Neuroscience
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Randomized Controlled Trial
Effects of Vortioxetine and Escitalopram on Electroencephalographic Recordings - A Randomized, Crossover Trial in Healthy Males.
The antidepressant drug vortioxetine has a multimodal action modulating neurotransmission through inhibition of the serotonin transporter and modulation of serotonin receptors. Vortioxetine has also been shown to alleviate cognitive symptoms in preclinical studies and in patients with depression. However, it is largely unclear how vortioxetine affects the brain processing in humans. ⋯ Although the global EEG changes were comparable between vortioxetine and escitalopram, subtle differences between treatment effects on the EEG in terms of effect size and regional distribution of the EEG changes were apparent. To our knowledge, the current results are the first data on how vortioxetine affects EEG in humans. The present study calls for further investigations addressing the possible electrophysiological and cognitive effects of vortioxetine.
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Growing evidence indicates that GABAergic interneurons play a pivotal role to generate brain oscillation patterns, which are fundamental for the mnemonic processing of the hippocampus. While acetylcholine (ACh) is a powerful modulator of synaptic plasticity and brain function, few studies have been focused on the role of cholinergic signaling in the regulation of GABAergic inhibitory synaptic plasticity. ⋯ These forms of iLTP are blocked by the M1 type of mAChR (MR1) or by the group I of mGluR (mGluR1/5) antagonists. These results suggest the existence of spatiotemporal cooperativity between cholinergic and glutamatergic pathways where activation of mAChR serves as a metaplastic switch making glutamatergic synapses capable to induce long-term potentiation at inhibitory synapses, that may contribute to the modulation of brain mechanisms of learning and memory.
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Review
The Interaction Between Contactin and Amyloid Precursor Protein and Its Role in Alzheimer's Disease.
Alzheimer's disease (AD) is a debilitating disease and the most common cause of dementia. As the world population ages even modest advances in therapies and preventative strategies would be of benefit. ⋯ APP is an integral membrane protein which interacts with members of the Contactin family of proteins. Here we review recent progresses in the field and discuss the physiological importance of APP-Contactin interaction, as well as their roles and contributions in the pathophysiology of AD.
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The alterations of dynamic brain functions in Alzheimer's disease (AD) remain far from well understood. In this study, using functional magnetic resonance imaging (fMRI) data, we adopted a co-activation pattern (CAP) approach, which relies on very few assumptions, to explore the differences of brain dynamics among healthy elderly, patients with early amnestic mild cognitive impairment (MCI) and patients with AD. Briefly, k-means clustering was applied to all fMRI frames from the three groups and generated a set of reproducible CAPs. ⋯ Primary findings include, for AD and MCI compared with NC, the decreased mean fraction of occurrence and persistence of DMN related CAPs, which indicates the typical DMN damage; the increased/decreased mean persistence of ventral/dorsal visual network related CAPs, which may associate with the visuospatial disorder of patients with AD pathology; the elevated transition and CAP entropies and multiple alterations of CAP transition probabilities, which imply the altered mode of information flow and lifted system uncertainty in AD brains. We also found correlations of proposed measurements to cerebrospinal fluid biomarkers and neuropsychological scores. This study verified the AD-related alteration found by traditional FC analysis, and proposed several new biomarkers which have the potential for assisting AD treatment and early diagnosis.
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High gamma activity (HGA) of verbal-memory encoding using invasive-electroencephalogram has laid the foundation for numerous studies testing the integrity of memory in diseased populations. Yet, the functional connectivity characteristics of networks subserving these memory linkages remains uncertain. ⋯ The HGA-memory network comprised regions from both the cognitive control and primary processing networks, validating that effective verbal-memory encoding requires integrating brain functions, and is not dominated by a central cognitive core. Our results demonstrate a tonic intrinsic set of functional connectivity, which provides the necessary conditions for effective, phasic, task-dependent memory encoding.