Neuronal Reorganization Research Articles

Vitamin D Mitigates Depression-related Disorders in an Animal Model of Depression: A Behavioral, Anatomopahtological, and Molecular Investigation, Implicating the Hippocampal BDNF Signaling Pathway

Background: Major depressive disorder represents a complicated mental disorder characterized by persistent feelings of unhappiness and loss of interest. More evidence suggests a high potential correlation between vitamin D deficiency and depression. However, the underlying mechanisms and the therapeutic potential of vitamin D supplementation are still not properly understood. The purpose of this research is to evaluate the effect of vitamin D supplementation on depressive behaviors using a rat model of depression and explore the potential mechanisms involved. Depression is a prevalent mental health disorder that significantly impacts the quality of life of individuals. Despite the availability of various treatment options, many patients still experience suboptimal outcomes, highlighting the need for further exploration of novel therapeutic approaches. In recent years, the importance of vitamin D in mental health, particularly in depression, has gained considerable attention. Methods: In this project, we propose to utilize an animal model of depressed rats to evaluate the effect of vitamin D supplementation on depressive behaviors. We employed a range of well-established behavioral tests to assess changes in depressive-like behaviors following vitamin D supplementation. Additionally, histopathological examinations of the hippocampal region, known to be involved in mood regulation, were performed to assess structural alterations and cellular changes associated with depression and vitamin D supplementation. Results: The findings demonstrate the therapeutic potential of vitamin D supplementation by improving neuronal reorganization and proliferation in the hippocampus, suggesting an interest in investigating other mechanisms of interaction. Conclusion: The findings of this research will provide valuable insight into the therapeutic potential of vitamin D in depression and shed light on the underlying mechanisms involved.

Local neuronal sleep after stroke: The role of cortical bistability in brain reorganization

BackgroundAcute cerebral ischemia triggers a number of cellular mechanisms not only leading to excitotoxic cell death but also to enhanced neuroplasticity, facilitating neuronal reorganization and functional recovery. ObjectiveTransferring these cellular mechanisms to neurophysiological correlates adaptable to patients is crucial to promote recovery post-stroke. The combination of TMS and EEG constitutes a promising readout of neuronal network activity in stroke patients. MethodsWe used the combination of TMS and EEG to investigate the development of local signal processing and global network alterations in 40 stroke patients with motor deficits alongside neural reorganization from the acute to the chronic phase. ResultsWe show that the TMS-EEG response reflects information about reorganization and signal alterations associated with persistent motor deficits throughout the entire post-stroke period. In the early post-stroke phase and in a subgroup of patients with severe motor deficits, TMS applied to the lesioned motor cortex evoked a sleep-like slow wave response associated with a cortical off-period, a manifestation of cortical bistability, as well as a rapid disruption of the TMS-induced formation of causal network effects. Mechanistically, these phenomena were linked to lesions affecting ascending activating brainstem fibers. Of note, slow waves invariably vanished in the chronic phase, but were highly indicative of a poor functional outcome. ConclusionIn summary, we found evidence that transient effects of sleep-like slow waves and cortical bistability within ipsilesional M1 resulting in excessive inhibition may interfere with functional reorganization, leading to a less favorable functional outcome post-stroke, pointing to a new therapeutic target to improve recovery of function.

Differential Regulation of Wnt/β-catenin Signaling in Acute and Chronic Epilepsy in Repeated Low Dose Lithium-Pilocarpine Rat Model of Status Epilepticus

