Repetitive temporal interference stimulation improves jump performance but not the postural stability in young healthy males: a randomized controlled trial.

BACKGROUND: Temporal interference (TI) stimulation, an innovative non-invasive brain stimulation technique, has the potential to activate neurons in deep brain regions. The objective of this study was to evaluate the effects of repetitive TI stimulation targeting the lower limb motor control area (i.e., the M1 leg area) on lower limb motor function in healthy individuals, which could provide evidence for further translational application of non-invasive deep brain stimulation. METHODS: In this randomized, double-blinded, parallel-controlled trial, 46 healthy male adults were randomly divided into the TI or sham group. The TI group received 2 mA (peak-to-peak) TI stimulation targeting the M1 leg area with a 20 Hz frequency difference (2 kHz and 2.02 kHz). Stimulation parameters of the sham group were consistent with those of the TI group but the current input lasted only 1 min (30 s ramp-up and ramp-down). Both groups received stimulation twice daily for five consecutive days. The vertical jump test (countermovement jump [CMJ], squat jump [SJ], and continuous jump [CJ]) and Y-balance test were performed before and after the total intervention session. Two-way repeated measures ANOVA (group × time) was performed to evaluate the effects of TI stimulation on lower limb motor function. RESULTS: Forty participants completed all scheduled study visits. Two-way repeated measures ANOVA showed significant group × time interaction effects for CMJ height (F = 8.858, p = 0.005) and SJ height (F = 6.523, p = 0.015). The interaction effect of the average CJ height of the first 15 s was marginally significant (F = 3.550, p = 0.067). However, there was no significant interaction effect on the Y balance (p > 0.05). Further within-group comparisons showed a significant post-intervention increase in the height of the CMJ (p = 0.004), SJ (p = 0.010) and the average CJ height of the first 15 s (p = 0.004) in the TI group. CONCLUSION: Repetitive TI stimulation targeting the lower limb motor control area effectively increased vertical jump height in healthy adult males but had no significant effect on dynamic postural stability.

Research on Data Analysis Network of TCM Tongue Diagnosis Based on Deep Learning Technology.

The aim of the study is to build a tongue image intelligent analysis "end-to-end" deep learning network based on a tongue diagnosis image of traditional Chinese medicine. The tongue target region in the original image was segmented by the UNet tongue segmentation model at the front end of the network. After segmentation, the feature vector of the tongue target region was extracted by the ResNet network, and then the blood pressure on the day of shooting was fused with the feature vector extracted by the ResNet network through the convolution operation method to complete the extraction of two groups of data of tongue feature and fusion feature. Based on analyzing the data of blood pressure, tongue image, and their fusion at the end of the network, four regression analysis methods were used to predict the stage mean value. After training, the model is tested with the test set data, and the test results are evaluated with mean absolute error (MAE). The prediction error of the model based on the fusion data of tongue image and blood pressure on the day of shooting was lower than that of the other two data modes. The UNet tongue segmentation model combined with the ResNet network can realize the automatic extraction of tongue image features. The extracted features combined with machine learning modeling can be used to explore the complex hierarchical mathematical association between tongue image and clinical data. The experimental results show that the multimodal data fusion method is an important way to mine the clinical value of the TCM tongue image.

Baclofen ameliorates spatial working memory impairments induced by chronic cerebral hypoperfusion via up-regulation of HCN2 expression in the PFC in rats.

