Basic and Clinical Neuroscience
Volume:14 Issue: 1, Jan -Feb 2023

A patient with epilepsy was shown to have neurobiological, psychological, cognitive, and social issues as a result of recurring seizures, which is regarded as a chronic brain disease. However, despite numerous drug treatments, approximately, 30%-40% of all patients are resistant to antiepileptic drugs. Therefore, newer therapeutic modalities are introduced into clinical practice which involve neurostimulation and direct stimulation of the brain. Hence, we review published literature on vagus nerve stimulation, trigeminal nerve stimulation, applying responsive stimulation systems, and deep brain stimulation (DBS) in animals and epileptic patient with an emphasis on drug-resistant epilepsy.

Electroconvulsive therapy (ECT) is an effective treatment for some psychiatric disorders. It is postulated that ECT should primarily be considered for patients with treatment-resistant obsessive-compulsive disorder (OCD) in the context of major depression. Therefore, we aimed to evaluate the efficacy of ECT in OCD patients without comorbid psychiatric disorders.

This quasi-experimental study was conducted on 12 adult patients with severe OCD (Yale-Brown test score above 25) and no comorbid psychiatric disorders referred to a tertiary care hospital for psychiatric disorders. Treatment was administered three times a week for up to three to four weeks (a minimum of 8 sessions and a maximum of 12 sessions). We completed the Yale-Brown test for all patients before ECT, on the day after applying ECT, and two months after the final ECT session to evaluate the effect of therapy.

Yale-Brown patients’ Mean±SD significantly decreased after the ECT sessions from 28.08±2.50 to 17.17±3.78 (P=0.043). After treatment, the severity of OCD decreased in all patients and turned to mild and moderate levels in 4 patients (33.3%) and 8 (66.7%), respectively. After two months, the Mean±SD Yale-Brown score slightly increased to 18.08±1.62 (P=0.125), and the severity of OCD in all 12 patients (100%) became moderate. Nevertheless, in none of them, the Yale-Brown score increased and returned to the baseline value in this period. None of the patients developed significant side effects during or after ECT sessions.

ECT was a safe and effective therapeutic strategy for patients with treatment-resistant OCD with no comorbid psychiatric disorders. However, further randomized controlled trials are required to validate the efficacy of ECT for OCD treatment before implementing it in the routine clinical practice.

Strategies of Schwann cell (SC) transplantation for regeneration of peripheral nerve injury involve many limitations. Stem cells can be used as alternative cell source for differentiation into Schwann cells. Given the high potential of neural crest-derived stem cells for the generation of multiple cell lineages, in this research, we considered whether olfactory ectomesenchymal stem cells (OE-MSCs) derived from neural crest can spontaneously differentiate into SC lineage

OE-MSCs were isolated from human nasal mucosa and characterized by the mesenchymal and neural crest markers. The cells were cultured in glial growth factors-free medium and further investigated in terms of the phenotypic and functional properties. 

Immunocytochemical staining and real-time PCR analysis indicated that the cultured OE-MSCs expressed SCs markers, SOX10, p75, S100, GFAP and MBP, differentiation indicative. It was found that the cells could secrete neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Furthermore, after co-cultured with PC12, the mean neurite length was enhanced by OE-MSCs. 

The findings indicated that OE-MSCs could be differentiated spontaneously into SC-like phenotypes, suggesting their applications for transplantation in peripheral nerve injuries.

This study aimed at investigating the stimulation by intra-spinal signals decoded from electrocorticography (ECoG) assessments to restore the movements of the leg in an animal model of spinal cord injury (SCI).

The present work is comprised of three steps. First, ECoG signals and the associated leg joint changes (hip, knee, and ankle) in sedated healthy rabbits were recorded in different trials. Second, an appropriate set of intra-spinal electric stimuli was discovered to restore natural leg movements, using the three leg joint movements under a fuzzy-controlled strategy in spinally-injured rabbits under anesthesia. Third, a nonlinear autoregressive exogenous (NARX) neural network model was developed to produce appropriate intra-spinal stimulation developed from decoded ECoG information. The model was able to correlate the ECoG signal data to the intra-spinal stimulation data and finally, induced desired leg movements. In this study, leg movements were also developed from offline ECoG signals (deciphered from rabbits that were not injured) as well as online ECoG data (extracted from the same rabbit after SCI induction).

Based on our data, the correlation coefficient was 0.74±0.15 and the normalized root means square error of the brain-spine interface was 0.22±0.10.

Overall, we found that using NARX, appropriate information from ECoG recordings can be extracted and used for the generation of proper intra-spinal electric stimulations for restoration of natural leg movements lost due to SCI.

Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis. 

The aim of this study was to investigate the Reelin signalling pathway in the MTLE patients. Therefore, we studied each step in the Reelin signalling pathway for the gene and protein expressions, in the hippocampal tissue obtained from patients undergoing surgery for MTLE and compared it with age matched normal autopsy cases. 

We found statistically significant decrease (P<0.001) in the Reelin mRNA expression in MTLE patients. Among the two reelin receptors, apolipoprotein E receptor 2 (ApoER2) was significantly increased whereas very low density lipoprotein receptor (VLDLR) was decreased among the patients. Disabled 1 (Dab1), the downstream target of reelin, was found to be decreased. Dab1 in turn inhibits Cofilin, which is responsible for cytoskeletal reorganization, thus limiting aberrant neuronal migration. Statistically significant over expression of Cofilin protein was found in the patient group. Matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteases-1 (TIMP-1), both of which are involved in processing of Reelin, were down regulated in 70-85% of cases. 

The whole pathway was found to be deranged in MTLE. These results indicate that Reelin signalling pathway is disturbed at various points in the MTLE patients and might be involved in the pathogenesis & progression of MTLE. Our results extend the existing information regarding the components of the Reelin pathway and further, establish a link between pathway disturbance and MTLE.

Extensive human and animal research shows that exercise has beneficial effects on multiple clinical outcomes for patients suffering from multiple sclerosis (MS). This research was conducted to examine the effect of aerobic exercise with probiotic consumption on the myelination of nerve fibers in a cuprizone-induced demyelination mouse model of MS. 

Rats exposed to cuprizone (CPZ) for 13 weeks were subjected to motor and balance tests in week 5. They (5 people in each group) were assigned to five groups of control (C), MS, MS with exercise (MS+Exe), MS with probiotic (MS+Pro), and MS with probiotic and exercise (MS+Pro+Exe) randomly. The exercise groups conducted aerobic exercises 5 days a week for 60 days. The rats received probiotics by gavage. Performance and balance tests were repeated when the eight-week protocol of exercise and probiotic consumption was finished. One day after these interventions, they were sacrificed to undergo biochemical and molecular biology assays.

The results showed that Myelin basic protein (MBP) was increased in the MS+Pro+Exe, MS+Pro, and MS+Exe compared to the MS group (P<0.05). 
The nestin mRNA showed an increase in MS+Pro+Exe, MS+Exe, and MS+Pro groups compared to the MS group, but this increase was not significant in MS+Pro+Exe and MS+Exe groups compared to the control and MS groups (P>0.05). 

According to the results, lifestyle interventions can effectively alleviate demyelinating-inflammatory processes that happen in the brains of MS patients.

Nowadays, deep learning and convolutional neural networks (CNNs) have become widespread tools in many biomedical engineering studies. CNN is an end-to-end tool, which makes the processing procedure integrated, but in some situations, this processing tool requires to be fused with machine learning methods to be more accurate.

In this paper, a hybrid approach based on deep features extracted from wavelet CNNs (WCNNs) weighted layers and multiclass support vector machine (MSVM) was proposed to improve the recognition of emotional states from electroencephalogram (EEG) signals. First, EEG signals were preprocessed and converted to Time-Frequency (T-F) color representation or scalogram using the continuous wavelet transform (CWT) method. Then, scalograms were fed into four popular pre-trained CNNs, AlexNet, ResNet-18, VGG-19, and Inception-v3 to fine-tune them. Then, the best feature layer from each one was used as input to the MSVM method to classify four quarters of the valence-arousal model. Finally, the subject-independent leave-one-subject-out criterion was used to evaluate the proposed method on DEAP and MAHNOB-HCI databases.

Results showed that extracting deep features from the earlier convolutional layer of ResNet-18 (Res2a) and classifying using the MSVM increased the average accuracy, precision, and recall by about 20% and 12% for MAHNOB-HCI and DEAP databases, respectively. Also, combining scalograms from four regions of pre-frontal, frontal, parietal, and parietal-occipital and two regions of frontal and parietal achieved the higher average accuracy of 77.47% and 87.45% for MAHNOB-HCI and DEAP databases, respectively.

Combining CNN and MSVM increased the recognition of emotion from EEG signals and the results were comparable to state-of-the art studies.

We previously reported that datumetine possesses binding affinity with N-methyl-D-aspartate receptor (NMDAR) and that 14-day exposure to datumetine altered NMDAR signaling by mimicking glutamate toxicity. Here, we investigated the potential neuroprotective effect of a single shot of a low dose of datumetine administration in BALB/c mice.

