Mitochondrial Metabolism in Major Depressive Disorder: From Early Diagnosis to Emerging Treatment Options.

Major Depressive Disorder (MDD) is one of the most disabling diseases in the world. MDD is traditionally diagnosed based on a patient's symptoms, which can lead to misdiagnosis. Although the pathogenic mechanisms of MDD are unknown, several studies have identified mitochondrial dysfunction as a central factor in the onset and progression of MDD. In the context of MDD, alterations in mitochondrial metabolism can lead to imbalances in energy production and oxidative stress, contributing to the disorder´s underlying pathophysiological mechanisms. Consequently, the identification of mitochondrial dysfunction as a key biomarker for early and accurate diagnosis of MDD represents a significant challenge. Faced with the limits of traditional treatments with antidepressants, new pharmacological therapeutic targets are being investigated such as ketamine/esketamine, psychedelics, or anti-inflammatories. All of these drugs show potential antidepressant effects due to their speed of action and ability to modulate neuroplasticity and/or motor processing. In parallel, non-pharmacological therapeutic targets are studied, like Transcranial Magnetic Stimulation (TMS) and Deep Brain Stimulation (DBS), recognized for their ability to modulate neuronal activity and offer treatment alternatives. As cellular activity is directly related to mitochondrial respiration, the aim of this review is examining the link between mitochondrial dysfunction and MDD, assessing how mitochondrial biomarkers could provide a more objective and precise diagnostic tool, and exploring other treatments in addition to traditional antidepressants, with a specific focus on emerging therapeutic targets. Finally, a detailed analysis of the strengths, weaknesses, opportunities, and threats of these approaches was carried out, highlighting the key challenges that must be addressed.

Visual Neuroprosthesis - Stimulation of Visual Cortical Centers in The Brain. Design of Non-Invasive Transcranial Stimulation of Functional Neurons.

PURPOSE: The purpose of the article is to present the history and current status of visual cortical neuroprostheses, and to present a new method of stimulating intact visual cortex cells. METHODS: This paper contains an overview of the history and current status of visual cortex stimulation in severe visual impairment, but also highlights its shortcomings. These include mainly the stimulation of currently damaged cortical cells over a small area and, from a morphological point of view, possible damage to the stimulated neurons by the electrodes and their encapsulation by gliotic tissue. RESULTS: The paper also presents a proposal for a new technology of image processing and its transformation into a form of non-invasive transcranial stimulation of undamaged parts of the brain, which is protected by a national and international patent. CONCLUSION: The paper presents a comprehensive review of the current options for compensating for lost vision at the level of the cerebral cortex and a proposal for a new non-invasive method of stimulating the functional neurons of the visual cortex.

Novel approaches to motoneuron disease/ALS treatment using non-invasive brain and spinal stimulation: IFCN handbook chapter.

Non-invasive brain stimulation techniques have been exploited in motor neuron disease (MND) with multifold objectives: to support the diagnosis, to get insights in the pathophysiology of these disorders and, more recently, to slow down disease progression. In this review, we consider how neuromodulation can now be employed to treat MND, with specific attention to amyotrophic lateral sclerosis (ALS), the most common form with upper motoneuron (UMN) involvement, taking into account electrophysiological abnormalities revealed by human and animal studies that can be targeted by neuromodulation techniques. This review article encompasses repetitive transcranial magnetic stimulation methods (including low-frequency, high-frequency, and pattern stimulation paradigms), transcranial direct current stimulation as well as experimental findings with the newer approach of trans-spinal direct current stimulation. We also survey and discuss the trials that have been performed, and future perspectives.

Modulation of cerebellar cortical, cerebellar nuclear and vestibular nuclear activity using alternating electric currents.

