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Transcranial magnetic stimulation (TMS) represents a distinctive technique for non-invasive brain stimulation. Recent advancements in image processing have enabled the enhancement of TMS by integrating magnetic resonance imaging (MRI) modalities with TMS via a neuronavigation system. The aim of this study is to assess the efficacy of navigated TMS for cortical mapping in comparison to surgical mapping using direct electrical stimulation (DES). This study involved 30 neurosurgical procedures for tumors located in or adjacent to the precentral gyrus. The DES points were compared with TMS responses based on the original distances of vectorial modules. There was a notable similarity in the points obtained from the two mapping methods. The distances between the geometric centers of TMS and DCS were 4.85 ± 1.89 mm. A strong correlation was identified between these vectorial points (r = 0.901, p < 0.001). The motor threshold in TMS was highest in the motor cortex adjacent to the tumor compared to the normal cortex (p < 0.001). Patients with deficits exhibited excellent accuracy in both methods. In view of this, TMS demonstrated reliable and precise application in brain mapping, which is a promising method for preoperative functional mapping in motor cortex tumor surgery.

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Introduction: Estimates of the worldwide increase in amputees raises the awareness to solve long-standing problems. Understanding the functional brain modifications after a lower limb amputation (LLA) is one of the first steps towards proposing new rehabilitation approaches. Functional modifications in the central nervous system due the amputation could be involved in prosthesis use failures and Phantom Limb Pain (PLP), increasing costs and overwhelming the health services. Objective: This study analyses orphan primary motor area (M1-Orphan) hemodynamic and metabolic behaviour, which previously controlled the limb that was amputated, in comparison with the M1-Preserved, responsible for the intact limb (IL) during phantom limb imagery moving during Mirror Therapy (MT), compared to Isolated Intact Limb Movement Task (I-ILMT). Methodology: A case-control study with unilateral traumatic LLA with moderate PLP who measured [oxy-Hb] and [deoxy-Hb] in the M1 area by Functional Near InfraredSpectroscopy (fNIRS) during the real (I-ILMT) and MT task. Results: Sixty-five patients, with 67.69% of men, young (40.32 ± 12.91), 65.63% amputated due motorcycle accidents, 4.71 ± 7.38 years ago, predominantly above the knee (57.14%). The M1 activation in the orphan cortex did not differ from the activation in the intact cortex during MT (P > .05). Conclusion: The perception of the Phantom limb moving or intact limb moving is metabolically equivalent in M1, even in the absence of a limb. In other words, the amputation does not alter the brain metabolism in control of phantom movement.

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This is the case report of a woman who started to write and read from right to left after anterior cerebral artery stroke, affecting the left supplementary motor area. No cases were found in the literature with exactly the same characteristics. She has been able to read and write faster after rehabilitation approach at Sarah Network of Rehabilitation Hospitals, in the Belo Horizonte city unit, Brazil, despite the maintenance of the inversion. She returned to her previous activities in an adaptive way. It was discussed how the dysfunction in this cerebral area and its connections may disturb the reading strategy and direction.

Relato do caso de uma mulher que passou a escrever e ler da direita para a esquerda após um acidente vascular encefálico isquêmico de artéria cerebral anterior, acometendo área motora suplementar esquerda. Não foram encontrados casos na literatura exatamente com as mesmas características. Durante a participação da paciente no programa de reabilitação neurológica da Rede Sarah de Hospitais de Reabilitação, unidade Belo Horizonte, foram observados ganhos na agilidade de leitura e escrita, ainda que mantendo a inversão, e retorno às suas atividades de forma adaptada. Realizou-se discussão de como o comprometimento dessa área e de suas conexões pode perturbar a estratégia de leitura e sua direção.