30 male adult BALB/c mice were used for the study. The mice were randomly divided into three groups of ten mice each with an intraperitoneal injection of 0.1 mL of 10% DMSO for the Vehicle group, Datumetine group were administered 0.1 mg/kg body weight (bw) of datumetine and MK-801+Datumetine group were administered 0.5 mg/kg bw of MK-801 (to block NMDAR) followed by 0.1 mg/kg bw of datumetine after 30 minutes. 24 hours after administration, mice were euthanized in an isoflurane chamber followed by perfusion with 1X PBS. Brains were excised and stored at -200C till further processing. Mice designated for IHC were further perfused with 4% PFA and brain excised and stored in 4% PFA till further processing. NMDAR signalling molecules expression was evaluated in frozen brain samples and the fixed brain samples were stained for neuron, vGlut and NMDAR subtypes.

Relative to vehicle (Veh), datumetine downregulate calcium calmodulin kinase II alpha (CamKIIα) expression in the hippocampus and prefrontal cortex (PFC) but not in the cerebellum, cyclic AMP response element binding protein (CREB) was also upregulated only in the PFC but phosphorylated CREB (pCREB) was also upregulated in three brain regions observed, while brain-derived neurotrophic factor (BDNF) was only upregulated in hippocampus and PFC of Datumetine relative to vehicle (Veh). On the other hand, dizocilpine (MK-801) reversed some of the effects of datumetine in the observed brain regions. No major histological alterations were observed in the different brain regions immunohistochemically.

We conclude that a low dose of datumetine moderately enhances NMDAR activity. This showed the neuroprotective potentials of low datumetine exposure.

Numerous studies have shown the positive effects of rosmarinic acid on the nervous system.Rosmarinic acid as a herbal compound with anti-inflammatory effects can prevent thedestructive effect of inflammation on the nervous system. Furthermore, various studies haveemphasized the advantages of three-dimensional (3D) culture over the two-dimensional (2D) culture of cells. 

In this study, thermosensitive chitosan (CH)-based hydrogel as a 3D scaffoldwith the combination of chitosan, beta-glycerol phosphate and hydroxyl ethyl cellulose (CH-GP-HEC) loaded with rosmarinic acid was used to induce neuronal differentiation in humanWharton jelly stem cells. Also, cells were divided into eight groups to evaluate the effect of 3Dcell culture and to compare gene expression in different induction conditions.

The results ofgene expression analysis showed the highest expression of neuronal markers in Whartons jelly derived mesenchymal stem cells (WJMSCs) cultured in chitosan, beta-glycerol phosphate and hydroxyl ethyl cellulose (ch-gp-hec) loaded with differentiation medium androsmarinic acid. According to the results of gene expression, rosmarinic acid alone has a positiveeffect on the induction of expression of neural markers. This positive effect is enhanced by cellculture in 3D conditions. 

This study shows that rosmarinic acid can be considered an inexpensiveand available compound for use in neural tissue engineering. The results of this study indicatethat rosmarinic acid can be considered a cheap and available compound for use in neural tissueengineering.

Previous studies have reported dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) activation during the performance of spatial working memory (SWM), therefore this study aims to compare the effect of transcranial direct current stimulation (tDCS) between these two areas. 

Fifty-four healthy right-handed students (27 women, 27 men; age=24.3±0.2 years) were randomly assigned to an anodal group (n=27) and a sham group (n=27), each of these groups was divided into F4 (representing right DLPFC) or P4 (representing right PPC) subgroups, respectively. A computerized Corsi block tapping (CBT) task was used to measure SWM. The tDCS intervention consisted of five daily sessions with a direct current of 1.5 mA for 15 minutes on the F4 or P4 area of the brain at 24-hour intervals. 

Significant enhancement of the SWM span as well as a faster response was observed after anodal tDCS in both the anterior and posterior direction. Moreover, stimulation of the left DLPFC induced a faster reaction time compared to the right PPC.

Stimulation DLPFC and PPC, as an element of the frontoparietal network, showed SWM enhancement, with the DLPFC being more affected. Our finding provides new evidence to compare the effect of stimulation on the two main activated cortical areas during visual SWM.

This study aimed to compare the diagnostic value of four questionnaires for the diagnosis of neurocognitive disorders (NCDs) in the elderly.

