of variable effect size, across the different sites evaluated and measurable both in children and adults. Our multisite study shows regional and network-level structural alterations in mPFC in ASD that, possibly, relate to atypical socio-cognitive functions in this condition. © 2015 Wiley Periodicals, Inc. Source

Zhou Y.,Biomedical Imaging Center | Lui Y.W.,Biomedical Imaging Center | Zuo X.-N.,CAS Institute of Psychology | Milham M.P.,Child Mind Institute | And 3 more authors.
Journal of Magnetic Resonance Imaging | Year: 2014

Purpose To examine thalamic and cortical injuries using fractional amplitude of low-frequency fluctuations (fALFFs) and functional connectivity MRI (fcMRI) based on resting state (RS) and task-related fMRI in patients with mild traumatic brain injury (MTBI). Materials and Methods Twenty-seven patients and 27 age-matched controls were recruited the 3 Tesla fMRI at RS and finger tapping task were used to assess fALFF and fcMRI patterns. fALFFs were computed with filtering (0.01-0.08 Hz) and scaling after preprocessing. fcMRI was performed using a standard seed-based correlation method, and delayed fcMRI (coherence) in frequency domain were also performed between thalamus and cortex. Results In comparison with controls, MTBI patients exhibited significantly decreased fALFFs in the thalamus (and frontal/temporal subsegments) and cortical frontal and temporal lobes; as well as decreased thalamo-thalamo and thalamo-frontal/ thalamo-temporal fcMRI at rest based on RS-fMRI (corrected P < 0.05). This thalamic and cortical disruption also existed at task-related condition in patients. Conclusion The decreased fALFFs (i.e., lower neuronal activity) in the thalamus and its segments provide additional evidence of thalamic injury in patients with MTBI. Our findings of fALFFs and fcMRI changes during motor task and resting state may offer insights into the underlying cause and primary location of disrupted thalamo-cortical networks after MTBI. Copyright © 2013 Wiley Periodicals, Inc. Source

Opitz A.,University of Gottingen | Opitz A.,Nathan Kline Institute for Psychiatric Research | Opitz A.,Child Mind Institute | Paulus W.,University of Gottingen | And 5 more authors.
NeuroImage | Year: 2015

Transcranial direct current stimulation (tDCS) causes a complex spatial distribution of the electric current flow in the head which hampers the accurate localization of the stimulated brain areas. In this study we show how various anatomical features systematically shape the electric field distribution in the brain during tDCS. We constructed anatomically realistic finite element (FEM) models of two individual heads including conductivity anisotropy and different skull layers. We simulated a widely employed electrode montage to induce motor cortex plasticity and moved the stimulating electrode over the motor cortex in small steps to examine the resulting changes of the electric field distribution in the underlying cortex. We examined the effect of skull thickness and composition on the passing currents showing that thinner skull regions lead to higher electric field strengths. This effect is counteracted by a larger proportion of higher conducting spongy bone in thicker regions leading to a more homogenous current over the skull. Using a multiple regression model we could identify key factors that determine the field distribution to a significant extent, namely the thicknesses of the cerebrospinal fluid and the skull, the gyral depth and the distance to the anode and cathode. These factors account for up to 50% of the spatial variation of the electric field strength. Further, we demonstrate that individual anatomical factors can lead to stimulation "hotspots" which are partly resistant to electrode positioning. Our results give valuable novel insights in the biophysical foundation of tDCS and highlight the importance to account for individual anatomical factors when choosing an electrode montage © 2015 Elsevier Inc. Source

Yang B.-Z.,Yale University | Zhang H.,Yale University | Ge W.,Yale University | Weder N.,Child Mind Institute | And 6 more authors.
American Journal of Preventive Medicine | Year: 2013

Background: Child abuse is highly prevalent and associated with increased risk for a range of health problems, including cancer, cardiovascular disease, diabetes, psychiatric disorders, and other health problems. Little is currently known about the mechanism by which early adversity confers risk for health problems later in life. Purpose: To determine if there are epigenetic differences associated with child maltreatment that may help explain association between adverse childhood experiences and later health problems. Methods: As part of a study examining genetic and environmental factors associated with depression, saliva DNA specimens were collected on 96 maltreated children removed from their parents due to abuse or neglect and 96 demographically matched control children between 2003 and 2010. In 2011, the Illumina 450K BeadChip was used on stored DNA specimens and analyzed to examine whole-genome methylation differences between maltreated and control children. Results: After controlling for multiple comparisons, maltreated and control children had significantly different methylation values at 2868 CpG sites (p<5.0 × 10-7, all sites; average methylation difference per site=17%; range=1%-62%). The gene set contained numerous markers of diseases and biological processes related to the health problems associated with early childhood adversity. Conclusions: Although replication is required, this study suggests that epigenetic mechanisms may be associated with risk for health problems later in life in maltreated children. This study lays the groundwork for future studies examining health and methylation measures to further characterize the role of epigenetic mechanisms in conferring risk for medical problems in individuals with histories of early adversity. © 2013 American Journal of Preventive Medicine. Source

Fein D.,University of Connecticut | Barton M.,University of Connecticut | Eigsti I.-M.,University of Connecticut | Kelley E.,Queens University | And 8 more authors.
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2013

Background: Although autism spectrum disorders (ASDs) are generally considered lifelong disabilities, literature suggests that a minority of individuals with an ASD will lose the diagnosis. However, the existence of this phenomenon, as well as its frequency and interpretation, is still controversial: were they misdiagnosed initially, is this a rare event, did they lose the full diagnosis, but still suffer significant social and communication impairments or did they lose all symptoms of ASD and function socially within the normal range? Methods: The present study documents a group of these optimal outcome individuals (OO group, n = 34) by comparing their functioning on standardized measures to age, sex, and nonverbal IQ matched individuals with high-functioning autism (HFA group, n = 44) or typical development (TD group, n = 34). For this study, 'optimal outcome' requires losing all symptoms of ASD in addition to the diagnosis, and functioning within the nonautistic range of social interaction and communication. Domains explored include language, face recognition, socialization, communication, and autism symptoms. Results: Optimal outcome and TD groups' mean scores did not differ on socialization, communication, face recognition, or most language subscales, although three OO individuals showed below-average scores on face recognition. Early in their development, the OO group displayed milder symptoms than the HFA group in the social domain, but had equally severe difficulties with communication and repetitive behaviors. Conclusions: Although possible deficits in more subtle aspects of social interaction or cognition are not ruled out, the results substantiate the possibility of OO from autism spectrum disorders and demonstrate an overall level of functioning within normal limits for this group. © 2013 Association for Child and Adolescent Mental Health. Source

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