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BACKGROUND: Phantom pain limb (PLP) has gained more attention due to the large number of people with amputations around the world and growing knowledge of the pain process, although its mechanisms are not completely understood. OBJECTIVES: The aim of this study was to understand, in patients with amputations, the association between PLP and residual limb pain (RLP), and the brain metabolic response in cortical motor circuits, using functional near-infrared spectroscopy (fNIRS). METHODS: Sixty participants were recruited from the rehabilitation program in São Paulo, Brazil. Included patients were aged over 18 years, with traumatic unilateral lower-limb amputation, with PLP for at least 3 months after full recovery from amputation surgery. PLP and RLP levels were measured using visual analogue scales. fNIRS was performed during motor execution and motor mirror tasks for 20 s. In order to highlight possible variables related to variation in pain measures, univariate linear regression analyses were performed for both experimental conditions, resulting in four fNIRS variables (two hemispheres x two experimental conditions). Later, in order to test the topographic specificity of the models, eight multivariate regression analyses were performed (two pain scales x two experimental conditions x two hemispheres), including the primary motor cortex (PMC) related channel as an independent variable as well as five other channels related to the premotor area, supplementary area, and somatosensory cortex. All models were controlled for age, sex, ethnicity, and education. RESULTS: We found that: i) there is an asymmetric metabolic activation during motor execution and mirror task between hemispheres (with a predominance that is ipsilateral to the amputated limb), ii) increased metabolic response in the PMC ipsilateral to the amputation is associated with increased PLP (during both experimental tasks), while increased metabolic response in the contralateral PMC is associated with increased RLP (during the mirror motor task only); ii) increased metabolic activity of the ipsilateral premotor region is associated with increased PLP during the motor mirror task; iii) RLP was only associated with higher metabolic activity in the contralateral PMC and lower metabolic activity in the ipsilateral inferior frontal region during motor mirror task, but PLP was associated with higher metabolic activity during both tasks. CONCLUSION: These results suggest there is both task and region specificity for the association between the brain metabolic response and the two different types of post-amputation pain. The metabolic predominance that is ipsilateral to the amputated limb during both tasks was associated with higher levels of PLP, suggesting a cortical motor network activity imbalance due to potential interhemispheric compensatory mechanisms. The present work contributes to the understanding of the underlying topographical patterns in the motor-related circuits associated with pain after amputations.

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ABSTRACT Objective This study aimed at assessing the alterations in upper limb motor impairment and connectivity between motor areas following the post-stroke delivery of cathodal transcranial direct current stimulation sessions. Methods Modifications in the Fugl-Meyer Assessment scores, connectivity between the primary motor cortex of the unaffected and affected hemispheres, and between the primary motor and premotor cortices of the unaffected hemisphere were compared prior to and following six sessions of cathodal transcranial direct current stimulation application in 13 patients (active = 6; sham = 7); this modality targets the primary motor cortex of the unaffected hemisphere early after a stroke. Results Clinically relevant distinctions in Fugl-Meyer Assessment scores (≥9 points) were observed more frequently in the Sham Group than in the Active Group. Between-group differences in the alterations in Fugl-Meyer Assessment scores were not statistically significant (Mann-Whitney test, p=0.133). ROI-to-ROI correlations between the primary motor cortices of the affected and unaffected hemispheres post-therapeutically increased in 5/6 and 2/7 participants in the Active and Sham Groups, respectively. Between-group differences in modifications in connectivity between the aforementioned areas were not statistically significant. Motor performance enhancements were more frequent in the Sham Group compared to the Active Group. Conclusion The results of this hypothesis-generating investigation suggest that heightened connectivity may not translate into early clinical benefits following a stroke and will be crucial in designing larger cohort studies to explore mechanisms underlying the impacts of this intervention. ClinicalTrials.gov Identifier: NCT02455427.

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ABSTRACT. This is the case report of a woman who started to write and read from right to left after anterior cerebral artery stroke, affecting the left supplementary motor area. No cases were found in the literature with exactly the same characteristics. She has been able to read and write faster after rehabilitation approach at Sarah Network of Rehabilitation Hospitals, in the Belo Horizonte city unit, Brazil, despite the maintenance of the inversion. She returned to her previous activities in an adaptive way. It was discussed how the dysfunction in this cerebral area and its connections may disturb the reading strategy and direction.

