Neuroscience
-
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.
-
Stress is an additive factor in the development of depressive-like profiles that mainly onsets during adolescence. However, effects of early post-weaning stress on developing brain neurochemical pathways in inducing anxiety- and depressive-like profiles in vulnerable females have not been extensively studied. The Wistar Kyoto (WKY) rat, a putative model of adolescent depression and stress-sensitivity could elucidate the pathophysiology of stress-related depression in vulnerability. ⋯ Medial prefrontal cortex, a still maturing brain area, exhibited increased serotonin (5-HT) metabolite (p < 0.01) and turnover rates (p < 0.01) indicative of altered/maladaptive serotonergic functioning. Nucleus accumbens (p < 0.05) and dorsal striatum (p < 0.01) also depicted increased 5-HT metabolite, with the latter also demonstrating reduced Dopamine turnover (p < 0.01) as a result of homotypic stress. Hence, female WKY rats could constitute a diathesis-stress model to study underlying mechanisms of stress-related depression.
-
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.
-
The role of the pro-inflammatory cytokine interleukin-6 (IL-6) in the etiology of stress-induced synaptic plasticity is yet unknown. We took advantage of a genetically modified mouse (TG) in which IL-6 trans-signaling via the soluble IL-6 receptor was blocked, to determine the role of IL-6 trans-signaling in the effects of a Social Defeat protocol (SD) on synaptic function of the medial prefrontal cortex (mPFC). Synaptic function in stress-sensitive (S) and stress-resilient (R) animals was studied in a mPFC slice preparation with whole-cell patch-clamp recording. ⋯ Interestingly, corner preference (measuring the intensity of social defeat) correlated positively with INMDA/IAMPA and eEPSC frequency and negatively with IAMPA/IGABA. Our results suggest that SD induces behaviorally-relevant synaptic rearrangement in mPFC circuits, part of which is IL-6 dependent. In particular, IL-6 is necessary to produce synaptic plasticity leading to stress resilience in some individuals, but to stress sensitivity in others.
-
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.