Introduction: Cerebellar transcranial alternating current stimulation (ctACS) has shown promise as a therapeutic modality for treating a variety of neurological disorders, and for affecting normal learning processes. Yet, little is known about how electric fields induced by applied currents affect cerebellar activity in the mammalian cerebellum under in vivo conditions. Methods: Alternating current (AC) stimulation with frequencies from 0.5 to 20 Hz was applied to the surface of the cerebellum in anesthetized rats. Extracellular recordings were obtained from Purkinje cells (PC), cerebellar and vestibular nuclear neurons, and other cerebellar cortical neurons. Results and discussion: AC stimulation modulated the activity of all classes of neurons. Cerebellar and vestibular nuclear neurons most often showed increased spike activity during the negative phase of the AC stimulation. Purkinje cell simple spike activity was also increased during the negative phase at most locations, except for the cortex directly below the stimulus electrode, where activity was most often increased during the positive phase of the AC cycle. Other cortical neurons showed a more mixed, generally weaker pattern of modulation. The patterns of Purkinje cell responses suggest that AC stimulation induces a complex electrical field with changes in amplitude and orientation between local regions that may reflect the folding of the cerebellar cortex. Direct measurements of the induced electric field show that it deviates significantly from the theoretically predicted radial field for an isotropic, homogeneous medium, in both its orientation and magnitude. These results have relevance for models of the electric field induced in the cerebellum by AC stimulation.

Predictive value of IOM in clipping of unruptured intracranial aneurysms - A prospective study from the surgeon's point of view.

Introduction: Intraoperative neuromonitoring (IOM) of motor/somatosensory evoked potentials is a well-established approach for reducing ischemic complications after aneurysm clipping. Research question: To determine the predictive validity of IOM for postoperative functional outcome and its perceived added value for intraoperative real-time feedback of functional impairment in the surgical treatment of unruptured intracranial aneurysms (UIAs). Material and methods: Prospective study of patients scheduled for elective clipping of UIAs between 02/2019-02/2021. Transcranial motor evoked potentials (tcMEP) were used in all cases, a significant decline was defined as loss of ≥50% in amplitude or 50% latency increase. Clinical data were correlated to postoperative deficits. A surgeon's questionnaire was conceived. Results: 47 patients were included, median age 57 years (range 26-76). IOM was successful in all cases. In 87.2%, IOM was stable throughout surgery, although 1 patient (2.4%) demonstrated a permanent postoperative neurological deficit. All patients with an intraoperatively reversible tcMEP-decline (12.7%) showed no surgery-related deficit, regardless of the decline duration (range 0.5-40.0 â€‹min; mean: 13.8). Temporary clipping (TC) was performed in 12 cases (25.5%), with a decline in amplitude in 4 patients. After clip-removal, all amplitudes returned to baseline. IOM provided the surgeon with a higher sense of security in 63.8%. Discussion and conclusion: IOM remains invaluable during elective microsurgical clipping, particularly during TC of MCA and AcomA-aneurysms. It alerts the surgeon of impending ischemic injury and offers a way of maximizing the time frame for TC. IOM has highly increased surgeons' subjective feeling of security during the procedure.

Usefulness of Transcranial Motor Evoked Potential in Clipping Surgery for Cerebral Aneurysms-Introduction of a New Protocol for Stable Monitoring.

The usefulness of transcranial motor evoked potentials (Tc-MEPs) in clipping surgery has been reported. However, numerous false positive and false negative cases were reported. We report the usefulness of a new protocol compared with direct cortical MEP (Dc-MEP).Materials were 351 patients who underwent aneurysmal clipping under simultaneous monitoring of Tc- and Dc-MEPs. A total of 337 patients without hemiparesis and 14 with hemiparesis were separately analyzed. Intraoperative changes of Tc-MEP thresholds were examined in the first 50 patients without hemiparesis. The stimulation strength of Tc-MEP was set at +20% of the stimulation threshold. As thresholds changed intraoperatively, thresholds were examined every 10 min and changed stimulation strength.Stimulation thresholds of Tc-MEP were significantly decreased after craniotomy and significantly increased after CSF aspiration. The recording ratios of Tc- and Dc-MEPs were 98.8% and 90.5%, respectively. Out of 304 patients without MEP change, 5 patients developed transient or mild hemiparesis with infarction of the territory of the perforating artery arising from the posterior communicating artery. Out of 31 patients whose MEP transiently disappeared, 3 patients developed transient or mild hemiparesis. The other two patients without MEP recovery manifested persistent hemiparesis. In 14 patients with preoperative hemiparesis, 3 patients whose healthy/affected ratio of Tc-MEP was large developed severe persistent hemiparesis.We clarified the intraoperative changes of Tc-MEP thresholds for the first time. A new protocol of Tc-MEP that followed thresholds and changed stimulation strength to +20% of thresholds is useful for stable monitoring. The usefulness of Tc-MEP is the same as that or better than that of Dc-MEP.

