News and Commentary Archive

Explore recent scientific discoveries and news as well as CLBB events, commentary, and press.

Mission

The speed of technology in neuroscience as it impacts ethical and just decisions in the legal system needs to be understood by lawyers, judges, public policy makers, and the general public. The Massachusetts General Hospital Center for Law, Brain, and Behavior is an academic and professional resource for the education, research, and understanding of neuroscience and the law. Read more

Reciprocal White Matter Alterations Due to 16p11.2 Chromosomal Deletions Versus Duplications

By Yi Shin Chang, Julia P. Owen, Nicholas J. Pojman, Tony Thieu, Polina Bukshpun, Mari L.J. Wakahiro, Elysa J. Marco, Jeffrey I. Berman, John E. Spiro, Wendy K. Chung, Randy L. Buckner, Timothy P.L. Roberts, Srikantan S. Nagarajan, Elliott H. Sherr, and Pratik Mukherjee | Human Brain Mapping | May 24, 2016

Abstract:

Copy number variants at the 16p11.2 chromosomal locus are associated with several neuropsychiatric disorders, including autism, schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, and speech and language disorders. A gene dosage dependence has been suggested, with 16p11.2 deletion carriers demonstrating higher body mass index and head circumference, and 16p11.2 duplication carriers demonstrating lower body mass index and head circumference. Here, we use diffusion tensor imaging to elucidate this reciprocal relationship in white matter organization, showing widespread increases of fractional anisotropy throughout the supratentorial white matter in pediatric deletion carriers and, in contrast, extensive decreases of white matter fractional anisotropy in pediatric and adult duplication carriers. We find associations of these white matter alterations with cognitive and behavioral impairments. We further demonstrate the value of imaging metrics for characterizing the copy number variant phenotype by employing linear discriminant analysis to predict the gene dosage status of the study subjects. These results show an effect of 16p11.2 gene dosage on white matter microstructure, and further suggest that opposite changes in diffusion tensor imaging metrics can lead to similar cognitive and behavioral deficits. Given the large effect sizes found in this study, our results support the view that specific genetic variations are more strongly associated with specific brain alterations than are shared neuropsychiatric diagnoses.

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Relationship between M100 Auditory Evoked Response and Auditory Radiation Microstructure in 16p11.2 Deletion and Duplication Carriers

By J.I. BermanD. ChudnovskayaL. BlaskeyE. KuschnerP. MukherjeeR. BucknerS. NagarajanW.K. ChungE.H. Sherr and T.P.L. Roberts | American Journal of Neuroradiology | February 11, 2016

Abstract:

BACKGROUND AND PURPOSE: Deletion and duplication of chromosome 16p11.2 (BP4–BP5) have been associated with developmental disorders such as autism spectrum disorders, and deletion subjects exhibit a large (20-ms) delay of the auditory evoked cortical response as measured by magnetoencephalography (M100 latency). The purpose of this study was to use a multimodal approach to test whether changes in white matter microstructure are associated with delayed M100 latency.

MATERIALS AND METHODS: Thirty pediatric deletion carriers, 9 duplication carriers, and 39 control children were studied with both magnetoencephalography and diffusion MR imaging. The M100 latency and auditory system DTI measures were compared between groups and tested for correlation.

RESULTS: In controls, white matter diffusivity significantly correlated with the speed of the M100 response. However, the relationship between structure and function appeared uncoupled in 16p11.2 copy number variation carriers. The alterations to auditory system white matter microstructure in the 16p11.2 deletion only partially accounted for the 20-ms M100 delay. Although both duplication and deletion groups exhibit abnormal white matter microstructure, only the deletion group has delayed M100 latency.

CONCLUSIONS: These results indicate that gene dosage impacts factors other than white matter microstructure, which modulate conduction velocity.

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Sexual Dimorphic Abnormalities in White Matter Geometry Common to Schizophrenia and Non-Psychotic High-Risk Subjects: Evidence for a Neurodevelopmental Risk Marker?

By Peter Savadjiev, Larry J. Seidman, Heidi Thermenos, Matcheri Keshavan, Susan Whitfield-Gabrieli, Tim J. Crow and Marek Kubicki | Human Brain Mapping | October 15, 2015

Abstract:

The characterization of neurodevelopmental aspects of brain alterations require neuroimaging methods that reflect correlates of neurodevelopment, while being robust to other progressive pathological processes. Newly developed neuroimaging methods for measuring geometrical features of the white matter fall exactly into this category. Our recent work shows that such features, measured in the anterior corpus callosum in diffusion MRI data, correlate with psychosis symptoms in patients with adolescent onset schizophrenia and subside a reversal of normal sexual dimorphism. Here, we test the hypothesis that similar developmental deviations will also be present in nonpsychotic subjects at familial high risk (FHR) for schizophrenia, due to genetic predispositions. Demonstrating such changes would provide a strong indication of neurodevelopmental deviation extant before, and independent of pathological changes occurring after disease onset. We examined the macrostructural geometry of corpus callosum white matter in diffusion MRI data of 35 non-psychotic subjects with genetic (familial) risk for schizophrenia, and 26 control subjects, both male and female. We report a reversal of normal sexual dimorphism in callosal white matter geometry consistent with recent results in adolescent onset schizophrenia. This pattern may be indicative of an error in neurogenesis and a possible trait marker of schizophrenia.

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