RESUMO. Relato do caso de uma mulher que passou a escrever e ler da direita para a esquerda após um acidente vascular encefálico isquêmico de artéria cerebral anterior, acometendo área motora suplementar esquerda. Não foram encontrados casos na literatura exatamente com as mesmas características. Durante a participação da paciente no programa de reabilitação neurológica da Rede Sarah de Hospitais de Reabilitação, unidade Belo Horizonte, foram observados ganhos na agilidade de leitura e escrita, ainda que mantendo a inversão, e retorno às suas atividades de forma adaptada. Realizou-se discussão de como o comprometimento dessa área e de suas conexões pode perturbar a estratégia de leitura e sua direção.

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Transcranial Magnetic Stimulation (TMS) serves as a crucial tool in evaluating motor cortex excitability by applying short magnetic pulses to the skull, inducing neuron depolarization in the cerebral cortex through electromagnetic induction. This technique leads to the activation of specific skeletal muscles recorded as Motor-Evoked Potentials (MEPs) through electromyography. Although various methodologies assess cortical excitability with TMS, measuring MEP amplitudes offers a straightforward approach, especially when comparing excitability states pre- and post-interventions designed to alter cortical excitability. Despite TMS's widespread use, the absence of a standardized procedure for such measurements in existing literature hinders the comparison of results across different studies. This paper proposes a standardized procedure for assessing changes in motor cortical excitability using single-pulse TMS pre- and post-intervention. The recommended approach utilizes an intensity equating to half of the MEP's maximum amplitude, thereby ensuring equal likelihood of amplitude increase or decrease, providing a consistent basis for future studies and facilitating meaningful comparisons of results.•A method for assessing changes in motor cortical excitability using single-pulse TMS before and after a specified intervention.•We recommend using an intensity equal to half of the MEP's maximum amplitude during evaluations to objectively assess motor cortical excitability changes post-intervention.

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INTRODUCTION: Trigeminal neuropathic pain (TNP) is a syndrome of severe, disabling, constant facial pain arising from the trigeminal nerve or ganglion. Arteriovenous malformations (AVM) are a rare cause of TNP. The limited choices of intervention of TNP include peripheral nerve stimulation, trigeminal nucleotomy and motor cortex stimulation. CASE REPORT: We present a 56-year-old man who suffered from trigeminal neuropathic pain secondary to nerve compression due to a giant posterior fossa AVM. The pain was refractory to drug treatment. From all the therapeutic options available we declined the microvascular decompression of the trigeminal nerve due to the presence of the giant AVM, or stereotactic radiosurgery because of the AVM´s diffuse nidus. After a multidisciplinary discussion we proposed a minimally invasive, safe and reversible treatment: Motor Cortical Stimulation (MCS). We placed a 16-pole epidural electrode on the right precentral gyrus. The patient had satisfactory pain control with some supplemental medication. No complications or side effects such as seizures, sensory disturbances or infections were presented. DISCUSSION: The limited choices of intervention of TNP include peripheral nerve stimulation, trigeminal nucleotomy and MCS. Henssen et al performed a systematic review where they investigated the effectiveness of MCS and discovered that this is significantly different among different chronic neuropathic orofacial pain disorders. A visual analogue scale (VAS) measured median pain relief of 66.5% was found. CONCLUSION: MCS should be one more tool to consider in highly selected cases, when other treatments are unfeasible.

Introducción: El dolor neuropático trigeminal (DNT) es un síndrome de dolor facial intenso, incapacitante y constante que surge del nervio o ganglio del trigémino. Las malformaciones arteriovenosas (MAV) son una causa rara de DNT. Las opciones terapéuticas de DNT incluyen la estimulación de los nervios periféricos, la nucleotomía del trigémino y la estimulación cortical motora. Caso clínico: Presentamos el caso de un varón de 56 años con dolor neuropático trigeminal secundario a compresión nerviosa por una MAV gigante de fosa posterior. El dolor era refractario al tratamiento farmacológico. De todas las opciones terapéuticas disponibles, desestimamos la descompresión microvascular del nervio trigémino por la presencia de la MAV gigante, o la radiocirugía estereotáctica, por ser difuso el nido de la MAV. Tras una discusión multidisciplinar propusimos un tratamiento mínimamente invasivo, seguro y reversible: Estimulación cortical motora (ECM). Colocamos un electrodo epidural en el giro precentral derecho. El paciente tuvo un control satisfactorio del dolor con medicación suplementaria. No presentó complicaciones ni efectos secundarios como convulsiones, alteraciones sensoriales o infecciones. Discusión: Las opciones limitadas de intervención de DNT incluyen estimulación nerviosa periférica, nucleotomía trigeminal y ECM. Henssen et al realizaron una revisión sistemática donde investigaron la efectividad de MCS y descubrieron que esto es significativamente diferente entre los diferentes trastornos de dolor orofacial neuropático crónico. Se encontró un promedio de alivio del dolor medida por una escala analógica visual del 66,5%. Conclusión: La ECM debería ser una herramienta más a considerar en casos estrictamente seleccionados donde otros tratamientos no son viables.