Non-invasive Brain Stimulation in Post-stroke Dysphagia Rehabilitation: A Narrative Review of Meta-analyses in 2022.

Objectives: This study aimed to update the current knowledge on non-invasive brain stimulation (NIBS) effects, such as repetitive transcranial brain stimulation and transcranial direct current stimulation, in patients with post-stroke dysphagia (PSD). Methods: We summarized the basic principles and therapeutic strategies of NIBS. We then reviewed nine meta-analyses from 2022 that investigated the efficacy of NIBS in PSD rehabilitation. Results: Although dysphagia is a common and devastating sequela of stroke, the efficacy of conventional swallowing therapies remains controversial. NIBS techniques have been proposed as promising approaches for managing PSD via neuromodulation. Recent meta-analyses have shown that NIBS techniques are beneficial for the recovery of patients with PSD. Conclusions: NIBS has the potential to become a novel alternative treatment for PSD rehabilitation.

Termination of seizures by ictal transcranial focal cortex stimulation.

Whereas high-level evidence exists on chronic neuromodulatory effects of different brain stimulation approaches in reducing seizure frequency, evidence for acute antiseizure effects of electrical brain stimulation during seizures is sparse. As part of an ongoing trial, we implanted a patient with a novel focal cortex stimulation (FCS) device with a Laplacian electrode placed over a precentral focal cortical dysplasia. The baseline seizure frequency was 125 per month, consisting of (i) focal aware sensory seizures that invariably progressed to uni- or bilateral tonic contraction and clonic jerking, and (ii) primary motor seizures. Besides an overall reduction in seizure frequency, on-demand stimulation had an immediate effect on seizures with a sensory phase, whereby 63%-86% of these seizures were terminated by ictal stimulation. These observations provide the first evidence that ictal self-triggered transcranial focal cortex stimulation can significantly interfere with the progression of seizure semiology.

Estimulação Transcraniana para Transtornos do Sono: uma revisão sistemática / Transcranial Stimulation in Sleep Disorders: a systematic review / Estimulación Transcraneal para los Trastornos del Sueño: una revisión sistemática

Os transtornos do sono podem ter várias consequências para a cognição, comportamento e vida social das pessoas. No entanto, a terapia utilizada para avaliar e intervir nesses transtornos ainda não está consolidada. Nesse contexto, o objetivo deste estudo foi verificar a aplicabilidade e eficácia da estimulação transcraniana (ETCA / ETCC / EMTr) nos transtornos do sono. Foi realizada uma busca sistemática de acordo com as diretrizes do PRISMA nas bases de dados Web of Science, PubMed, LILACS e SciELO. Inicialmente, foram encontrados 448 artigos, de acordo com os critérios de elegibilidade. O banco de dados de evidências de fisioterapia (PEDro) foi utilizado para avaliar a qualidade metodológica dos 11 artigos finais. Em geral, os resultados indicam que há tanto relatos favoráveis quanto desfavoráveis à eficácia do uso terapêutico das técnicas de estimulação transcraniana nos transtornos do sono e, portanto, ainda se configura como uma questão em aberto, dependendo de múltiplos fatores metodológicos e conceituais.

Sleep disorders can have several consequences on people's cognition, behavior and social life. However, the therapy used to assess and intervene in these disorders is not yet consolidated. In this context, the aim of this study was to verify the applicability and effectiveness of transcranial stimulation (tACS / tDCS / rTMS) in sleep disorders. A systematic search was performed according to PRISMA guidelines in the Web of Science, PubMed, LILACS, and SciELO databases. Initially, 448 articles were found, according to the eligibility criteria. The physiotherapy evidence database (PEDro) was used to assess the methodological quality of the 11 final articles. In general, the results indicate that there are both favorable and unfavorable reports on the effectiveness of the therapeutic use of transcranial stimulation techniques in sleep disorders and, therefore, it is still an open question, depending on multiple methodological and conceptual factors.

