We provide an update on the current psychiatric research for DBS and TMS and what the field has learned about causal circuitry implicated in anxiety and anxiety-related disorders. Recent refinement of DBS and TMS techniques have both improved their safety and efficacy as anxiety treatments and elucidated the pathological circuitry and areas causally involved in psychiatric disease. Anxiety is a debilitating hallmark of many psychiatric disorders. A significant portion of patients do not achieve sufficient benefit from psychotherapy and medication, so other therapies are being investigated. Neuromodulation, which involves targeted stimulation of neural circuitry, is FDA cleared for obsessive compulsive disorder (OCD) and depression and is an option for some patients whose anxiety have not responded to standard therapy. Over the past several years, neuromodulation protocol and technology advancements have continued to evolve the psychiatric treatment paradigm. Transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) are two of the most extensively studied neuromodulation techniques in psychiatry.
Caroline M. O'Rourke, Robert L. Selheimer, Casey H. Halpern et al.· Current Psychiatry Reports· 0 citations
Structurally diverse tau filaments form proteinaceous aggregates in a heterogeneous group of neurodegenerative diseases called tauopathies. The factors extrinsic to the highly ordered core structure that influence tau filament stability are not well understood. Here, we found that polyubiquitinated tau filaments from Alzheimer disease and vacuolar tauopathy human brain tissue exhibit distinct seeding patterns in mice, in association with differences in tau filament ultrastructure determined by cryo-electron microscopy. Chemical modulation of the polarity of polyubiquitin adjacent to the tau core with the small molecule ubistatin B resulted in the repositioning of poorly structured densities toward positively charged residues on the highly structured core filament, leading to shifting of the protofilament-protofilament interface of certain vacuolar tauopathy tau filaments. These results suggest that the structure of tau filaments that are associated with different seeding activities in vivo can be influenced by post-translational modifications.
Ryohei Watanabe, Benjamin C. Creekmore, Nabil F. Darwich et al.· Nature Structural & Molecula...· 0 citations
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