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Epidural motor cortex stimulation (MCS) is an effective treatment for refractory neuropathic pain; however, some individuals are unresponsive. In this study, we correlated the effectiveness of MCS and refractoriness with the expression of cytokines, neurotrophins, and nociceptive mediators in the dorsal root ganglion (DRG), sciatic nerve, and plasma of rats with sciatic neuropathy. MCS inhibited hyperalgesia and allodynia in two-thirds of the animals (responsive group), and one-third did not respond (refractory group). Chronic constriction injury (CCI) increased IL-1ß in the nerve and DRG, inhibited IL-4, IL-10, and IL-17A in the nerve, decreased ß-endorphin, and enhanced substance P in the plasma, compared to the control. Responsive animals showed decreased NGF and increased IL-6 in the nerve, accompanied by restoration of local IL-10 and IL-17A and systemic ß-endorphin. Refractory animals showed increased TNF-α and decreased IFNγ in the nerve, along with decreased TNF-α and IL-17A in the DRG, maintaining low levels of systemic ß-endorphin. Our findings suggest that the effectiveness of MCS depends on local control of inflammatory and neurotrophic changes, accompanied by recovery of the opioidergic system observed in neuropathic conditions. So, understanding the refractoriness to MCS may guide an improvement in the efficacy of the technique, thus benefiting patients with persistent neuropathic pain.

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The ability to learn motor skills implicates an improvement in accuracy, speed and consistency of movements. Motor control is related to movement execution and involves corticospinal neurons (CSp), which are broadly distributed in layer 5B of the motor and somatosensory cortices. CSp neurons innervate the spinal cord and are functionally diverse. However, whether CSp activity differs between different cortical areas throughout motor learning has been poorly explored. Given the importance and interaction between primary motor (M1) and somatosensory (S1) cortices related to movement, we examined the functional roles of CSp neurons in both areas. We induced the expression of GCaMP7s calcium indicator to perform photometric calcium recordings from layer 5B CSp neurons simultaneously in M1 and S1 cortices and track their activity while adult mice learned and performed a cued lever-press task. We found that during early learning sessions, the population calcium activity of CSp neurons in both cortices during movement did not change significantly. In late learning sessions the peak amplitude and duration of calcium activity CSp neurons increased in both, M1 and S1 cortices. However, S1 and M1 CSp neurons display a different temporal dynamic during movements that occurred when animals learned the task; both M1 and S1 CSp neurons activate before movement initiation, however, M1 CSp neurons continue active during movement performance, reinforcing the idea of the diversity of the CSp system and suggesting that CSp neuron activity in M1 and S1 cortices throughout motor learning have different functional roles for sensorimotor integration.

