Cerebral Motor Cortex Research Articles

Banxia Baizhu Tianma Decoction alleviates pentylenetetrazol-induced epileptic seizures in rats by preventing neuronal cell damage and apoptosis and altering serum and urine metabolic profiles

Ethnopharmacological relevanceEpilepsy (EP) is one of the most prevalent chronic neurological disorders in children, characterised by a prolonged course and a propensity for recurrence. Banxia Baizhu Tianma Decoction (BBTD), a traditional Chinese medicine formula, is commonly employed in the clinical management of EP and has demonstrated satisfactory therapeutic effects. Aim of the studyThis study aimed to evaluate the anti-epileptic effects of BBTD and to explore its molecular mechanisms. Materials and methodsEP rat model was induced by pentylenetetrazol (PTZ) and treated with BBTD. Parameters such as seizure grade and duration were recorded to evaluate the improvement of BBTD on epileptic behavior. Nissl staining was used to observe the pathological changes in the cerebral motor cortex. The expression levels of the Bax and Bcl-2 in the motor cortex were measured by western blot analysis to assess neuronal damage and apoptosis. The therapeutic action of BBTD was evaluated by examining the levels of neurotransmitters γ-aminobutyric acid (GABA) and glutamate (Glu) in the brain tissue of EP rats, along with assessments of neuronal damage and apoptosis. Non-targeted metabolomics techniques were employed to conduct a comprehensive analysis of serum and urine metabolites, and network analysis of metabolite-related targets was performed to enhance understanding of the anti-epileptic effects and mechanisms of BBTD. ResultsAfter BBTD treatment, the EP model rats exhibited reduced seizure severity and shortened seizure duration. Moreover, BBTD mitigated PTZ-induced neuronal damage, as evidenced by a significant increase in the number of Nissl bodies in the motor cortex following treatment. At the same time, BBTD inhibited neuronal apoptosis, as demonstrated by the up-regulation of the anti-apoptotic protein Bcl-2 and down-regulation of the pro-apoptotic protein Bax in the brain tissue of treated rats. In addition, BBTD reversed the decreased levels of GABA and the increased levels of Glu in the brain tissue of the model group. Metabolomics analyses suggested that BBTD treatment for EP may be closely associated with alterations in urinary metabolites related to vitamin B6 and pyrimidine metabolism, as well as serum metabolites involved in purine metabolism, glycerophospholipid metabolism and vitamin B6 metabolism. Finally, network analysis of metabolite targets indicated that dopamine and alpha-linolenic acid metabolites may play significant roles in the therapeutic effects of BBTD on EP. ConclusionBBTD demonstrated anti-epileptic effects in PTZ-induced seizure rats by regulating neurotransmitter balance, reducing neuronal damage and inhibiting apoptosis, suggesting its potential for the development of novel AEDs. This is the first time that UHPLC-MS-based urine and serum metabolomics have been used to elucidate the anti-epileptic mechanism of BBTD, providing insights into the underlying mechanisms of BBTD's action.

Single-cell RNA sequencing reveals peripheral immunological features in Parkinson’s Disease

Although many researchers of Parkinson’s disease (PD) have shifted their focus from the central nervous system (CNS) to the peripheral blood, a significant knowledge gap remains between PD severity and the peripheral immune response. In the current study, we aimed to map the peripheral immunity atlas in peripheral blood mononuclear cells (PBMCs) from PD patients and healthy controls using single-cell RNA sequencing (scRNA-seq). Our study employed scRNA-seq analysis to map the peripheral immunity atlas in PD by profiling PBMCs from PD-Early, PD-Late patients and matched controls. By enlarging the blood sample size, we validated the roles of NK cells in numerous immune-related biological processes. We also detected the infiltration of NK cells into the cerebral motor cortex as the disease progressed, using human brain sections, and elucidated the communication between the periphery and CNS and its implications for PD. As a result, cell subpopulation atlases in PBMCs from PD patients and healthy controls along with differentially expressed genes in NK cells were identified by scRNA-seq analysis, representing 6 major immune cell subsets among which NK cells declined in the progression of PD. We further validated NK cell reduction in increasing samples and found that they participated in numerous immune-related biological processes and infiltration into the cerebral motor cortex as the disease proceeded, evidencingd the close communication between the peripheral immune response and CNS. Strikingly, XCL2 positively correlated with PD severity, with good predictive performance of PD and specific expression in subclusters C2 and C5 of NK cells. All these findings delineated the critical role of peripheral immune response mediated by NK cells in the pathogenesis of PD. NK cell-specific XCL2 could be used as a diagnostic marker for treating PD. The indispensable function of NK cells and NK cell-specific molecular biomarkers highlighted the implication of the peripheral immune response in PD progression. Trial registration: ChiCTR, ChiCTR1900023975. Registered 20 June 2019 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=31035.