Trastornos del sueño pueden tener varias consecuencias para la cognición, el comportamiento y la vida social de las personas. La terapia utilizada para evaluar e intervenir en estos trastornos aún no está consolidada. En este contexto, el objetivo de este estudio fue verificar la aplicabilidad y efectividad de la estimulación transcraneal (ETCA / ETCC / EMTr) en los trastornos del sueño. Se realizó una búsqueda sistemática según las guías PRISMA en las bases de datos Web of Science, PubMed, LILACS y SciELO. Inicialmente se encontraron 448 artículos, según los criterios de elegibilidad. Se utilizó la base de datos PEDro para evaluar la calidad metodológica de los 11 artículos finales. En general, los resultados indican que existen informes tanto favorables como desfavorables sobre la efectividad del uso terapéutico de las técnicas de estimulación transcraneal en los trastornos del sueño y, por tanto, sigue siendo una cuestión abierta, dependiendo de múltiples factores metodológicos y conceptuales.

Targeting Three Brain Regions (Bilateral SMA, Left and Right DLPFC) Sequentially in One Session Using Combined Repetitive Transcranial Magnetic Stimulation and Intermittent Theta-burst Stimulation in Treatment-refractory Obsessive-compulsive Disorder: A Case Report.

Repetitive transcranial magnetic stimulation (rTMS) has been widely used as a therapy for refractory obsessive-compulsive disorder (OCD). However, it remains unclear which exact target and stimulation sequence of rTMS is most effective for OCD. Here, we report the case of an 18-year-old female with treatment-refractory OCD whose symptoms markedly improved after combined rTMS and intermittent theta-burst stimulation over the bilateral dorsolateral prefrontal cortex and supplementary motor area. Our report indicates that combining treatment sequences that stimulate different brain regions sequentially is feasible and may clinically benefit patients suffering from OCD.

Using High-Definition Transcranial Alternating Current Stimulation to Treat Patients with Fibromyalgia: A Randomized Double-Blinded Controlled Study.

Objectives: This study aimed to investigate the safety and efficacy of high-definition transcranial alternating current stimulation (HD-tACS) to the left primary motor cortex (M1) in the treatment of fibromyalgia (FM) patients. Methods: In this randomized, double-blind, sham-controlled clinical trial, patients with FM were recruited in a teaching hospital. Thirty-eight patients were randomized to active HD-tACS (n = 19) or sham stimulation (n = 19). Active stimulation included a daily session of 20-min stimulation of 1 mA HD-tACS over the left M1 for ten sessions in two weeks. The primary outcome was the change in pain intensity and quality of life, assessed using the numeric rating scale (NRS) and the fibromyalgia impact questionnaire (FIQ) at baseline and after two weeks of treatment. Secondary outcomes included other core symptoms of FM (psychological distress, sleep quality, hyperalgesia measured by pressure pain threshold) and changes in biomarkers' total Tau and Aß1-42. All analyses were based on intention-to-treat for a significance level of p < 0.05. Results: Of the 38 randomized patients, 35 completed the study. After two weeks, HD-tACS induced a significant reduction in FIQ score post-treatment. However, there were no significant differences in NRS and FIQ scores compared to sham stimulation. Most adverse events were mild in severity. Nevertheless, one patient receiving HD-tACS attempted suicide during the trial. Conclusions: These results suggest that HD-tACS may effectively reduce pain, psychological distress, and symptom impacts in FM patients. However, we found no significant differences between the two groups. Future studies investigating HD-tACS in FM are warranted.

Effects of Repetitive Transcranial Magnetic Stimulation on Gait and Postural Control Ability of Patients with Executive Dysfunction after Stroke.