Epilepsy is a chronic neurological complication characterized by unprovoked seizure episodes due to the imbalance between excitatory and inhibitory neurons. The epileptogenesis process has been reported to be involved in chronic epilepsy however, the mechanism underlying epileptogenesis remains unclear. Recent studies have shown the possible involvement of Wnt/β-catenin signaling in the neurogenesis and neuronal reorganization in epileptogenesis. In this study, we used repeated low dose lithium-pilocarpine model of status epilepsy (SE) to study the involvement of Wnt/β-catenin signaling at acute and chronic stages post SE induction. The acute study ranged from day 0 to day 28 post SE induction and the chronic study ranged from day 0 to day 56 post SE induction. Several neurobehavioral parameters and seizure score and seizure frequency was analysed until the end of the study. The proteins involved in the regulation of Wnt/β-catenin signaling and downstream cascading were analysed using western blot and quantitative real-time PCR analysis. The Wnt/β-catenin pathway was found inactive in acute SE, while the same was found activated at the chronic stage. Our findings suggest that the activated Wnt/β-catenin signaling in chronic epilepsy might be the possible mechanism underlying epileptogenesis as indicated by increased neuronal count, increased synaptic density, astrogliosis and apoptosis in chronic epilepsy. These findings can help target the Wnt/β-catenin pathway differentially depending upon the type of epilepsy. The acute stage characterized by SE can be improved by targeting GSK-3β levels and the chronic stage characterized by temporal lobe epilepsy can be improved by targeting β-catenin and disheveled proteins.

Exploration of Molecular Targets and Mechanisms of Curcumin in the Treatment of COVID-19 with Depression by an Integrative Pharmacology Strategy.

Coronavirus disease 2019 (COVID-19) not only causes a range of respiratory symptoms but also has a great impact on individual mental health. With the global pandemic of SARS-CoV-2, the incidence of COVID-19 comorbid with depression has increased significantly. Curcumin, a natural polyphenol compound, has been shown to have antidepressant and anti-coronavirus activities. This study aimed to explore the molecular targets and underlying biological mechanisms of curcumin in the treatment of COVID-19 with depression through an integrative pharmacology strategy, including target prediction, network analysis, PPI analysis, GO and KEGG enrichment analyses, and molecular docking. After a comprehensive search and thorough analysis, 8 core targets (ALB, AKT1, CASP3, STAT3, EGFR, PTGS2, FOS, and SERPINE1) were identified. GO and KEGG enrichment analysis results revealed that the pathways related to viral infection, immune regulation, neuronal reorganization, apoptosis, and secretion of inflammatory cytokines were involved in the pathological process. Furthermore, molecular docking showed that curcumin could spontaneously bind to the SARS-CoV-2-related receptor proteins and the core targets with a strong binding force. The potential pharmacological mechanisms of curcumin in COVID-19 comorbid depression were evaluated. Curcumin can be used as a therapeutic agent for COVID-19 comorbid depression. One of the potential mechanisms may be to reduce the inflammatory response and suppress the cytokine storm by regulating the JAK-STAT signaling pathway and MAPK signaling pathway. These findings may help to overcome the impact of the COVID-19 pandemic on psychological health.

A novel organotypic cortical slice culture model for traumatic brain injury: molecular changes induced by injury and mesenchymal stromal cell secretome treatment.

Traumatic brain injury (TBI) is a major worldwide neurological disorder with no neuroprotective treatment available. Three-dimensional (3D) in vitro models of brain contusion serving as a screening platform for drug testing are lacking. Here we developed a new in vitro model of brain contusion on organotypic cortical brain slices and tested its responsiveness to mesenchymal stromal cell (MSC) derived secretome. A focal TBI was induced on organotypic slices by an electromagnetic impactor. Compared to control condition, a temporal increase in cell death was observed after TBI by propidium iodide incorporation and lactate dehydrogenase release assays up to 48 h post-injury. TBI induced gross neuronal loss in the lesion core, with disruption of neuronal arborizations measured by microtubule-associated protein-2 (MAP-2) immunostaining and associated with MAP-2 gene down-regulation. Neuronal damage was confirmed by increased levels of neurofilament light chain (NfL), microtubule associated protein (Tau) and ubiquitin C-terminal hydrolase L1 (UCH-L1) released into the culture medium 48 h after TBI. We detected glial activation with microglia cells acquiring an amoeboid shape with less ramified morphology in the contusion core. MSC-secretome treatment, delivered 1 h post-injury, reduced cell death in the contusion core, decreased NfL release in the culture media, promoted neuronal reorganization and improved microglia survival/activation. Our 3D in vitro model of brain contusion recapitulates key features of TBI pathology. We showed protective effects of MSC-secretome, suggesting the model stands as a tractable medium/high throughput, ethically viable, and pathomimetic biological asset for testing new cell-based therapies.

