Neuroscience
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Fatigue in people with Multiple Sclerosis (PwMS) is a poorly understood, complex, and disabling symptom. We hypothesized that the perception of fatigue in PwMS results from increased information processing in cortical areas responsible for the perception of bodily states and decreased information processing in the cortico-basal ganglia network involved in the perception of motor performance. We investigated whether PwMS who perceive excessive fatigue would have increased resting-state functional connectivity (rsFC) between interoceptive brain areas (amygdala, anterior cingulate cortex [ACC], and insula) and decreased rsFC between cortico-basal ganglia premotor network compared to PwMS not reporting fatigue. ⋯ The Modified Fatigue Impact Scale scores were correlated with the increased rsFC between interoceptive brain areas (amygdala and insula) and decreased rsFC between cortico-basal ganglia (P < 0.01). MS-related perceived fatigue has a central cause, and it may be due to increased interoceptive brain activity (perception of bodily states). Interventions are needed to decrease fatigue and reorganize the brain circuitry.
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Targeted intracranial delivery of molecularly-specific therapies within intricate brain structures poses a formidable challenge due to the heterogeneity of neuronal phenotypes and functions. Here we report the use of an implantable, miniaturized neural drug delivery system permitting dynamic adjustment of pharmacotherapies. ⋯ Remarkably, we demonstrate that micro infusions of U-50488 into the dorsal NASh induces reward-like conditioned place preferences, whereas a mere 1 mm shift ventrally results in conditioned place aversions. The striking precision afforded by this method may prove useful in other neurotherapeutic interventions.
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Autism spectrum disorder (ASD) is a highly prevalent multifactorial disorder characterized by social deficits and stereotypies. Despite extensive research efforts, the etiology of ASD remains poorly understood. However, studies using preclinical models have identified the mechanistic target of rapamycin kinase (mTOR) signaling pathway as a key player in ASD-related features. ⋯ The review also discusses the therapeutic potential of mTOR pathway inhibitors, such as rapamycin, in mitigating ASD characteristics. These insights underscore the importance of the mTOR pathway as a target for future research and therapeutic intervention in ASD. This review innovates by bringing the convergence of disrupted mTOR signaling in preclinical models and clinical data associated with ASD.
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Essential tremor with resting tremor (rET) and tremor-dominant Parkinson's disease (tPD) share many similar clinical symptoms, leading to frequent misdiagnoses. Functional connectivity (FC) matrix analysis derived from resting-state functional MRI (Rs-fMRI) offers a promising approach for early diagnosis and for exploring FC network pathogenesis in rET and tPD. However, methods relying solely on a single connection pattern may overlook the complementary roles of different connectivity patterns, resulting in reduced diagnostic differentiation. ⋯ Compared with single-pattern GCN, our proposed MCGCN model demonstrated superior classification accuracy, underscoring the advantages of integrating multiple connectivity modes. Specifically, the model achieved an average accuracy of 88.0% for distinguishing rET from HC, 88.8% for rET from tPD, and 89.6% for tPD from HC. Our findings indicate that combining graph convolutional networks with multi-connection patterns can not only effectively discriminate between tPD, rET, and HC but also enhance our understanding of the functional network mechanisms underlying rET and tPD.