Pathology reduction and motor behavior improvement associated with ultrasound-mediated delivery of arctiin to the motor cortex in a mutant SOD1 mouse model of amyotrophic lateral sclerosis

BackgroundAmyotrophic lateral sclerosis (ALS) is marked by the deterioration of both cortical and spinal cord motor neurons. Despite the underlying causes of the disease remain elusive, there has been a growing attention on the well-being of cortical motor neurons in recent times. Focused ultrasound combined with microbubbles (FUS/MB) for opening the blood–brain barrier (BBB) provides a means for drug delivery to specific brain regions, holding significant promise for the treatment of neurological disorders. ObjectivesWe aim to explore the outcomes of FUS/MB-mediated delivery of arctiin (Arc), a natural compound with anti-inflammatory activities, to the cerebral motor cortex area by using a transgenic ALS mouse model. MethodsThe ALS mouse model with the SOD1G93A mutation was used and subjected to daily Arc administration with FUS/MB treatment twice a week. After six-week treatments, the motor performance was assessed by grip strength, wire hanging, and climbing-pole tests. Mouse brains, spinal cords and gastrocnemius muscle were harvested for histological staining. ResultsCompared with the mice given Arc administration only, the combined treatments of FUS/MB with Arc induced further mitigation of the motor function decline, accompanied by improved health of the gastrocnemius muscle. Furthermore, notable neuroprotective effect was evidenced by the amelioration of motor neuron failure in the cortex and lumbar spinal cord. ConclusionThese preliminary results indicated that the combined treatment of FUS/MB and arctiin exerted a potentially beneficial effect on neuromuscular function in the ALS disease.

Neuronal Circuit Dysfunction in Amyotrophic Lateral Sclerosis.

The primary neural circuit affected in Amyotrophic Lateral Sclerosis (ALS) patients is the corticospinal motor circuit, originating in upper motor neurons (UMNs) in the cerebral motor cortex which descend to synapse with the lower motor neurons (LMNs) in the spinal cord to ultimately innervate the skeletal muscle. Perturbation of these neural circuits and consequent loss of both UMNs and LMNs, leading to muscle wastage and impaired movement, is the key pathophysiology observed. Despite decades of research, we are still lacking in ALS disease-modifying treatments. In this review, we document the current research from patient studies, rodent models, and human stem cell models in understanding the mechanisms of corticomotor circuit dysfunction and its implication in ALS. We summarize the current knowledge about cortical UMN dysfunction and degeneration, altered excitability in LMNs, neuromuscular junction degeneration, and the non-cell autonomous role of glial cells in motor circuit dysfunction in relation to ALS. We further highlight the advances in human stem cell technology to model the complex neural circuitry and how these can aid in future studies to better understand the mechanisms of neural circuit dysfunction underpinning ALS.

Mechanosensitive Ion Channels Piezo1 and Piezo2 Mediate Motor Responses In Vivo During Transcranial Focused Ultrasound Stimulation of the Rodent Cerebral Motor Cortex.

Transcranial focused ultrasound (tFUS) neuromodulation offers a noninvasive, safe, deep brain stimulation with high precision, presenting potential in understanding neural circuits and treating brain disorders. This in vivo study investigated the mechanism of tFUS in activating the opening of the mechanosensitive ion channels Piezo1 and Piezo2 in the mouse motor cortex to induce motor responses. Piezo1 and Piezo2 were knocked down separately in the mouse motor cortex, followed by EMG and motor cortex immunofluorescence comparisons before and after knockdown under tFUS stimulation. The results demonstrated that the stimulation-induced motor response success rates in Piezo knockdown mice were lower compared to the control group (Piezo1 knockdown: 57.63% ± 14.62%, Piezo2 knockdown: 73.71% ± 13.10%, Control mice: 85.69% ± 10.23%). Both Piezo1 and Piezo2 knockdowns showed prolonged motor response times (Piezo1 knockdown: 0.62 ± 0.19 s, Piezo2 knockdown: 0.60 ± 0.13 s, Control mice: 0.44 ± 0.12 s) compared to controls. Additionally, Piezo knockdown animals subjected to tFUS showed reduced immunofluorescent c-Fos expression in the target area when measured in terms of cells per unit area compared to the control group. This in vivo study confirms the pivotal role of Piezo channels in tFUS-induced neuromodulation, highlighting their influence on motor response efficacy and timing. This study provides insights into the mechanistic underpinnings of noninvasive brain stimulation techniques and opens avenues for developing targeted therapies for neural disorders.