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Introduction: The brain tumor is frequently related to severe motor impairment and impacts the quality of life. The corticospinal tract can sometimes be affected depending on the type and size of the neoplasm, so different tools can evaluate motor function and connections. It is essential to organize surgical procedures and plan the approach. Functional motor status is mapped before, during, and after surgery. Studying corticospinal tract status can help map the functional areas, predict postoperative outcomes, and help the decision, reducing neurological deficits, aiming to preserve functional networks, using the concepts of white matters localization and fibbers connections. Nowadays, there are new techniques that provide functional information regarding the motor cortex, such as transcranial magnetic stimulation (TMS), direct cortical stimulation (DCS), and navigated TMS (nTMS). These tools can be used to plan a customized surgical strategy and the role of motor evoked potentials (MEPs) is well described during intra-operative, using intraoperative neuromonitoring. MEPs can help to localize primary motor areas and delineate the cut-off point of resection in real-time, using direct stimulation. In the post-operative, the MEP has increased your function as a predictive marker of permanent or transitory neurological lesion marker. Methods: Systematic review performed in MEDLINE via PUBMED, EMBASE, and SCOPUS databases regarding the post-operative assessment of MEP in patients with brain tumors. The search strategy included the following terms: (("Evoked Potentials, Motor"[Mesh]) AND "Neoplasms"[Mesh]) AND "Transcranial Magnetic Stimulation"[Mesh] AND "Brain Tumor"[Mesh]), the analysis followed the PRISMA guidelines for systematic reviews, the review spanned until 06/04/2021, inclusion criteria were studies presenting confirmed diagnosis of brain tumor (primary or metastatic), patients >18 y/o, using TMS, Navigated TMS, and/or Evoked Potentials as tools in preoperative planning or at the intra-operative helping the evaluation of the neurological status of the motor cortex, articles published in peer-reviewed journals, and written in English or Portuguese. Results: A total of 38 studies were selected for this review, of which 14 investigated the potential of nTMS to predict the occurrence of motor deficits, while 25 of the articles investigated the capabilities of the nTMS technique in performing pre/intraoperative neuro mapping of the motor cortex. Conclusion: Further studies regarding motor function assessment are needed and standardized protocols for MEPs also need to be defined.

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ABSTRACT BACKGROUND AND OBJECTIVES: Fibromyalgia (FM) is a chronic widespread musculoskeletal pain resulting in central sensitization of nociceptive signaling. Transcranial direct current stimulation (tDCS) over the left motor cortex (M1) is a non-invasive neuromodulation technique indicated for a broad range of chronic pain disorders, including FM. Studies suggest that left and right M1 (contralateral and ipsilateral hemisphere of tDCS stimulation) are modulated. But it is necessary to clarify the differences in clinical pain perception comparing the right and left side of the body. This study aimed to evaluate the pain-related difference between right-left side of the body after five sessions of anodal tDCS in women with FM. METHODS: A double-blinded, parallel, randomized, sham-controlled trial with 30 women with FM was performed. Five sessions of anodal C3 and cathodal supraorbital (Fp2) tDCS were conducted (2 mA for 20 min). Pain, impact of FM and anxiety were evaluated. No statistically significant three-way interaction between time, stimulation type and body side were found. RESULTS: Active-tDCS showed significant improvement in pain, but impact of FM and anxiety did not show significant improvement. CONCLUSION: Five sessions of anodal tDCS over the left M1 improves pain in women with FM, however there was no difference between right-left body sides.

RESUMO JUSTIFICATIVA E OBJETIVOS: A fibromialgia (FM) é uma dor musculoesquelética crônica generalizada que resulta na sensibilização central da sinalização nociceptiva. A estimulação transcraniana de corrente contínua (eTCC) sobre o córtex motor esquerdo (M1) é uma técnica de neuromodulação não invasiva indicada para uma ampla gama de distúrbios de dor crônica, incluindo a FM. Estudos sugerem a modulação do M1 esquerdo e direito (hemisfério contralateral e ipsilateral da eTCC). Mas é necessário esclarecer as diferenças na percepção clínica da dor comparando os lados direito e esquerdo do corpo. Este estudo teve como objetivo avaliar a diferença relacionada à dor entre o lado direito e esquerdo do corpo após cinco sessões de eTCC anodal em mulheres com FM. MÉTODOS: Foi realizado um estudo duplo-cego, paralelo, randomizado e controlado por sham com 30 mulheres com FM. Foram realizadas cinco sessões de eTCC anodais C3 e supraorbitais catodais (Fp2) (2 mA por 20 min). Foram avaliados a dor, o impacto da FM e a ansiedade. Não foi encontrada nenhuma interação de três vias estatisticamente significativa entre tempo, tipo de estimulação e lado do corpo. RESULTADOS: A eTCC-Ativa mostrou uma melhora significativa na dor, mas o impacto da FM e da ansiedade não mostrou uma melhora significativa. CONCLUSÃO: Cinco sessões de eTCC anodal sobre o M1 esquerdo melhoram a dor nas mulheres com FM, entretanto não houve diferença entre os lados direito e esquerdo do corpo.