Objective: To assess the effects of repetitive transcranial magnetic stimulation (rTMS) on the gait and postural control ability of patients with executive dysfunction (ED) after stroke. Methods: A total of 18 patients with ED after stroke were randomly assigned into two groups, including an experimental group and a sham group. Patients in both groups received routine rehabilitation therapy, and patients in the experimental group underwent rTMS on the left dorsolateral prefrontal cortex (DLPFC) for 2 weeks (5 HZ, 80%MT, 1200 pulses). In the sham group, patients experienced sham stimulation treatment, in which the coil was placed vertically with the head. Before and after treatment, patients in both groups were subjected to Montreal cognitive assessment (MoCA) scoring, Fugl−Meyer assessment of lower extremity (L-FMA), Stroop color-word test (SCWT), gait analysis, foot plantar pressure test, 10-m walking test (10MWT), Berg balance scale (BBS), and timed up and go test (TUGT). In the SCWT, it was attempted to record the time of each card (SCWT-T), the correct number (SCWT-C), Stroop interference effect-time (SIE-T), and SIE correct count (SIE-C). The TUGT was categorized into four stages: getting up (GT), walking straight (WT), turning around (TT), and sitting down (ST), in which the total time of TUGT was calculated. Results: After two weeks of treatment, the evaluation indexes were improved in the two groups, some of which were statistically significant. In the experimental group, SCWT-T, SIE-T, SIE-C, GT, WT, TT, ST, and TUGT were significantly improved after treatment (p < 0.05). SCWT-C, L-FMA score, 10MWT, GT, WT, stride length, step width, foot plantar pressure, pressure center curve, and activities of daily living were not statistically different from those before treatment (p > 0.05). After treatment, SCWT-T, SIE-C, SIE-T, BBS score, TT, and ST in the experimental group were significantly shorter than those before treatment, with statistical differences (p < 0.05). Compared with the sham group, SCWT-C, L-FMA score, 10MWT, GT, WT, TUGT, stride length, step width, foot plantar pressure, pressure center curve, and motor skills were not significantly improved (p > 0.05). Conclusion: It was revealed that post-stroke rTMS treatment of patients with ED could improve executive function, improve postural control function, and reduce the risk of falling. In addition, rTMS of DLPFC could be a therapeutic target for improving postural control ability and reducing the risk of falling.

Transcranial Magnetic Stimulation and Transcranial Electrical Stimulation in Horses.

Depending on the localization of the lesion, spinal cord ataxia is the most common type of ataxia in horses. Most prevalent diagnoses include cervical vertebral stenotic myelopathy (CVSM), equine protozoal myeloencephalitis (EPM), trauma and equine degenerative myeloencephalopathy (EDM). Other causes of ataxia and weakness are associated with infectious causes, trauma and neoplasia. A neurologic examination is indispensable to identify the type of ataxia. In addition, clinical neurophysiology offers tools to locate functional abnormalities in the central and peripheral nervous system. Clinical EMG assessment looks at the lower motoneuron function (LMN) and is used to differentiate between neuropathy in peripheral nerves, which belong to LMNs and myopathy. As LMNs reside in the spinal cord, it is possible to grossly localize lesions in the myelum by muscle examination. Transcranial (tc) stimulation techniques are gaining importance in all areas of medicine to assess the motor function of the spinal cord along the motor tracts to the LMNs. Applications in diagnostics, intraoperative neurophysiological monitoring (IONM), and evaluation of effects of treatment are still evolving in human medicine and offer new challenges in equine medicine. Tc stimulation techniques comprise transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES). TMS was first applied in horses in 1996 by Mayhew and colleagues and followed by TES. The methods are exchangeable for clinical diagnostic assessment but show a few differences. An outline is given on the principles, current clinical diagnostic applications and challenging possibilities of muscle evoked potentials (MEP) from transcranial stimulation in horses.

O uso da estimulação transcraniana como tratamento na reabilitação motora de criança com paralisia cerebral - projeto de estudo de caso / El uso de la estimulación transcraneal como tratamiento en la rehabilitación motora de un niño con parálisis cerebral -un proyecto de estudio de caso / The use of transcranial stimulation as a treatment in the motor rehabilitation of a child with cerebral palsy -a case study projec