Cerebral Palsy: A Narrative Review on Childhood Disorder.

Cerebral palsy, one of the most common reasons for infirmity in children and young people in developed countries, refers to several neurological diseases that impact movement and coordination. Central nervous system damage received during the first stages of brain development can cause cerebral palsy, a non-progressive condition that manifests as impairments of movement and posture. Two cases per 1000 are reported, and the causes include those mentioned for high-risk infants. Mental retardation, sensory deficiencies, failure to thrive, seizures, and behavioral or emotional issues are some of the associated difficulties. To enable interdisciplinary intervention, early identification is crucial. The result varies depending on the topography, severity, and presence of concomitant abnormalities in cerebral palsy. Cerebral palsy is caused by a static injury to the cerebral motor cortex that happens before, during, or within five years after birth. Various circumstances can influence the disease, including cerebral anoxia, cerebral hemorrhage, infection, and hereditary disorders. Interventions for children are typically provided as part of multidisciplinary rehabilitation programs.Musculoskeletal complaints are common, and pain is a significant underreported symptom.

A monocarboxylate transporter-dependent mechanism confers resistance to exercise-induced fatigue in a high-altitude hypoxic environment

The body is more prone to fatigue in a high-altitude hypoxic environment, in which fatigue occurs in both peripheral muscles and the central nervous system (CNS). The key factor determining the latter is the imbalance in brain energy metabolism. During strenuous exercise, lactate released from astrocytes is taken up by neurons via monocarboxylate transporters (MCTs) as a substrate for energy metabolism. The present study investigated the correlations among the adaptability to exercise-induced fatigue, brain lactate metabolism and neuronal hypoxia injury in a high-altitude hypoxic environment. Rats were subjected to exhaustive incremental load treadmill exercise under either normal pressure and normoxic conditions or simulated high-altitude, low-pressure and hypoxic conditions, with subsequent evaluation of the average exhaustive time as well as the expression of MCT2 and MCT4 in the cerebral motor cortex, the average neuronal density in the hippocampus, and the brain lactate content. The results illustrate that the average exhaustive time, neuronal density, MCT expression and brain lactate content were positively correlated with the altitude acclimatization time. These findings demonstrate that an MCT-dependent mechanism is involved in the adaptability of the body to central fatigue and provide a potential basis for medical intervention for exercise-induced fatigue in a high-altitude hypoxic environment.

Monocarboxylate transporter-dependent mechanism is involved in the adaptability of the body to exercise-induced fatigue under high-altitude hypoxia environment

Under high-altitude hypoxia environment, the body is more prone to fatigue, which occurs in both peripheral muscles and the central nervous system (CNS). The key factor determining the latter is the imbalance of brain energy metabolism, which makes it difficult to maintain the central nervous system to send peripheral nerve impulse continuously. During strenuous exercise, lactate released from astrocytes is taken up by neurons stored for energy to maintain synaptic transmission, a process mediated by monocarboxylate transporters (MCTs) in CNS. The present study investigated the correlation among the adaptability to exercise-induced fatigue, brain lactate metabolism and neuronal hypoxia injury under high-altitude hypoxia environment. Rats were subjected to exhaustive incremental load treadmill exercise under either normal pressure and normoxic conditions or simulated high-altitude low pressure and hypoxic conditions, with subsequent evaluation of the average exhaustive time as well as the expression of monocarboxylate transporters 2 (MCT2), MCT4, the average neuronal density in the cerebral motor cortex, and the lactate content in rat brain. At the early stage of simulated high-altitude environment, the average exhaustive time and neuronal density of rats decreased rapidly, then gradually recovered to some extent with the extension of altitude acclimatization time. The expression of MCT2, MCT4 and the lactate content in rat brain also increased gradually with the extension of altitude acclimatization time. After the application of lactate transport inhibitor, the recovery of exercise capacity of rats after altitude acclimatization was quickly blocked, and the neuronal injury in the cerebral motor cortex of rats was also significantly aggravated. These findings demonstrate that MCT-dependent mechanism is involved in the adaptability of the body to central fatigue, and provide a potential basis for medical intervention for exercise-induced fatigue under high-altitude hypoxia environment.