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Transcranial direct current stimulation (tDCS) has emerged as a promising intervention in clinical and behavioral neuroscience; however, the response variability to this technique has limited its impact, partly due to the widespread of current flow with conventional methods. Here, we investigate whether a more targeted, focal approach over the primary motor cortex (M1) is advantageous for motor learning and targeting specific neuronal populations. Our preliminary results show that focal stimulation leads to enhanced skill learning and differentially recruits distinct pathways to M1. This finding suggests that focal tDCS approaches may improve the outcomes of future studies aiming to enhance behavior.

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Patients with atrophy in motor brain regions exhibit selective deficits in processing action-related meanings, suggesting a link between movement conceptualization and the amount of regional tissue. Here we examine such a relation in a unique opposite model: a rare patient with a double cortex (due to subcortical band heterotopia) in primary/supplementary motor regions, and no double cortex in multimodal semantic regions. We measured behavioral performance in action- and object-concept processing as well and resting-state functional connectivity. Both dimensions involved comparisons with healthy controls. Results revealed preserved accuracy in action and object categories for the patient. However, unlike controls, the patient exhibited faster performance for action than object concepts, a difference that was uninfluenced by general cognitive abilities. Moreover, this pattern was accompanied by heightened functional connectivity between the bilateral primary motor cortices. This suggests that a functionally active double motor cortex may entail action-processing advantages. Our findings offer new constraints for models of action semantics and motor-region function at large.

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Introduction: Pyramidal tract neurons (PTNs) are fundamental elements for motor control. However, it is largely unknown if PTNs are segregated into different subtypes with distinct characteristics. Methods: Using anatomical and electrophysiological tools, we analyzed in mice motor cortex PTNs projecting to red and pontine midbrain nuclei, which are important hubs connecting cerebral cortex and cerebellum playing a critical role in the regulation of movement. Results: We reveal that the vast majority of M1 neurons projecting to the red and pontine nuclei constitutes different populations. Corticopontine neurons have higher conduction velocities and morphologically, a most homogeneous dendritic and spine distributions along cortical layers. Discussion: The results indicate that cortical neurons projecting to the red and pontine nuclei constitute distinct anatomical and functional pathways which may contribute differently to sensorimotor integration.

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Reaction time is accelerated if a loud (startling) sound accompanies the cue-the "StartReact" effect. Animal studies revealed a reticulospinal substrate for the startle reflex; StartReact may similarly involve the reticulospinal tract, but this is currently uncertain. Here we trained two female macaque monkeys to perform elbow flexion/extension movements following a visual cue. The cue was sometimes accompanied by a loud sound, generating a StartReact effect in electromyogram response latency, as seen in humans. Extracellular recordings were made from antidromically identified corticospinal neurons in primary motor cortex (M1), from the reticular formation (RF), and from the spinal cord (SC; C5-C8 segments). After loud sound, task-related activity was suppressed in M1 (latency, 70-200 ms after cue), but was initially enhanced (70-80 ms) and then suppressed (140-210 ms) in RF. SC activity was unchanged. In a computational model, we simulated a motoneuron pool receiving input from different proportions of the average M1 and RF activity recorded experimentally. Motoneuron firing generated simulated electromyogram, allowing reaction time measurements. Only if ≥60% of motoneuron drive came from RF (≤40% from M1) did loud sound shorten reaction time. The extent of shortening increased as more drive came from RF. If RF provided <60% of drive, loud sound lengthened the reaction time-the opposite of experimental findings. The majority of the drive for voluntary movements is thus likely to originate from the brainstem, not the cortex; changes in the magnitude of the StartReact effect can measure a shift in the relative importance of descending systems.SIGNIFICANCE STATEMENT Our results reveal that a loud sound has opposite effects on neural spiking in corticospinal cells from primary motor cortex, and in the reticular formation. We show that this fortuitously allows changes in reaction time produced by a loud sound to be used to assess the relative importance of reticulospinal versus corticospinal control of movement, validating previous noninvasive measurements in humans. Our findings suggest that the majority of the descending drive to motoneurons producing voluntary movement in primates comes from the reticulospinal tract, not the corticospinal tract.