Learning-induced reorganization of number neurons and emergence of numerical representations in a biologically inspired neural network

Number sense, the ability to decipher quantity, forms the foundation for mathematical cognition. How number sense emerges with learning is, however, not known. Here we use a biologically-inspired neural architecture comprising cortical layers V1, V2, V3, and intraparietal sulcus (IPS) to investigate how neural representations change with numerosity training. Learning dramatically reorganized neuronal tuning properties at both the single unit and population levels, resulting in the emergence of sharply-tuned representations of numerosity in the IPS layer. Ablation analysis revealed that spontaneous number neurons observed prior to learning were not critical to formation of number representations post-learning. Crucially, multidimensional scaling of population responses revealed the emergence of absolute and relative magnitude representations of quantity, including mid-point anchoring. These learnt representations may underlie changes from logarithmic to cyclic and linear mental number lines that are characteristic of number sense development in humans. Our findings elucidate mechanisms by which learning builds novel representations supporting number sense.

Actin reorganization in hippocampal neurons may play a role in early learning and memory impairment after propofol anesthesia in rats

Objectives To observe changes in actin and dendritic spines in the hippocampus after propofol anesthesia, and to evaluate the role of these changes in subsequent learning impairment in both young (3-month-old) and aged (20-month-old) male rats. Methods The shuttle box test was used to evaluate learning from 1, 3, 7, or 14 days after anesthesia. Both F-actin content and dendritic spines in the hippocampal CA1 region were observed using immunofluorescent staining and western blot assays. Results The latency of the escape response was significantly prolonged until 7 days after anesthesia in the aged rats, and their learning curves were shifted. Dendritic spines were also decreased in the aged rats within 7 days after anesthesia, and F-actin content was significantly increased until 14 days after anesthesia. Conclusions Learning was inhibited after propofol anesthesia, especially in aged rats. The over-polymerization of actin and subsequent reorganization of dendritic spines in the hippocampus may be responsible for this learning impairment. Our findings suggest that synaptic plasticity may be an underlying mechanism of perioperative neurocognitive disorders.

Post-stroke hand synergy formation variant. Clinical case

Pathological synergies are a frequent consequence of cerebrovascular accidents and hinders further recovery. The existing concept of the formation of pathological synergies considers them as a compensatory strategy in response to damage to the pyramidal tract, which, due to paresis and increased muscle tone, has acquired a pathological character. Recent studies in primates have shown that the contralateral hemisphere, in particular the reticulospinal and rubrospinal tracts, may be involved in motor control of the hand. The current hypothesis presents the corticoreticulospinal and corticorubrospinal tracts as a back-up system for neuronal reorganization due to injury.
 This clinical case describes the role of the white matter of the contralateral hemisphere in the mechanism of formation of pathological flexion synergy, based on data from the analysis of movements and neuroimaging.

Reproducible Microstructural Changes in the Brain Associated With the Presence and Severity of Urologic Chronic Pelvic Pain Syndrome (UCPPS): A 3-Year Longitudinal Diffusion Tensor Imaging Study From the MAPP Network