RESUMO A Paralisia Cerebral (PC) também denominada como encefalopatia crônica não-progressiva da infância é consequência de lesões não progressivas que aconteceram no cérebro imaturo no período pré, peri ou pós-natal, afetando o sistema nervoso central em fase de maturação estrutural e funcional. O presente trabalho trata-se de um estudo de caso com características de Pesquisa Experimental, Intervencional, onde foi realizado um protocolo de duas sessões semanais, com tempo de atendimento de 40 minutos, num total de 20 (vinte) sessões. O protocolo terapêutico consistiu de estimulação transcraniana e teve como objetivo geral investigar os efeitos da ETCC, associada à cinesioterapia e ativação dos neurônios espelhos, na reabilitação de uma criança com paralisia cerebral, sexo masculino, 54 meses de idade cronológica, grau moderado de hipotonia muscular em membros inferiores, movimentos voluntários com debilidade de força muscular; escoliose dorso-lombar e pontuação zero na Escala de Mobilidade Funcional e Asworth Modificada. O Sistema de Classificação da Função Motora Grossa (GMFCS) apresentou-se com classificação nível V, limitação na habilidade de manter as posturas anti-gravitacionais da cabeça e tronco e de controlar os movimentos de braços e pernas. Índice de Barthel Modificado com pontuação 11- classificação de dependência severa. A escala Denver II com prejuízos significativos nos domínios: pessoal-social, motor fino adaptativo, linguagem e motor grosso.

RESUMEN La parálisis cerebral (PC) también denominada como encefalopatía crónica no progresiva de la infancia es consecuencia de lesiones no progresivas que ocurrieron en el cerebro inmaduro en el periodo pre, peri o post-natal, afectando el sistema nervioso central en la fase de maduración estructural y funcional. El presente trabajo trata de un estudio de caso con características de investigación experimental, intervencional, donde fue realizado un protocolo de dos sesiones semanales de cuarenta minutos, con un total de veinte (20) sesiones. El protocolo terapéutico consistió en una estimulación transcraniana y tuvo como objetivo general, investigar los efectos de la ETCC, asociada a la cinesioterapia y activación de las neuronas espejo, en la rehabilitación de un niño con parálisis cerebral de 54 meses de edad cronológica, grado moderado de hipertonía muscular en miembros inferiores, movimientos voluntarios con debilidad de fuerza muscular; escoliosis dorsolumbar y puntuación cero en la escala de Movilidad Fun.

ABSTRACT Cerebral Palsy (CP) also known as chronic non-progressive encephalopathy of childhood is a consequence of non-progressive lesions that occurred in the immature brain in the pre, peri or postnatal period, affecting the central nervous system in a phase of structural maturation and functional. The present work is a case study with characteristics of Experimental, Interventional Research, where a protocol of two weekly sessions was carried out, with a service time of 40 minutes, in a total of 20 (twenty) sessions. The therapeutic protocol consisted of transcranial stimulation and aimed to investigate the effects of tDCS, associated with kinesiotherapy and activation of mirror neurons, in the rehabilitation of a 54-month-old male child with cerebral palsy, moderate degree of muscular hypotonia in the lower limbs, voluntary movements with weak muscular strength; dorsolumbar scoliosis and zero score on the Functional Mobility and Modified Asworth Scale. The Gross Motor Function Classification System (GMFCS) has a level V classification, limiting the ability to maintain antigravity postures of the head and trunk and to control arm and leg movements. Modified Barthel Index with score 11- severe dependency rating. The Denver II scale with significant impairments in the following domains: personal-social, adaptive fine motor, language and gross motor.

Trapezius Motor Evoked Potentials From Transcranial Electrical Stimulation and Transcranial Magnetic Stimulation: Reference Data, Characteristic Differences and Intradural Motor Velocities in Horses.