 In this project, people older than 60 years who lived in Tehran were investigated. A total of 99 literate cases were enrolled in the study, and four questionnaires, including functional assessment staging tool (FAST), abbreviated mental test score (AMTS), mini-mental state examination (MMSE), and modified Persian test of elderly for assessment of cognition and executive function (PEACE) were completed for them. They were then referred to a neuropsychiatrist, and the status of their cognition and neurobehavior was determined. The specialists were blinded to the results of the tests.

Of the 99 participants studied, 39 cases were healthy, eight cases had mild Alzheimer’s disease, 38 had amnesic MCI, five cases had secondary dementia, and nine cases had mixed vascular dementia and Alzheimer’s disease. The area under the ROC curve for distinguishing the healthy group from the rest of the population was 0.692, 0.629, 0.734, and 0.751 for the FAST, AMTS, MMSE, and NBCSS questionnaires, respectively.

MMSE and NBCSS tests had better diagnostic power than the other two tests to distinguish the healthy group from the rest of the population.

This study aimed to investigate the influence of neglect and the effect of prism adaptation (PA) combined with continuous Theta-burst transcranial magnetic stimulation (cTBS) on the art constructive errors in painting rehabilitation of stroke patients with neglect.

Fourteen patients with neglect and art constructive errors in painting secondary to stroke were randomly assigned to the rehabilitation group and received PA combined with the inhibitory protocol of cTBS over the intact parietal cortex; the control group received PA combined with sham cTBS for two weeks in ten daily sessions. Patients were assessed for art constructive errors in painting in figure copying test (FCT), and coloring test (CT) before and after the intervention. Art constructive errors in painting were classified into omission, deformation, size, neglect of warm colors, and perseveration of errors. Neglect was evaluated using the line bisection task (LBT), figure copying test (FCT), and coloring test (CT).

All patients showed a significant improvement in art constructive errors in painting (measured using the pattern of painting’ errors in FCT and CT), and neglect (measured using LBT, FCT, and CT) (p<0.05). Omission, neglect of warm colors, and deformation were the most frequent errors.

Neglect and rehabilitation influence the painting system in stroke patients. Both approaches improved art constructive errors in painting and neglect symptoms.

Cognitive deficit is one of the common comorbidity accompanying epilepsy. The present study evaluated the effect of Celastrus paniculatus seed extract on seizure severity and cognitive deficit following the pentylenetetrazole (PTZ)-induced chemical kindling model.

PTZ kindling model was developed by daily administration of the sub-convulsive dose of PTZ 30 mg/kg for four weeks. After four weeks of induction, the following treatment, namely sodium valproic acid (SVA) 200 mg/kg, C. paniculatus 500 mgkg, pergolide 2 mg/kg, C. paniculatus (250 mgkg)+ Pergolide (1 mg/kg), and C. paniculatus (250 mgkg)+ SVA (100 mg/kg) were administered 30 minutes prior to PTZ (30 mg/kg) injection for a period of next 14 days. Neurobehavioral parameters, including superoxide dismutase (SOD), Catalase (CAT), glutathione (GSH), and dopamine levels were assessed and the Morris water maze test (MWM) and Grip strength test (GPS) were performed. Hematoxylin & Eosin (H&E) staining of hippocampal cornu ammonis (CA1), CA2, CA3, dentate gyrus (DG), and frontal cortex was performed.

C. paniculatus (500 mg/kg) alone and in combination ( C. paniculatus (250 mgkg)+ pergolide (1 mg/kg) and C. paniculatus (250 mgkg)+ SVA (100 mg/kg)) significantly (p<0.05) reduced the seizure score, mean latency time, and distance traveled in the MWM. However, no significant effect was seen in GPS. Biochemical analysis showed elevated antioxidant markers, namely GSH, CAT, and SOD, and also elevated dopamine levels. C. paniculatus and its combination also significantly (P<0.05) protected against neuronal loss in the hippocampus and frontal cortex evidenced by H&E staining

C. paniculatus alone and in combination with other agents may have the potential to treat epilepsy and associated cognitive deficits

Numerous studies in humans and animals hypothesize that gut microbiota dysbiosis is involved in the development of behavioral and neurological diseases such as depression, autism spectrum disorder, Parkinson disease, multiple sclerosis, stroke and Alzheimer's disease. Some of the most salient works so far regarding the brain-gut axis are mentioned below. The current knowledge on the impact of gut microbiota on nervous system diseases is far from being directly used for pharmacologic or nutritional advice toward restoration of normal bodily functions. It seems that a more comprehensive approach should be followed so that the individual effect of each kind of intervention on the patient’s somatic or psychological status is determined. Future research must address global need for regimens which could re-establish normal composition of gut microorganisms after each neuropsychological disorder.