Microstructural alterations have been reported in patients with urologic chronic pelvic pain syndrome (UCPPS). However, it isn't clear whether these alterations are reproducible within 6 months or whether long-term symptom improvement is associated with specific microstructural changes. Using data from the MAPP-II Research Network, the current study performed population-based voxel-wise DTI and probabilistic tractography in a large sample of participants from the multicenter cohort with UCPPS (N = 364) and healthy controls (HCs, N = 61) over 36 months. While fractional anisotropy (FA) differences between UCPPS patients and HCs were observed to be unique at baseline and 6-month follow-up visits, consistent aberrations in mean diffusivity (MD) were observed between UCPPS and HCs at baseline and repeated at 6 months. Additionally, compared to HCs, UCPPS patients showed stronger structural connectivity (SC) between the left postcentral gyrus and the left precuneus, and weaker SC from the left cuneus to the left lateral occipital cortex and the isthmus of the left cingulate cortex at baseline and 6-month. By 36 months, reduced FA and MD aberrations in these same regions were associated with symptom improvement in UCPPS. Together, results suggest changes in white matter microstructure may play a role in the persistent pain symptoms in UCPPS. PerspectiveThis longitudinal study identified reproducible, “disease-associated” patterns in altered mean diffusivity and abnormal microstructural connectivity in UCPPS comparing to HCs over 6 months. These differences were found in regions involved in sensory processing and integration and pain modulation, making it potentially amenable for clinical interventions that target synaptic and/or neuronal reorganization.

Technical feasibility of using auditory phase-targeted stimulation after pediatric severe traumatic brain injury in an intensive care setting

BackgroundSupplementary treatment options after pediatric severe traumatic brain injury (TBI) are needed to improve neurodevelopmental outcome. Evidence suggests enhancement of brain delta waves via auditory phase-targeted stimulation might support neuronal reorganization, however, this method has never been applied in analgosedated patients on the pediatric intensive care unit (PICU). Therefore, we conducted a feasibility study to investigate this approach: In a first recording phase, we examined feasibility of recording over time and in a second stimulation phase, we applied stimulation to address tolerability and efficacy.MethodsPediatric patients (> 12 months of age) with severe TBI were included between May 2019 and August 2021. An electroencephalography (EEG) device capable of automatic delta wave detection and sound delivery through headphones was used to record brain activity and for stimulation (MHSL-SleepBand version 2). Stimulation tolerability was evaluated based on report of nurses, visual inspection of EEG data and clinical signals (heart rate, intracranial pressure), and whether escalation of therapy to reduce intracranial pressure was needed. Stimulation efficacy was investigated by comparing EEG power spectra of active stimulation versus muted stimulation (unpaired t-tests).ResultsIn total, 4 out of 32 TBI patients admitted to the PICU (12.5%) between 4 and 15 years of age were enrolled in the study. All patients were enrolled in the recording phase and the last one also to the stimulation phase. Recordings started within 5 days after insult and lasted for 1–4 days. Overall, 23–88 h of EEG data per patient were collected. In patient 4, stimulation was enabled for 50 min: No signs of patient stress reactions were observed. Power spectrums between active and muted stimulation were not statistically different (all P > .05).ConclusionResults suggests good feasibility of continuously applying devices needed for auditory stimulation over multiple days in pediatric patients with TBI on PICU. Very preliminary evidence suggests good tolerability of auditory stimuli, but efficacy of auditory stimuli to enhance delta waves remains unclear and requires further investigation. However, only low numbers of severe TBI patients could be enrolled in the study and, thus, future studies should consider an international multicentre approach.

Biological and Neurobiological Mechanisms of Transcranial Direct Current Stimulation.

Objective: Changes in cortical excitability and neuroplasticity are important parts of the neuropathology and pathophysiology of many neuropsychiatric disorders. Noninvasive brain stimulation is a high-potential therapeutic approach to modify cortical activities. One of the most popular of these techniques is transcranial direct current stimulation (tDCS). However, the biological and neurobiological effects of tDCS should be better clarified to enable its optimal use in clinical and therapeutic practices. In this paper, we summarize the neurophysiological and physiological effects and mechanisms of action of tDCS. Method : An update literature review was conducted on the biological responses of tDCS reported in human, in vitro and in vivo studies, with a focus on cellular cascades related to neuroplasticity, neuronal reorganization and inflammation caused by applied direct current electric fields. Results: The regulatory mechanisms of tDCS on motor and cognitive functions can be described by membrane polarization and transmembrane potential with a main subsequent effect on neurotransmission systems, neuronal excitability, synaptic microenvironment and neuronal connectivity to neuronal reorganization and neurogenesis in association with synaptic plasticity as well as inflammatory processes. In general, the effects of tDCS may include acute- or after-effects and direct or indirect effects and can be examined at different levels including the neurochemical, the neuroelectrical and the brain oscillatory levels. Conclusion: A deep understanding of the molecular and cellular responses to tDCS is very important and crucial. This therapeutic technique can be utilized in various clinical trials with a perspective of being routinely suggested and presented to patients with different pathological conditions influencing the central or peripheral nervous system.