Reason for Performing Study: So far, only transcranial motor evoked potentials (MEP) of the extensor carpi radialis and tibialis cranialis have been documented for diagnostic evaluation in horses. These allow for differentiating whether lesions are located in either the thoraco-lumbar region or in the cervical myelum and/or brain. Transcranial trapezius MEPs further enable to distinguish between spinal and supraspinal located lesions. No normative data are available. It is unclear whether transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) are interchangeable modalities. Objectives: To provide normative data for trapezius MEP parameters in horses for TES and TMS and to discern direct and indirect conduction routes by neurophysiological models that use anatomical geometric characteristics to relate latency times with peripheral (PCV) and central conduction velocities (CCV). Methods: Transcranial electrical stimulation-induced trapezius MEPs were obtained from twelve horses. TES and TMS-MEPs (subgroup 5 horses) were compared intra-individually. Trapezius MEPs were measured bilaterally twice at 5 intensity steps. Motoneurons were localized using nerve conduction models of the cervical and spinal accessory nerves (SAN). Predicted CCVs were verified by multifidus MEP data from two horses referred for neurophysiological assessment. Results: Mean MEP latencies revealed for TES: 13.5 (11.1-16.0)ms and TMS: 19.7 (12-29.5)ms, comprising ∼100% direct routes and for TMS mixed direct/indirect routes of L:23/50; R:14/50. Left/right latency decreases over 10 > 50 V for TES were: -1.4/-1.8 ms and over 10 > 50% for TMS: -1.7/-3.5 ms. Direct route TMS-TES latency differences were 1.88-4.30 ms. 95% MEP amplitudes ranges for TES were: L:0.26-22 mV; R:0.5-15 mV and TMS: L:0.9 - 9.1 mV; R:1.1-7.9 mV. Conclusion: This is the first study to report normative data characterizing TES and TMS induced- trapezius MEPs in horses. The complex trapezius innervation leaves TES as the only reliable stimulation modality. Differences in latency times along the SAN route permit for estimation of the location of active motoneurons, which is of importance for clinical diagnostic purpose. SAN route lengths and latency times are governed by anatomical locations of motoneurons across C2-C5 segments. TES intensity-dependent reductions of trapezius MEP latencies are similar to limb muscles while MEP amplitudes between sides and between TES and TMS are not different. CCVs may reach 180 m/s.

The Effectiveness of Transcranial Stimulation in Improving Swallowing Outcomes in Adults with Poststroke Dysphagia: A Systematic Review and Meta-analysis.

Transcranial stimulation has been proposed as an alternative rehabilitation therapy for adults with post-stroke dysphagia (PSD). This systematic review sought to determine the effectiveness of transcranial stimulation in patients with post-stroke dysphagia to improve swallowing function. From inception to January 3, 2021, an extensive search was conducted in PubMed, EMBASE, Cochrane, CINAHL, and Scopus, Web of Science. The randomized controlled trials (RCTs) included studies in adults aged 18 years and older who suffered from post-stroke dysphagia. Using Hedges' g as effect size, meta-analyses were conducted using random-effects models. To investigate potential sources of heterogeneity, subgroup analyses, and multivariable meta-regression analyses were conducted. Sixteen RCTs were included in this review, and 13 RCTs were used for meta-analysis. The meta-analysis showed that a large effect size in improving swallowing function after repetitive Transcranial Magnetic Stimulation (g = - 0.86, 95% CI - 1.57, - 0.16) and medium effect size in Transcranial Direct Current Stimulation (g = - 0.61, 95% CI - 1.04, - 0.17) at post-intervention, respectively. Subgroup and meta-regression analysis indicated that stimulation of the esophagus cortical area and middle-aged adults had a greater effect on swallowing function. The overall certainty of evidence assessed using the GRADE approach was low. Despite the positive results, transcranial stimulation requires additional research to reach definitive conclusions about the optimal stimulation protocol and to achieve the greatest benefit. Future trials should be more rigorous and include a larger sample size to demonstrate the efficacy of transcranial stimulation. Transcranial stimulation enables a more efficacious approach to dysphagia mitigation in PSD rehabilitation.

Efficacy of repetitive transcranial magnetic stimulation (rTMS) for reducing consumption in patients with alcohol use disorders (ALCOSTIM): study protocol for a randomized controlled trial.

