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Significant evidence suggests that misfolded alpha‐synuclein (aSyn), a major component of Lewy bodies, propagates in a prion‐like manner contributing to disease progression in Parkinson's disease (PD) and other synucleinopathies. In fact, timed inoculation of M83 hemizygous mice with recombinant human aSyn preformed fibrils (PFF) has shown symptomatic deficits after substantial spreading of pathogenic alpha‐synuclein, as detected by markers for the phosphorylation of S129 of aSyn. However, whether accumulated toxicity impact human‐relevant cognitive and structural neuroanatomical measures is not fully understood. Here we performed a single unilateral striatal PFF injection in M83 hemizygous mice, and using two assays with translational potential, ex vivo magnetic resonance imaging (MRI) and touchscreen testing, we examined the combined neuroanatomical and behavioral impact of aSyn propagation. In PFF‐injected mice, we observed widespread atrophy in bilateral regions that project to or receive input from the injection site using MRI. We also identified early deficits in reversal learning prior to the emergence of motor symptoms. Our findings highlight a network of regions with related cellular correlates of pathology that follow the progression of aSyn spreading, and that affect brain areas relevant for reversal learning. Our experiments suggest that M83 hemizygous mice injected with human PFF provides a model to understand how misfolded aSyn affects human‐relevant pre‐clinical measures and suggest that these pre‐clinical biomarkers could be used to detect early toxicity of aSyn and provide better translational measures between mice and human disease. [ABSTRACT FROM AUTHOR]

Background: Abnormalities in the anterior cingulate cortex (ACC) are thought to play an important role in the pathophysiology of schizophrenia. Given regional variations in ACC structure, the present study aimed to examine ACC structural subdivisions and their relationships to treatment resistance and glutamatergic levels in schizophrenia. Methods: This study included 100 patients with schizophrenia and 52 healthy controls from 2 cohorts. We applied non-negative matrix factorization to identify accurate and stable spatial components of ACC structure. Between groups, we compared ACC structural indices in each spatial component based on treatment resistance or response and tested relationships with ACC glutamate + glutamine levels. Results: We detected reductions in cortical thickness and increases in mean diffusivity in the spatial components on the surface of the cingulate sulcus, especially in patients with treatment-resistant and clozapine-resistant schizophrenia. Notably, mean diffusivity in these components was higher in patients who did not respond to clozapine compared to those who did. Furthermore, these ACC structural alterations were related to elevated ACC glutamate + glutamine levels but not related to symptomatology or antipsychotic dose. Limitations: Sample sizes, cross-sectional findings and mixed antipsychotic status were limitations of this study. Conclusion: This study identified reproducible abnormalities in ACC structures in patients with treatment-resistant and clozapine-resistant schizophrenia. Given that these spatial components play a role in inhibitory control, the present study strengthens the notion that glutamate- related disinhibition is a common biological feature of treatment resistance in schizophrenia., Introduction Current antipsychotics fail to alleviate clinical symptoms in approximately one-third of patients with schizophrenia. (1) This subtype is termed treatment-resistant schizophrenia, which is formally defined as having an inadequate [...]

Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology.

After several decades of moderate pessimism about the enterprise of developing novel therapeutic interventions for neuropsychiatrie disorders, there has been recent progress toward the use of new treatment methods. For [...]

Although multiple sclerosis has traditionally been considered a white matter disease, extensive research documents the presence and importance of grey matter injury including cortical and deep regions. The deep grey matter exhibits a broad range of pathology and is uniquely suited to study the mechanisms and clinical relevance of tissue injury in multiple sclerosis using magnetic resonance techniques. Deep grey matter injury has been associated with clinical and cognitive disability. Recently, MRI characterization of deep grey matter properties, such as thalamic volume, have been tested as potential clinical trial end points associated with neurodegenerative aspects of multiple sclerosis. Given this emerging area of interest and its potential clinical trial relevance, the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative held a workshop and reached consensus on imaging topics related to deep grey matter. Herein, we review current knowledge regarding deep grey matter injury in multiple sclerosis from an imaging perspective, including insights from histopathology, image acquisition and post-processing for deep grey matter. We discuss the clinical relevance of deep grey matter injury and specific regions of interest within the deep grey matter. We highlight unanswered questions and propose future directions, with the aim of focusing research priorities towards better methods, analysis, and interpretation of results. [ABSTRACT FROM AUTHOR]