Inhibition of VEGFR-2 by SU5416 increases neonatally glutamate-induced neuronal damage in the cerebral motor cortex and hippocampus.

Vascular endothelial growth factor (VEGF) exerts neuroprotective or proinflammatory effects, depending on what VEGF forms (A-E), receptor types (VEGFR1-3), and intracellular signaling pathways are involved. Neonatal monosodium glutamate (MSG) treatment triggers neuronal death by excitotoxicity, which is commonly involved in different neurological disorders, including neurodegenerative diseases. This study was designed to evaluate the effects of VEGFR-2 inhibition on neuronal damage triggered by excitotoxicity in the cerebral motor cortex (CMC) and hippocampus (Hp) after neonatal MSG treatment. MSG was administered at a dose of 4 g/kg of body weight (b.w.) subcutaneously on postnatal days (PD) 1, 3, 5, and 7, whereas the VEGFR-2 inhibitor SU5416 was administered at a dose of 10 mg/kg b.w. subcutaneously on PD 5 and 7, 30 min before the MSG treatment. Neuronal damage was assessed using hematoxylin and eosin staining, fluoro-Jade staining, and TUNEL assay. Additionally, western blot assays for some proteins of the VEGF-A/VEGFR-2 signaling pathway (VEGF-A, VEGFR-2, PI3K, Akt, and iNOS) were carried out. All assays were performed on PD 6, 8, 10, and 14. Inhibition of VEGFR-2 signaling by SU5416 increases the neuronal damage induced by neonatal MSG treatment in both the CMC and Hp. Moreover, neonatal MSG treatment increased the expression levels of the studied VEGF-A/VEGFR-2 signaling pathway proteins, particularly in the CMC. We conclude that VEGF-A/VEGFR-2 signaling pathway activation could be part of the neuroprotective mechanisms that attempt to compensate for neuronal damage induced by neonatal MSG treatment and possibly also in other conditions involving excitotoxicity.

Enhancement of motor imagery training efficiency by an online adaptive training paradigm integrated with error related potential

Objective. Motor imagery (MI) is a process of autonomously modulating the motor area to rehearse action mentally without actual execution. Based on the neuroplasticity of the cerebral cortex, MI can promote the functional rehabilitation of the injured cerebral cortex motor area. However, it usually takes several days to a few months to train individuals to acquire the necessary MI ability to control rehabilitation equipment in current studies, which greatly limits the clinical application of rehabilitation training systems based on the MI brain–computer interface (BCI). Approach. A novel MI training paradigm combined with the error related potential (ErrP) is proposed, and online adaptive training of the MI classifier was performed using ErrP. ErrP is used to correct the output of the MI classification to obtain a higher accuracy of kinesthetic feedback based on the imagination intention of subjects while generating simulated labels for MI online adaptive training. In this way, we improved the MI training efficiency. Thirteen subjects were randomly divided into an experimental group using the proposed paradigm and a control group using the traditional MI training paradigm to participate in six MI training experiments. Main results. The proposed paradigm enabled the experimental group to obtain a higher event-related desynchronization modulation level in the contralateral brain region compared with the control group and 69.76% online classification accuracy of MI after three MI training experiments. The online classification accuracy reached 72.76% and the whole system recognized the MI intention of the subjects with an online accuracy of 82.61% after six experiments. Significance. Compared with the conventional unimodal MI training strategy, the proposed approach enables subjects to use the MI-BCI based system directly and achieve a better performance after only three training experiments with training left and right hands simultaneously. This greatly improves the usability of the MI-BCI-based rehabilitation system and makes it more convenient for clinical use.

Short term effects of anodal cerebellar vs. anodal cerebral transcranial direct current stimulation in stroke patients, a randomized control trial.