Neuronal Sprouting and Reorganization in Bone Tissue Infiltrated by Human Breast Cancer Cells.

BackgroundPain is a common complication for patients with metastatic bone disease. Animal models suggest that the pain, in part, is driven by pathological sprouting and reorganization of the nerve fibers innervating the bone. Here, we investigate how these findings translate to humans.MethodsBone biopsies were collected from healthy volunteers (n = 7) and patients with breast cancer and metastatic bone disease (permissions H-15000679, S-20180057 and S-20110112). Cancer-infiltrated biopsies were from patients without recent anticancer treatment (n = 10), patients with recent anticancer treatment (n = 10), and patients with joint replacement surgery (n = 9). Adjacent bone sections were stained for (1) protein gene product 9.5 and CD34, and (2) cytokeratin 7 and 19. Histomorphometry was used to estimate the area of bone marrow and tumor burden. Nerve profiles were counted, and the nerve profile density calculated. The location of each nerve profile within 25 μm of a vascular structure and/or cancer cells was determined.ResultsCancer-infiltrated bone tissue demonstrated a significantly higher nerve profile density compared to healthy bone tissue. The percentage of nerve profiles found close to vascular structures was significantly lower in cancer-infiltrated bone tissue. No difference was found in the percentage of nerve profiles located close to cancer between the subgroups of cancer-infiltrated bone tissue. Interestingly, no correlation was found between nerve profile density and tumor burden.ConclusionsTogether, the increased nerve profile density and the decreased association of nerve profiles to vasculature strongly suggests that neuronal sprouting and reorganization occurs in human cancer-infiltrated bone tissue.

Dysfunction of the Hippocampal-Lateral Septal Circuit Impairs Risk Assessment in Epileptic Mice.

Temporal lobe epilepsy, a chronic disease of the brain characterized by degeneration of the hippocampus, has impaired risk assessment. Risk assessment is vital for survival in complex environments with potential threats. However, the underlying mechanisms remain largely unknown. The intricate balance of gene regulation and expression across different brain regions is related to the structure and function of specific neuron subtypes. In particular, excitation/inhibition imbalance caused by hyperexcitability of glutamatergic neurons and/or dysfunction of GABAergic neurons, have been implicated in epilepsy. First, we estimated the risk assessment (RA) by evaluating the behavior of mice in the center of the elevated plus maze, and found that the kainic acid-induced temporal lobe epilepsy mice were specifically impaired their RA. This experiment evaluated approach-RA, with a forthcoming approach to the open arm, and avoid-RA, with forthcoming avoidance of the open arm. Next, results from free-moving electrophysiological recordings showed that in the hippocampus, ∼7% of putative glutamatergic neurons and ∼15% of putative GABAergic neurons were preferentially responsive to either approach-risk assessment or avoid-risk assessment, respectively. In addition, ∼12% and ∼8% of dorsal lateral septum GABAergic neurons were preferentially responsive to approach-risk assessment and avoid-risk assessment, respectively. Notably, during the impaired approach-risk assessment, the favorably activated dorsal dentate gyrus and CA3 glutamatergic neurons increased (∼9%) and dorsal dentate gyrus and CA3 GABAergic neurons decreased (∼7%) in the temporal lobe epilepsy mice. Then, we used RNA sequencing and immunohistochemical staining to investigate which subtype of GABAergic neuron loss may contribute to excitation/inhibition imbalance. The results show that temporal lobe epilepsy mice exhibit significant neuronal loss and reorganization of neural networks. In particular, the dorsal dentate gyrus and CA3 somatostatin-positive neurons and dorsal lateral septum cholecystokinin-positive neurons are selectively vulnerable to damage after temporal lobe epilepsy. Optogenetic activation of the hippocampal glutamatergic neurons or chemogenetic inhibition of the hippocampal somatostatin neurons directly disrupts RA, suggesting that an excitation/inhibition imbalance in the dHPC dorsal lateral septum circuit results in the impairment of RA behavior. Taken together, this study provides insight into epilepsy and its comorbidity at different levels, including molecular, cell, neural circuit, and behavior, which are expected to decrease injury and premature mortality in patients with epilepsy.