Chronic cerebral hypoperfusion (CCH) causes memory deficits and increases the risk of vascular dementia (VD) through several biologically plausible pathways. However, whether CCH causes prefrontal cortex (PFC)-dependent spatial working memory impairments and Baclofen, a GABAB receptor agonist, could ameliorate the impairments is still not clear especially the mechanisms underlying the process. In this study, rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) to induce CCH. Two weeks later, rats were treated with 25mg/kg Baclofen (intraperitioneal injection, i.p.) for 3 weeks. Spatial working memory was evaluated in a Morris water maze using a modified delayed matching-to-place (DMP) procedure. Western blotting and immunohistochemistry were used to quantify the protein levels and protein localization. Our results showed that 2VO caused striking spatial working memory impairments, accompanied with a decreased HCN2 expression in PFC, but the protein levels of protein gene product 9.5 (PGP9.5, a neuron specific protein), glial fibrillary acidic protein (GFAP), synaptophysin (SYP), brain-derived neurotrophic factor (BDNF), parvalbumin (PV) and HCN1 were not distinguishably changed as compared with sham-operated rats. Baclofen treatment significantly improved the spatial working memory impairments caused by 2VO, accompanied with a reversion of 2VO-induced down-regulation of HCN2. Furthermore, there was a co-localization of HCN2 subunits and parvalbumin-positive neurons in PFC. Therefore, HCN2 may target inhibitory interneurons that is implicated in working memory processes, which may be a possible mechanism of the up-regulation of HCN2 by Baclofen treatment that reliefs spatial working memory deficits in rats with CCH.

Flupirtine attenuates chronic restraint stress-induced cognitive deficits and hippocampal apoptosis in male mice.

Chronic restraint stress (CRS) causes hippocampal neurodegeneration and hippocampus-dependent cognitive deficits. Flupirtine represents neuroprotective effects and we have previously shown that flupirtine can protect against memory impairment induced by acute stress. The present study aimed to investigate whether flupirtine could alleviate spatial learning and memory impairment and hippocampal apoptosis induced by CRS. CRS mice were restrained in well-ventilated Plexiglass tubes for 6h daily beginning from 10:00 to 16:00 for 21 consecutive days. Mice were injected with flupirtine (10mg/kg and 25mg/kg) or vehicle (10% DMSO) 30min before restraint stress for 21 days. After stressor cessation, the spatial learning and memory, dendritic spine density, injured neurons and the levels of Bcl-2, Bax, p-Akt, p-GSK-3ß, p-Erk1/2 and synaptophysin of hippocampal tissues were examined. Our results showed that flupirtine significantly prevented spatial learning and memory impairment induced by CRS in the Morris water maze. In addition, flupirtine (10mg/kg and 25mg/kg) treatment alleviated neuronal apoptosis and the reduction of dendritic spine density and synaptophysin expression in the hippocampal CA1 region of CRS mice. Furthermore, flupirtine (10mg/kg and 25mg/kg) treatment significantly decreased the expression of Bax and increased the p-Akt and p-GSK-3ß, and flupirtine (25mg/kg) treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice. These results suggested that flupirtine exerted protective effects on the CRS-induced cognitive impairment and hippocampal neuronal apoptosis, which is possibly associated with the activation of Akt/GSK-3ß and Erk1/2 signaling pathways.

Activity-dependent downregulation of M-Type (Kv7) K⁺ channels surface expression requires the activation of iGluRs/Ca²âº/PKC signaling pathway in hippocampal neuron.

M-type (Kv7) K(+) channels, encoded by KCNQ2-KCNQ5 genes, play a pivotal role in controlling neuronal excitability. However, precisely how neuronal activity regulates Kv7 channel translocation has not yet been fully defined. Here we reported activity-dependent changes in Kv7 channel subunits Kv7.2 and Kv7.3 surface expression by glutamate (glu). In the present study, we found that treatment with glutamate rapidly caused a specific decrease in M-current as well as Kv7 channel surface expression in primary cultured hippocampal neurons. The glutamate effects were mimicked by NMDA and AMPA. The glutamate effects on Kv7 channels were partially attenuated by pre-treatment of NMDA receptors antagonist d,l-APV or AMPA-KA receptors antagonist CNQX. The signal required Ca(2+) influx through L-type Ca(2+) channel and intracellular Ca(2+) elevations. PKC activation was involved in the glutamate-induced reduction of Kv7 channel surface expression. Moreover, a significant reduction of Kv7 channel surface expression occurred following glycine-induced "chem"-LTP in vitro and hippocampus-dependent behavioral learning training in vivo. These results demonstrated that activity-dependent reduction of Kv7 channel surface expression through activation of ionotropic glutamate receptors (iGluRs)/Ca(2+)/PKC signaling pathway might be an important molecular mechanism for regulation of neuronal excitability and synaptic plasticity.