BACKGROUND: The number of people with an alcohol use disorder (AUD) was recently estimated to be 63.5 million worldwide. The global burden of disease and injury attributable to alcohol is considerable: about 3 million deaths, namely one in 20, were caused by alcohol in 2015. At the same time, AUD remains seriously undertreated. In this context, alternative or adjunctive therapies such as brain stimulation could play an important role. The early results of studies using repetitive transcranial magnetic stimulation (rTMS) suggest that stimulations delivered to the dorsolateral prefrontal cortex significantly reduce cravings and improve decision-making processes in various addictive disorders. We therefore hypothesize that rTMS could lead to a decrease in alcohol consumption in patients with AUD. METHODS/DESIGN: We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy of rTMS on alcohol reduction in individuals diagnosed with AUD. The study will be conducted in 2 centers in France. Altogether, 144 subjects older than 18 years and diagnosed with AUD will be randomized to receive 5 consecutive twice-daily sessions of either active or sham rTMS (10 Hz over the right DLPFC, 2000 pulses per day). The main outcomes of the study will be changes in alcohol consumption within the 4 weeks after the rTMS sessions. Secondary outcome measures will include changes in alcohol consumption within the 24 weeks, alcohol cravings, clinical and biological improvements, effects on mood and quality of life, and cognitive and safety assessments, and, for smokers, an assessment of the effects of rTMS on tobacco consumption. DISCUSSION: Several studies have observed a beneficial effect of rTMS on substance use disorders by reducing craving, impulsivity, and risk-taking behavior and suggest that rTMS may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm this hypothesis. The results from this large randomized controlled trial will give a better overview of the therapeutic potential of rTMS in AUD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04773691. Registered on 26 February 2021 https://clinicaltrials.gov/ct2/show/NCT04773691?term=trojak&draw=2&rank=5 .

Tools to explore neuroplasticity in humans: Combining interventional neurophysiology with functional and structural magnetic resonance imaging and spectroscopy.

This chapter summarizes how brain imaging can be used in combination with non-invasive transcranial stimulation to probe and induce neuroplasticity in the human brain. We aim to give a conceptual account and highlight exemplary studies. We showcase the scientific and clinical potentials of studies focusing on the combination of transcranial magnetic stimulation (TMS) with Magnetic Resonance Imaging (MRI) or Magnetic Resonance Spectroscopy (MRS). MRI and MRS can be used before brain stimulation to identify target networks and loci but also to inform individual dosing. After a brain stimulation session, MRI and MRS can be used to pinpoint how the stimulation protocol alters brain function, structure, or metabolism and relate these after-effects to behavioral and clinical outcomes. Complementing these "offline" approaches, TMS can also be applied "online" during MRI or MRS to delineate how stimulation acutely engages the stimulated brain regions and networks. In this case, it is critical to account for confounds introduced by off-target stimulation of peripheral structures of the nervous system that may not only confound MR-based readouts but also induce neuroplastic phenomena.

Cerebellar stimulation in schizophrenia: A systematic review of the evidence and an overview of the methods.

Background: Cerebellar structural and functional abnormalities underlie widespread deficits in clinical, cognitive, and motor functioning that are observed in schizophrenia. Consequently, the cerebellum is a promising target for novel schizophrenia treatments. Here we conducted an updated systematic review examining the literature on cerebellar stimulation efficacy and tolerability for mitigating symptoms of schizophrenia. We discuss the purported mechanisms of cerebellar stimulation, current methods for implementing stimulation, and future directions of cerebellar stimulation for intervention development with this population. Methods: Two independent authors identified 20 published studies (7 randomized controlled trials, 7 open-label studies, 1 pilot study, 4 case reports, 1 preclinical study) that describe the effects of cerebellar circuitry modulation in patients with schizophrenia or animal models of psychosis. Published studies up to October 11, 2022 were identified from a search within PubMed, Scopus, and PsycInfo. Results: Most studies stimulating the cerebellum used transcranial magnetic stimulation or transcranial direct-current stimulation, specifically targeting the cerebellar vermis/midline. Accounting for levels of methodological rigor across studies, these studies detected post-cerebellar modulation in schizophrenia as indicated by the alleviation of certain clinical symptoms (mainly negative and depressive symptoms), as well as increased frontal-cerebellar connectivity and augmentation of canonical neuro-oscillations known to be abnormal in schizophrenia. In contrast to a prior review, we did not find consistent evidence for cognitive improvements following cerebellar modulation stimulation. Modern cerebellar stimulation methods appear tolerable for individuals with schizophrenia, with only mild and temporary side effects. Conclusion: Cerebellar stimulation is a promising intervention for individuals with schizophrenia that may be more relevant to some symptom domains than others. Initial results highlight the need for continued research using more methodologically rigorous designs, such as additional longitudinal and randomized controlled trials. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022346667].