Temporal and spatial changes in synaptic vesicle glycoprotein 2A (SV2A) under kainic acid induced epileptogenesis: An autoradiographic study

Synaptic Vesicle Glycoprotein 2A (SV2A) has been proposed as a presynaptic marker in several neurological disorders. Not only is SV2A the target for the antiepileptic drug levetiracetam, but also considered a marker of mature pre-synapses. In this study, we aimed to assess the binding of [3H]UCB-J as a selective radioligand for SV2A to visualize and determine changes during different stages of epileptogenesis by in-vitro autoradiography in rat models of temporal lobe epilepsy. Two different kainic acid (KA) injection routes were used to model temporal lobe epilepsy in the rat; a systemic (10 mg/kg KA injected intraperitoneally) and a local model (1.875 mM KA injected intrahippocampally). Brain tissue was sampled at different time points after the initial status epilepticus and semi-quantitative [3H]UCB-J autoradiography was performed to determine temporal and spatial changes under the progression of epileptogenesis. A decrease in [3H]UCB-J binding was observed in many brain areas in the acute phases after both types of kainic acid administration. Peak reductions occurred slightly before in systemic-treated animals (within 3–10 days) than after local-treated animals (within 5–15 days). Interestingly in the systemic model, we observed a full restoration in the binding level 30 days after the treatment in most areas probably reflecting neuronal reorganization. However, after the local injection in the hippocampus, the binding in the hippocampus, and in temporal and piriform cortices did not return to basal levels. The time-course profile displayed lateralization in the local model. These results demonstrate changes in the amount of a presynaptic SV2A binding site after seizures and suggest that SV2A may have importance in eliciting spontaneous seizures and/or be a biomarker for epileptogenesis. The present study shows that SV2A is a biomarker of acute phase epileptogenesis in specific brain regions.

Activation-induced chromatin reorganization in neurons depends on HDAC1 activity.

Spatial chromatin organization is crucial for transcriptional regulation and might be particularly important in neurons since they dramatically change their transcriptome in response to external stimuli. We show that stimulation of neurons causes condensation of large chromatin domains. This phenomenon can be observed invitro in cultured rat hippocampal neurons as well as invivo in the amygdala and hippocampal neurons. Activity-induced chromatin condensation is an active, rapid, energy-dependent, and reversible process. It involves calcium-dependent pathways but is independent of active transcription. It is accompanied by the redistribution of posttranslational histone modifications and rearrangements in the spatial organization of chromosome territories. Moreover, it leads to the reorganization of nuclear speckles and active domains located in their proximity. Finally, we find that the histone deacetylase HDAC1 is the key regulator of this process. Our results suggest that HDAC1-dependent chromatin reorganization constitutes an important level of transcriptional regulation in neurons.

Rapid and Bihemispheric Reorganization of Neuronal Activity in Premotor Cortex after Brain Injury.