Balance and gait impairments are major motor deficits in stroke patients that require intensive neuro-rehabilitation. Anodal transcranial direct current stimulation is a neuro-modulatory technique recently used in stroke patients for balance and gait improvement. Majority of studies focusing on tDCS have assessed its effects on cerebral motor cortex and more recently cerebellum as well but to our best knowledge the comparison of stimulating these two regions in stroke patients is not investigated so far. The current study aimed to compare the effect of anodal transcranial direct current stimulation on cerebellar and cerebral motor cortex M1 in stroke patients. This double-blinded, parallel, randomized, sham controlled trial included 66 patients with a first-ever ischemic stroke were recruited into three groups; Cerebellar stimulation group (CbSG), M1 Stimulation Group (MSG), and Sham stimulation group (SSG). A total of three sessions of anodal transcranial direct current stimulation were given on consecutive days in addition to non-immersive virtual reality using Xbox 360 with kinect. Anodal tDCS with an intensity of 2 mA was applied for a duration of 20 min. Primary outcome measures berg balance scale (BBS), timed up and go test (TUG), BESTest Balance Evaluation-Systems Test (BESTest) and secondary outcomes measures montreal cognitive assessment (MoCA), mini mental state examination (MMSE), Johns Hopkins Fall Risk Assessment Tool (JHFRAT), twenty five feet walk test (25FWT), six minute walk test (6MWT), and tDCS Adverse Effects was assessed before initiation of treatment (T0) and at the end of third session of stimulation (T1). The results of between group's analysis using mean difference showed a significant difference with p-value <0.05 for balance (BBS, TUG, BESTest), walking ability (6MWT, 25FWT), risk of fall (JHFRAT). Cognitive function did not show any significant change among the groups for MoCA with p-value >0.05 but MMSE was improved having significant p-value (p = 0.013). However, 6MWT and 25FWT showed non-significant results for both between group and within group analysis. In pairwise comparison both the cerebellar and cerebral stimulation groups showed Significant difference with p-value <0.05 in comparison to sham stimulation; BBS (cerebellar vs. sham p ≤ 0.001, cerebral vs. sham p = 0.011), TUG (cerebellar vs. sham p = 0.001, cerebral vs. sham p = 0.041), Bestest (cerebellar vs. sham p = 0.007, cerebral vs. sham p = 0.003). Whereas for JHFRAT only cerebellar stimulation in comparison to sham and motor cortex stimulation showed significant improvements (cerebellar vs. M1 p = 0.037, cerebellar vs. sham p = 0.037). MMSE showed significant improvement in M1 stimulation (M1 vs. cerebellar p = 0.036, M1 vs. sham p = 0.011). Findings of the study suggest anodal tDCS stimulation of the cerebellum and cerebral motor cortex both improves gait, balance and risk of fall in stroke patients. However, both stimulation sites do not induce any notable improvement in cognitive function. Effects of both stimulation sites have similar effects on mobility in stroke patients.

Analysis of Functional Corticomuscular Coupling Based on Multiscale Transfer Spectral Entropy.

Functional corticomuscular coupling (FCMC) between the cerebral motor cortex and muscle activity reflects multi-layer and nonlinear interactions in the sensorimotor system. Considering the inherent multiscale characteristics of physiological signals, we proposed multiscale transfer spectral entropy (MSTSE) and introduced the unidirectionally coupled Hénon maps model to verify the effectiveness of MSTSE. We recorded electroencephalogram (EEG) and surface electromyography (sEMG) in steady-state grip tasks of 29 healthy participants and 27 patients. Then, we used MSTSE to analyze the FCMC base on EEG of the bilateral motor areas and the sEMG of the flexor digitorum superficialis (FDS). The results show that MSTSE is superior to transfer spectral entropy (TSE) method in restraining the spurious coupling and detecting the coupling more accurately. The coupling strength was higher in the β1, β2, and γ2 bands, among which, it was highest in the β1 band, and reached its maximum at the 22-30 scale. On the directional characteristics of FCMC, the coupling strength of EEG→sEMG is superior to the opposite direction in most cases. In addition, the coupling strength of the stroke-affected side was lower than that of healthy controls' right hand in the β1 and β2 bands and the stroke-unaffected side in the β1 band. The coupling strength of the stroke-affected side was higher than that of the stroke-unaffected side and the right hand of healthy controls in the sEMG→EEG direction of γ2 band. This study provides a new perspective and lays a foundation for analyzing FCMC and motor dysfunction.