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Objective.Brain-computer interface (BCI) is a tool that can be used to train brain self-regulation and influence specific activity patterns, including functional connectivity, through neurofeedback. The functional connectivity of the primary motor area (M1) and cerebellum play a critical role in motor recovery after a brain injury, such as stroke. The objective of this study was to determine the feasibility of achieving control of the functional connectivity between M1 and the cerebellum in healthy subjects. Additionally, we aimed to compare the brain self-regulation of two different feedback modalities and their effects on motor performance.Approach.Nine subjects were trained with a real-time functional magnetic resonance imaging BCI system. Two groups were conformed: equal feedback group (EFG), which received neurofeedback that weighted the contribution of both regions of interest (ROIs) equally, and weighted feedback group (WFG) that weighted each ROI differentially (30% cerebellum; 70% M1). The magnitude of the brain activity induced by self-regulation was evaluated with the blood-oxygen-level-dependent (BOLD) percent change (BPC). Functional connectivity was assessed using temporal correlations between the BOLD signal of both ROIs. A finger-tapping task was included to evaluate the effect of brain self-regulation on motor performance.Main results.A comparison between the feedback modalities showed that WFG achieved significantly higher BPC in M1 than EFG. The functional connectivity between ROIs during up-regulation in WFG was significantly higher than EFG. In general, both groups showed better tapping speed in the third session compared to the first. For WFG, there were significant correlations between functional connectivity and tapping speed.Significance.The results show that it is possible to train healthy individuals to control M1-cerebellum functional connectivity with rtfMRI-BCI. Besides, it is also possible to use a weighted feedback approach to facilitate a higher activity of one region over another.

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Motor cortex stimulation via surgically implanted electrodes has been used as an off-label treatment for chronic neuropathic pain, but its efficacy has not been fully established. We aimed to objectively study the efficacy of motor cortex stimulation and characterize potential predictors of response. In this randomized, double-blind, sham-controlled, single centre trial, we recruited 18 patients with chronic neuropathic pain who did not adequately respond to conventional treatment and had a numerical pain rating scale (NRS) score ≥6. Patients were initially assigned to receive 3 months of active ('on') or sham ('off') stimulation in a double-blind cross-over phase. This was followed by a 3-month single-blind phase, and 6 months of open-label follow-up. A meaningful response in our trial was defined as a ≥30% or 2-point reduction in NRS scores during active stimulation. Using Bayesian statistics, we found a 41.4% probability of response towards on versus off motor cortex stimulation. The probability of improvement during active stimulation (double-blind, single-blind and open-label phases) compared to baseline was 47.2-68.5%. Thirty nine per cent of the patients were considered long-term responders, 71.4% of whom had facial pain, phantom limb pain or complex regional pain syndrome. In contrast, 72.7% of non-responders had either post-stroke pain or pain associated with brachial plexus avulsion. Thirty-nine per cent of patients had a substantial postoperative analgesic effect after electrode insertion in the absence of stimulation. Individuals with diagnoses associated with a good postoperative outcome or those who developed an insertional effect had a near 100% probability of response to motor cortex stimulation. In summary, we found that ∼40% of patients responded to motor cortex stimulation, particularly those who developed an insertional effect or had specific clinical conditions that seemed to predict an appropriate postoperative response.

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The knowledge about how different subsystems participate and interplay in sensorimotor control is fundamental to understand motor deficits associated with CNS injury and movement recovery. The role of corticospinal (CS) and rubrospinal (RS) projections in motor control has been extensively studied and compared, and it is clear that both systems are important for skilled movement. However, during phylogeny, the emerging cerebral cortex took a higher hierarchical role controlling rubro-cerebellar circuits. Here, we present anatomical, neurophysiological, and behavioral evidence suggesting that both systems modulate complex segmental neuronal networks in a parallel way, which is important for sensorimotor integration at spinal cord level. We also highlight that, although specializations exist, both systems could be complementary and potentially subserve motor recovery associated with CNS damage.