Brain injuries cause hemodynamic changes in several distant, spared areas from the lesion. Our objective was to better understand the neuronal correlates of this reorganization in awake, behaving female monkeys. We used reversible inactivation techniques to “injure” the primary motor cortex, while continuously recording neuronal activity of the ventral premotor cortex in the two hemispheres, before and after the onset of behavioral impairments. Inactivation rapidly induced profound alterations of neuronal discharges that were heterogeneous within each and across the two hemispheres, occurred during movements of either the affected or nonaffected arm, and varied during different phases of grasping. Our results support that extensive, and much more complex than expected, neuronal reorganization takes place in spared areas of the bihemispheric cortical network involved in the control of hand movements. This broad pattern of reorganization offers potential targets that should be considered for the development of neuromodulation protocols applied early after brain injury.SIGNIFICANCE STATEMENT It is well known that brain injuries cause changes in several distant, spared areas of the network, often in the premotor cortex. This reorganization is greater early after the injury and the magnitude of early changes correlates with impairments. However, studies to date have used noninvasive brain imaging approaches or have been conducted in sedated animals. Therefore, we do not know how brain injuries specifically affect the activity of neurons during the generation of movements. Our study clearly shows how a lesion rapidly impacts neurons in the premotor cortex of both hemispheres. A better understanding of these complex changes can help formulate hypotheses for the development of new treatments that specifically target neuronal reorganization induced by lesions in the brain.

Biomarkers of response to rapid-acting antidepressants

Non-Invasive Brain Stimulation (NIBS) techniques and in particular, repetitive Transcranial Magnetic Stimulation (rTMS), are developing beyond mere clinical application. Although originally purposed for the treatment of resistant neuropsychiatric disorders, NIBS is also contributing to a deeper understanding of psychiatric disorders.rTMS is also changing the model of the disorder itself, from “mental” to one of neural connectivity. TMS allows the assessment of brain circuit excitability and eventually, of plastic changes affecting these circuits. While a clinical translational approach is, at the present time, the most adequate to meet the dimensional-circuit base model of the disorder, it refines the standard categorical classification of psychiatric disorders.The discovery of the fundamental importance of the balance between neuroplasticity and inflammation is also now explored through neuro-modulation findings consistently with the evidence of anti-inflammatory actions of the magnetic pulses.rTMS may activate, inhibit, or otherwise interfere with the activity of neuronal cortical networks, depending on stimulus frequency and intensity of brain-induced electric field. Of particular interest, yet still unclear, is how the relatively unspecific nature of TMS stimulation may lead to specific neuronal reorganization, as well as a definition of the TMS-triggered reorganization of functional brain modules, raising attention on the importance of the active participation of the patient to the treatment..Configuration and state of consciousness of the subject have made subjective experience under treatment regain importance in the neuro-scientific Psychiatry based on the requirement of United States National Institute of Health (NIH) and the substantial importance of the consciousness state in the efficacy of the TMS treatment. By focusing on the subjective experience, a renaissance of the phenomenology offers Psychiatry an opportunity to become proficient and to distinguish itself from other disciplines.For all these reasons, TMS should be included in the cluster of the sub-specialties as a new “Super-Specialty” and an appropriate training course has to be inaugurated. Psychiatrists are nowadays multi-specialists, moving from a specialty to another, vs super-specialist. The cultivation of a properly trained cohort of TMS psychiatrists will better meet the challenges of treatment-resistant psychiatric conditions (disorders of connectivity), through appropriate and ethical practice, meanwhile facilitating an informed development and integration of additional emerging neuro-modulation techniques. The aim of this consensus paper is to underline the interdisciplinary nature of NIBS, that also encompasses the subjective experience and to point out the necessity of a neuroscience-applied approach to NIBS in the context of the European College of Neuro-psychopharmacology (ECNP).

Manifesto for an ECNP Neuromodulation Thematic Working Group (TWG): Non-invasive brain stimulation as a new Super-subspecialty

