Identifying subtypes of mild cognitive impairment in Parkinson’s disease using cluster analysis

Journal of Neurology - The concept of Mild Cognitive Impairment (MCI) in Parkinson’s disease (PD) has shown the potential for identifying at-risk dementia patients. Identifying subtypes of...     

Astrocyte-T cell crosstalk regulates region-specific neuroinflammation

During multiple sclerosis (MS), an inflammatory and neurodegenerative disease of the central nervous system (CNS), symptoms, and outcomes are determined by the location of inflammatory lesions. While we and others have shown that T cell cytokines differentially regulate leukocyte entry into perivascular spaces and regional parenchymal localization in murine models of MS, the molecular mechanisms of this latter process are poorly understood. Here, we demonstrate that astrocytes exhibit region-specific responses to T cell cytokines that promote hindbrain versus spinal cord neuroinflammation. Analysis of cytokine receptor expression in human astrocytes showed region-specific responsiveness to Th1 and Th17 inflammatory cytokines. Consistent with this, human and murine astrocytes treated with these cytokines exhibit differential expression of the T cell localizing molecules VCAM-1 and CXCR7 that is both cytokine and CNS region-specific. Using in vivo models of spinal cord versus brain stem trafficking of myelin-specific T cells and astrocyte-specific deletion strategies, we confirmed that Th1 and Th17 cytokines differentially regulate astrocyte expression of VCAM-1 and CXCR7 in these locations. Finally, stereotaxic injection of individual cytokines into the hindbrain or spinal cord revealed region- and cytokine-specific modulation of localizing cue expression by astrocytes. These findings identify a role for inflammatory cytokines in mediating local astrocyte-dependent mechanisms of immune cell trafficking within the CNS during neuroinflammation.     

Childhood violence exposure and social deprivation are linked to adolescent threat and reward neural function

BackgroundChildhood adversity is, unfortunately, highly prevalent and strongly associated with later psychopathology. Recent theories posit that two dimensions of early adversity, threat and deprivation, have distinct effects on brain development. The current study evaluated whether violence exposure (threat) and social deprivation (deprivation) were associated with adolescent amygdala and ventral striatum activation, respectively, in a prospective, well-sampled, longitudinal cohort using a pre-registered, open science approach.MethodsOne hundred and sixty-seven adolescents from the Fragile Families and Child Wellbeing Study completed functional magnetic resonance imaging (fMRI) scanning. Prospective longitudinal data from ages 3, 5 and 9 years were used to create indices of childhood violence exposure and social deprivation. We evaluated whether these dimensions were associated with adolescent brain function in response to threatening and rewarding faces.ResultsChildhood violence exposure was associated with decreased amygdala habituation (i.e. more sustained activation) and activation to angry faces in adolescence, whereas childhood social deprivation was associated with decreased ventral striatum activation to happy faces in adolescence. These associations held when adjusting for the other dimension of adversity (e.g., adjusting for social deprivation when examining associations with violence exposure), the interaction of the two dimensions of adversity, gender, internalizing psychopathology, and current life stress.ConclusionsConsistent with recent theories, different forms of early adversity were associated with region-specific differences in brain activation.     

What we (Should) Talk about when we Talk about Deep Brain Stimulation and Personal Identity

Neuroethics - A number of reports have suggested that patients who undergo deep brain stimulation (DBS) may experience changes to their personality or sense of self. These reports have attracted...