Neuroscience
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Computer-aided diagnosis has become a widely-used auxiliary tool for the diagnosis of Alzheimer's disease (AD). In this study, we developed an extreme learning machine (ELM) model to discriminate between patients with AD and normal controls (NCs) using voxel-based morphometry (VBM) obtained from magnetic resonance imaging. Support vector machine (SVM), Gaussian process regression (GPR), and partial least squares (PLS) regression were compared with the ELM model. ⋯ We applied the proposed methods to data from 58 patients with AD and 94 NCs, and achieved a classification accuracy of up to 0.96 with all classification features of the ELM model, while the results of the other three models were 0.82 (PLS), 0.79 (GPR), and 0.75 (SVM). Furthermore, the effect of VBM parameter modeling is better than texture parameter. Thus, our method was optimal in distinguishing patients with AD from NCs, and may therefore be useful for the diagnosis of AD.
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An important prerequisite for the analysis of spike synchrony in extracellular recordings is the extraction of single-unit activity from the multi-unit signal. To identify single units, potential spikes are separated with respect to their potential neuronal origins ('spike sorting'). However, different sorting algorithms yield inconsistent unit assignments, which seriously influences subsequent spike train analyses. ⋯ If the latter is less important ('clean' data) the K-Means algorithm is a better option. Our results strongly argue for the need of standardized validation procedures based on ground truth data. The recipe suggested here is simple enough to become a standard procedure.
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Activation of the M1 muscarinic acetylcholine receptor (M1R) may be an effective therapeutic approach for Alzheimer's disease (AD), dementia with Lewy bodies, and schizophrenia. Previously, the M1R/M4R agonist xanomeline was shown to improve cognitive function and exert antipsychotic effects in patients with AD and schizophrenia. However, its clinical development was discontinued because of its cholinomimetic side effects. ⋯ Other than in the orbital cortex and claustrum, TAK-071 induced similar c-Fos expression patterns. When donepezil was co-administered to increase the levels of acetylcholine, the number of TAK-071-induced c-Fos-positive cells in these brain regions was increased. TAK-071, through induction of similar neural activation as that seen with xanomeline, may produce procognitive and antipsychotic effects with improved cholinergic side effects.
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Embryonic light exposure affects similarly functional lateralization in fish and birds. While the light acts on an asymmetric habenular system during the first post fertilization hours in zebrafish, in the domestic chicks it shapes the thalamofugal visual pathway affecting the right retinal photoreceptors in the last stages before hatching. However, recent evidence has shown that also in chicks a precocial embryonic time window seems open to light action. ⋯ The perseveration of pecks directed to irrelevant elements revealed that in all chicks the right hemisphere was heavily attracted by the novel elements when tested with the left eye. When using the right eye, instead, only DK chicks attended repeatedly to distractors whereas LL and EL chicks showed a left hemisphere advantage for fine discrimination and sustained attention; conversely, when tested binocularly, LL chicks perseverated significantly more than both DK and EL chicks, likely compensating the distraction with the analysis carried out by both hemispheres. For the first time, we unveiled a fine graded difference between the light modulation exerted during the two time windows, adding evidence to the idea that genes and environmental factors interplay in several separate routes to the modulation of the neurodevelopment of cerebral lateralization in vertebrates.
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Neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and Alzheimer's disease (AD) involve loss of cholinergic neurons in the basal forebrain. Here, we investigate how cholinergic dysfunction impacts the frontal cortex during interval timing, a process that can be impaired in PD and AD patients. Interval timing requires participants to estimate an interval of several seconds by making a motor response, and depends on the medial frontal cortex (MFC), which is richly innervated by basal forebrain cholinergic projections. ⋯ Principal component analyses revealed no consistent changes in time-related ramping components, but did reveal changes in higher components. Taken together, these data indicate that scopolamine changes stimulus processing rather than temporal processing in the MFC. These data could help understand how cholinergic dysfunction affects cortical circuits in diseases such as PD, DLB, and AD.