Rehabilitation on a treadmill induces plastic changes in the dendritic spines of spinal motoneurons associated with improved execution after a pharmacological injury to the motor cortex in rats

Lesions to the corticospinal tract result in several neurological symptoms and several rehabilitation protocols have proven useful in attempts to direct underlying plastic phenomena. However, the effects that such protocols may exert on the dendritic spines of motoneurons to enhance accuracy during rehabilitation are unknown. Thirty three female Sprague-Dawley adult rats were injected stereotaxically at the primary motor cerebral cortex (Fr1) with saline (CTL), or kainic acid (INJ), or kainic acid and further rehabilitation on a treadmill 16 days after lesion (INJ+RB). Motor performance was evaluated with the the Basso, Beatie and Bresnahan (BBB) locomotion scale and in the Rotarod. Spine density was quantified in a primary dendrite of motoneurons in Lamina IX in the ventral horn of the thoracolumbar spinal cord as well as spine morphology. AMPA, BDNF, PSD-95 and synaptophysin expression was evaluated by Western blot. INJ+RB group showed higher scores in motor performance. Animals from the INJ+RB group showed more thin, mushroom, stubby and wide spines than the CTL group, while the content of AMPA, BDNF, PSD-95 and Synaptophysin was not different between the groups INJ+RB and CTL. AMPA and synaptophysin content was greater in INJ group than in CTL and INJ+RB groups. The increase in the proportion of each type of spine observed in INJ+RB group suggest spinogenesis and a greater capability to integrate the afferent information to motoneurons under relatively stable molecular conditions at the synaptic level.

Motor-evoked potentials after focal electrical stimulation predict drug-induced convulsion potentials in rats

Drug-induced convulsions—often caused by the inhibition of GABA receptors and stimulation of glutamate receptors—are difficult to predict in animals. In this study, we attempted to detect the proconvulsant potential using motor-evoked potentials (MEPs) after focal electrical stimulation or upon using a functional observational battery (FOB). Pentylenetetrazole, kainic acid, and pilocarpine were used as convulsion-inducing drugs, and baclofen was used as a negative control. First, each compound was administered to male rats, and the FOB tests were performed. All drugs induced behavioral changes, but no commonality was found. Single electrical stimulation train MEPs were recorded under anesthesia for 60 min (at 5 min intervals) after administration of each drug. A dose-dependent increase in MEPs was observed for each convulsion-inducing drug. Moreover, paired electrical stimulation (conditioned and test) of the cerebral motor cortex was conducted with a 1–15 ms interstimulus interval (ISI), 10 min after administration of the drug. All convulsion-inducing drugs inhibited the short-interval intracortical inhibition (ISI: 3 ms), which may be associated with GABA. Intracortical facilitation (ISI: 11 ms), related to glutamate, was not enhanced by any drug but was inhibited by pilocarpine. Dose correlation was not found in short-interval intracortical inhibition or intracortical facilitation in any drugs. No changes in MEPs were observed after baclofen administration. These results suggest that it is possible to evaluate the convulsion potential and associated mechanisms using MEP, independent of the behavioral changes. The early identification of convulsion potential using this model will lead to more efficient drug development.

Relationship between Neuronal Damage/Death and Astrogliosis in the Cerebral Motor Cortex of Gerbil Models of Mild and Severe Ischemia and Reperfusion Injury.

Neuronal loss (death) occurs selectively in vulnerable brain regions after ischemic insults. Astrogliosis is accompanied by neuronal death. It can change the molecular expression and morphology of astrocytes following ischemic insults. However, little is known about cerebral ischemia and reperfusion injury that can variously lead to damage of astrocytes according to the degree of ischemic injury, which is related to neuronal damage/death. Thus, the purpose of this study was to examine the relationship between damage to cortical neurons and astrocytes using gerbil models of mild and severe transient forebrain ischemia induced by blocking the blood supply to the forebrain for five or 15 min. Significant ischemia tFI-induced neuronal death occurred in the deep layers (layers V and VI) of the motor cortex: neuronal death occurred earlier and more severely in gerbils with severe ischemia than in gerbils with mild ischemia. Distinct astrogliosis was detected in layers V and VI. It gradually increased with time after both ischemiae. The astrogliosis was significantly higher in severe ischemia than in mild ischemia. The ischemia-induced increase of glial fibrillary acidic protein (GFAP; a maker of astrocyte) expression in severe ischemia was significantly higher than that in mild ischemia. However, GFAP-immunoreactive astrocytes were apparently damaged two days after both ischemiae. At five days after ischemiae, astrocyte endfeet around capillary endothelial cells were severely ruptured. They were more severely ruptured by severe ischemia than by mild ischemia. However, the number of astrocytes stained with S100 was significantly higher in severe ischemia than in mild ischemia. These results indicate that the degree of astrogliosis, including the disruption (loss) of astrocyte endfeet following ischemia and reperfusion in the forebrain, might depend on the severity of ischemia and that the degree of ischemia-induced neuronal damage may be associated with the degree of astrogliosis.