Non-Invasive Brain Stimulation (NIBS) techniques and in particular, repetitive Transcranial Magnetic Stimulation (rTMS), are developing beyond mere clinical application. Although originally purposed for the treatment of resistant neuropsychiatric disorders, NIBS is also contributing to a deeper understanding of psychiatric disorders.rTMS is also changing the model of the disorder itself, from “mental” to one of neural connectivity. TMS allows the assessment of brain circuit excitability and eventually, of plastic changes affecting these circuits. While a clinical translational approach is, at the present time, the most adequate to meet the dimensional-circuit base model of the disorder, it refines the standard categorical classification of psychiatric disorders.The discovery of the fundamental importance of the balance between neuroplasticity and inflammation is also now explored through neuro-modulation findings consistently with the evidence of anti-inflammatory actions of the magnetic pulses.rTMS may activate, inhibit, or otherwise interfere with the activity of neuronal cortical networks, depending on stimulus frequency and intensity of brain-induced electric field. Of particular interest, yet still unclear, is how the relatively unspecific nature of TMS stimulation may lead to specific neuronal reorganization, as well as a definition of the TMS-triggered reorganization of functional brain modules, raising attention on the importance of the active participation of the patient to the treatment..Configuration and state of consciousness of the subject have made subjective experience under treatment regain importance in the neuro-scientific Psychiatry based on the requirement of United States National Institute of Health (NIH) and the substantial importance of the consciousness state in the efficacy of the TMS treatment. By focusing on the subjective experience, a renaissance of the phenomenology offers Psychiatry an opportunity to become proficient and to distinguish itself from other disciplines.For all these reasons, TMS should be included in the cluster of the sub-specialties as a new “Super-Specialty” and an appropriate training course has to be inaugurated. Psychiatrists are nowadays multi-specialists, moving from a specialty to another, vs super-specialist. The cultivation of a properly trained cohort of TMS psychiatrists will better meet the challenges of treatment-resistant psychiatric conditions (disorders of connectivity), through appropriate and ethical practice, meanwhile facilitating an informed development and integration of additional emerging neuro-modulation techniques. The aim of this consensus paper is to underline the interdisciplinary nature of NIBS, that also encompasses the subjective experience and to point out the necessity of a neuroscience-applied approach to NIBS in the context of the European College of Neuro-psychopharmacology (ECNP).

Monitoring of Motor Nerve Function Rehabilitation in Patients with Upper Extremity Hemiplegia Based on Functional Magnetic Resonance Imaging

Through functional magnetic resonance imaging (fMRI) technology, it is planned to use complex brain network technology to track brain functional imaging tracking treatment of stroke hemiplegia with scalp acupuncture. Functional magnetic resonance imaging (fMRI) can continuously monitor the rehabilitation process of motor nerve function in patients with stroke and upper limb hemiplegia, and explore the mechanism of brain plasticity changes at different levels of neural function cortex, motor function neural circuit, and behavior level. First, the fMRI test uses a block design, and the subjects complete the movement of the thumb and index finger. After completing the dysfunction assessment, fMRI data collection was performed on the patient before the CIMT treatment using a magnetic resonance apparatus, and a second fMRI data collection was performed 2 weeks after the CIMT treatment; only one fMRI data collection was performed on the volunteers. The functional magnetic resonance data was processed using the AFNI software package, and the functional scores of subjects were calculated using SPSS software. Second, studying the remodeling of residual brain tissue and functional compensation pathways can help to further clarify the recovery mechanism of motor function after stroke hemiplegia. Finally, compulsory exercise therapy can effectively improve upper limb motor dysfunction in stroke patients. The forced use of upper extremities during treatment induces the reorganization and compensation of cerebral cortical functional areas. This change in brain functional areas is consistent with the increase of upper extremity movement and improvement of motor function, fMRI can provide neuronal reorganization after exercise therapy evidence with compensation.

Neurostimulation for Stroke Rehabilitation.

Neurological injuries such as strokes can lead to important loss in motor function. Thanks to neuronal plasticity, some of the lost functionality may be recovered over time. However, the recovery process is often slow and incomplete, despite the most effective conventional rehabilitation therapies. As we improve our understanding of the rules governing activity-dependent plasticity, neuromodulation interventions are being developed to harness neural plasticity to achieve faster and more complete recovery. Here, we review the principles underlying stimulation-driven plasticity as well as the most commonly used stimulation techniques and approaches. We argue that increased spatiotemporal precision is an important factor to improve the efficacy of neurostimulation and drive a more useful neuronal reorganization. Consequently, closed-loop systems and optogenetic stimulation hold theoretical promise as interventions to promote brain repair after stroke.