Neuroplasticity in Motor Learning Under Variable and Constant Practice Conditions-Protocol of Randomized Controlled Trial.

BackgroundThere is numerous literature on mechanisms underlying variability of practice advantages. Literature includes both behavioral and neuroimaging studies. Unfortunately, no studies are focusing on practice in constant conditions to the best of our knowledge. Hence it is essential to assess possible differences in mechanisms of neuroplasticity between constant vs. variable practice conditions. The primary objectives of the study described in this protocol will be: (1) to determine the brain’s structural and functional changes following constant and variable practice conditions in motor learning (structural and functional magnetic resonance imaging, MRI); (2) to determine the EEG activation and connectivity between cognitive, sensory, and motor cerebral cortex areas (central, temporal, parietal, occipital) in constant and variable practice conditions and as a function of practice time.MethodsThe study will follow the interventional (experimental) design with two arms (parallel groups). Fifty participants will be randomly assigned to two groups practicing in constant (CG) and variable conditions (VG). CG will be practicing only one pattern of step isometric contractions during unimanual index finger abduction, i.e., 90 trials in all training sessions, whereas VG will practice three different patterns. Each will be practiced 30 times per session in variable conditions. Resting-state fMRI, EEG (cortical networking), and motor task proficiency will be examined before (pre-) and after practice (post- and retentions tests).DiscussionFindings will enhance our understanding of structural and functional neural changes following practice in constant and variable conditions. Therefore, the study can be considered pure (basic) research (clinical research in healthy individuals).Clinical Trial RegistrationStudy registered at clinicaltrials.gov (ID# NCT04921072) on 9 June 2021. Last version update: 21 December 2021.The protocol has been prepared according to the complete SPIRIT checklist (http://www.spirit-statement.org/), although the item order has been modified in order to comply with the manuscript structure.

Shaping the Sensory-Motor Network by Short-Term Unresolvable Sensory-Motor Mismatch.

Learning from errors as the main mechanism for motor adaptation has two fundamental prerequisites: a mismatch between the intended and performed movement and the ability to adapt motor actions. Many neurological patients are limited in their ability to transfer an altered motor representation into motor action due to a compromised motor pathway. Studies that have investigated the effects of a sustained and unresolvable mismatch over multiple days found changes in brain processing that seem to optimize the potential for motor learning (increased drive for motor adaptation and a weakening of the current implementation of motor programs). However, it remains unclear whether the observed effects can be induced experimentally and more important after shorter periods. Here, we used task-based and resting-state fMRI to investigate whether the known pattern of cortical adaptations due to a sustained mismatch can be induced experimentally by a short (20 min), but unresolvable, sensory–motor mismatch by impaired facial movements in healthy participants by transient facial tapping. Similar to long-term mismatch, we found plastic changes in a network that includes the striatal, cerebellar and somatosensory brain areas. However, in contrast to long-term mismatch, we did not find the involvement of the cerebral motor cortex. The lack of the involvement of the motor cortex can be interpreted both as an effect of time and also as an effect of the lack of a reduction in the motor error. The similar effects of long-term and short-term mismatch on other parts of the sensory–motor network suggest that the brain-state caused by long-term mismatch can be (at least partly) induced by short-term mismatch. Further studies should investigate whether short-term mismatch interventions can be used as therapeutic strategy to induce an altered brain-state that increase the potential for motor learning.

Effect of Sensory Integration, Neurodevelopmental Therapy and Behavioral Therapy on Overall Development in a Child with Cerebral Palsy: An Interesting Case Report

Cerebral palsy (CP) is a collection of conditions that impact a person's ability to move, balance, and maintain posture. Cerebral palsy is a disorder that affects the motor portion of the brain's outer layer, which controls muscular movement. The cerebral motor cortex hasn't formed normally in some situations throughout fetal development. In certain cases, the impairment is caused by a brain injury that occurred before, during, or after delivery. In either situation, the damage is irreversible, and the resulting disabilities are permanent. The nature and intensity of CP symptoms vary from one person to the next, and they can even alter over time. Depending on whether areas of the brain have been affected, symptoms might vary widely from person to person. Cerebral palsy affects mobility and posture in all persons, and some people may have intellectual disabilities, seizures, odd bodily feelings or perceptions, and other medical issues. People with CP may also have vision or hearing impairments, as well as language and speaking issues. The present case report is of a child of 2.5 years old. She came with complaints of difficulty in sit to stand, standing with maximum assistance, very minimal standing balance, requires total assistance in walking. She was also having some sensory and behavioral issues reported by parents like trying to catch her own shadow, blabbering among herself. She was assessed, treatment including Sensory integration and Neurodevelopmental therapy was given to her for a period of 6 months. Baby improved profoundly well.

Chapter 6 - Critical roles for breathing in the genesis and modulation of emotional states

Breathing can be classified into metabolic and behavioral categories. Metabolic breathing and voluntary behavioral breathing are controlled in the brainstem and in the cerebral motor cortex, respectively. This chapter places special emphasis on the reciprocal influences between breathing and emotional processes. As is the case with neural control of breathing, emotions are generated by multiple control networks, located primarily in the forebrain. For several decades, a respiratory rhythm generator has been investigated in the limbic system. The amygdala receives respiratory-related input from the piriform cortex. Excitatory recurrent branches are located in the piriform cortex and have tight reciprocal synaptic connections, which produce periodic oscillations, similar to those recorded in the hippocampus during slow-wave sleep. The relationship between olfactory breathing rhythm and emotion is seen as the gateway to interpreting the relationship between breathing and emotion. In this chapter, we describe roles of breathing in the genesis of emotion, neural structures common to breathing and emotion, and mutual importance of breathing and emotion. We also describe the central roles of conscious awareness and voluntary control of breathing, as effective methods for stabilizing attention and the contents in the stream of consciousness. Voluntary control of breathing is seen as an essential practice for achieving emotional well-being.

Effect of electroacupuncture combined with motor training on motor learning and motor cortex excitability

To compare the effect of electroacupuncture (EA), motor training (MT) and EA combined with MT on motor learning and motor cortex excitability in healthy subjects, and to explore the effect of EA combined with MT on synaptic metaplasticity. Using self-control design, 12 healthy subjects were assigned into an EA group, a motor training group (MT group) and an EA plus motor training group (EA+MT group) successively, wash-out period of at least 2 weeks was required between each group. EA was applied at left Hegu (LI 4) in the EA group for 30 min, with continuous wave, 2 Hz in frequency and 0.5-1 mA in density. Motor training of left hand was adopted in the MT group for 30 min. EA and motor training were adopted in the EA+MT group successively. The time of finishing grooved pegboard test (GPT) was observed, and the average amplitude of motor evoked potentials (MEPs), the rest motor threshold (rMT) and the latency were recorded by transcranial magnetic stimulation technique before intervention (T0), after intervention (T1) and 30 min after EA (T3) in the EA group and the EA+MT group, T0 and T1 in the MT group. Compared with T0, the time of finishing GPT was shortened at T1 in the MT group and at T2 in the EA group and the EA+MT group (P<0.01, P<0.05), the average amplitude of MEPs was increased at T1 in the 3 groups and at T2 in the EA group and the EA+MT group (P<0.05, P<0.01). Compared with T1, the time of finishing GPT at T2 was shortened in the EA group and the EA+MT group (P<0.05, P<0.01), the average amplitude of MEPs at T2 was increased in the EA group (P<0.05). The time of finishing GPT at T2 in the EA+MT group was shorter than the EA group (P<0.05). There were no statistical differences in rMT and latency at each time point among the 3 groups (P>0.05). In physiological state, electroacupuncture combined with motor training have a synergistic effect on motor learning, while have no such effect on excitability of cerebral motor cortex.