Prefrontal-subthalamic theta signaling mediates delayed responses during conflict processing.

While medial frontal cortex (MFC) and subthalamic nucleus (STN) have been implicated in conflict monitoring and action inhibition, respectively, an integrated understanding of the spatiotemporal and spectral interaction of these nodes and how they interact with motor cortex (M1) to definitively modify motor behavior during conflict is lacking. We recorded neural signals intracranially across presupplementary motor area (preSMA), M1, STN, and globus pallidus internus (GPi), during a flanker task in 20 patients undergoing deep brain stimulation implantation surgery for Parkinson disease or dystonia. Conflict is associated with sequential and causal increases in local theta power from preSMA to STN to M1 with movement delays directly correlated with increased STN theta power, indicating preSMA is the MFC locus that monitors conflict and signals STN to implement a 'break.' Transmission of theta from STN-to-M1 subsequently results in a transient increase in M1-to-GPi beta flow immediately prior to movement, modulating the motor network to actuate the conflict-related action inhibition (i.e., delayed response). Action regulation during conflict relies on two distinct circuits, the conflict-related theta and movement-related beta networks, that are separated spatially, spectrally, and temporally, but which interact dynamically to mediate motor performance, highlighting complex parallel yet interacting networks regulating movement.

Impact of multiple-session home-based transcranial direct current stimulation (M-HB-tDCS) on eating behavior in fibromyalgia: A factorial randomized clinical trial.

BACKGROUND: Multiple-session home-based self-applied transcranial direct current stimulation (M-HB-self-applied-tDCS) has previously been found to effectively reduce chronic pain and enhance cognitive function. However, the effectiveness of this method for disordered eating behavior still needs to be studied. OBJECTIVE: This study aimed to assess whether 20 sessions of M-HB-self-applied-tDCS, administered over four weeks to either the left dorsolateral prefrontal cortex (L-DLPFC) or primary motor cortex (M1), could improve various aspects of eating behavior, anthropometric measures, and adherence. METHODS: We randomly assigned 102 fibromyalgia patients between the ages of 30 and 65 to one of four tDCS groups: L-DLPFC (anodal-(a)-tDCS, n = 34; sham-(s)-tDCS, n = 17) or M1 (a-tDCS, n = 34; s-tDCS, n = 17). Patients self-administered 20-min tDCS sessions daily with 2 mA under remote supervision following in-person training. RESULTS: Generalized linear models revealed significant effects of M-HB-self-applied-tDCS compared to s-tDCS on uncontrolled eating (UE) (Wald χ2 = 5.62; df = 1; P = 0.018; effect size, ES = 0.55), and food craving (Wald χ2 = 5.62; df = 1; P = 0.018; ES = 0.57). Regarding fibromyalgia symptoms, we found a differentiated impact of a-tDCS on M1 compared to DLPFC in reducing food cravings. Additionally, M-HB-a-tDCS significantly reduced emotional eating and waist size. In contrast, M1 stimulation was more effective in improving fibromyalgia symptoms. The global adherence rate was high, at 88.94%. CONCLUSION: These findings demonstrate that M-HB-self-applied-tDCS is a suitable approach for reducing uncontrolled and emotional eating, with greater efficacy in L-DLPFC. Furthermore, these results revealed the influence of fibromyalgia symptoms on M-HB-self-applied-tDCS's, with M1 being particularly effective in mitigating food cravings and reducing fibromyalgia symptoms.

Cortical stimulation depth of nTMS investigated in a cohort of convexity meningiomas above the primary motor cortex.

BACKGROUND: In clinical routine, navigated transcranial magnetic stimulation (nTMS) is usually applied down to 25 mm. Yet, besides clinical experience and mathematical models, the penetration depth remains unclear. This study aims to investigate the maximum cortical stimulation depth of nTMS in patients with meningioma above the primary motor cortex, causing a displacement of the primary motor cortex away from the skull. NEW METHOD: nTMS stimulation data was reviewed regarding the maximum depth of stimulations eliciting motor-evoked potentials (MEPs). Additionally, electric field values and stimulation intensity were analyzed. RESULTS: Out of a consecutive cohort of 17 meningioma cases, 3 cases of meningioma located in motor-eloquent regions of the upper extremity and 3 cases of the lower extremity were analyzed after fulfilling all inclusion criteria. Regarding the upper extremity motor representations, the MEP could be elicited at a stimulation depth of up to 44 mm, with an electric field of 69 V/m. These results were found in 1 case with the maximum potential distance to the cortex being higher than the maximum stimulation depth eliciting MEPs. For the lower extremities, a maximum depth of 40 mm was recorded (electric field 64 V/m). COMPARISON WITH EXISTING METHODS: None available CONCLUSIONS: The effect of nTMS is not limited to superficial cortical stimulation alone. Depending on electric-field intensity and focality, nTMS stimulation can be applied at a depth of 44 mm. In all cases, electric field strength was comparable and no superficial cortex with comparable electric field strength was observed to elicit MEPs.

Navigated transcranial magnetic stimulation to measure motor evoked potentials in a child with hemispheric polymicrogyria and focal epilepsy.

Malformations of cortical development such as polymicrogyria can cause medically refractory epilepsy. Epilepsy surgery (hemispherotomy) can be a good treatment option. In recent years, navigated transcranial magnetic stimulation (nTMS), a noninvasive brain mapping technique, has been used to localize the eloquent cortex for presurgical evaluation of patients with epilepsy. In the present case study, neurophysiological markers of the primary motor cortex (M1), including resting motor threshold (rMT), motor evoked potentials (MEPs), and silent period (SP), were assessed in both hands of a right-handed 10-year-old girl with a history of epilepsy and right hemispheric polymicrogyria. Bilateral MEPs with short latencies were elicited from the contralesional side. The average MEP amplitude and the latency for the patient's paretic and non-paretic hands differed significantly. We conclude that nTMS is a safe and tolerable procedure that can be used for presurgical evaluation in children with intractable epilepsy.

Positioning of epidural electrode for motor cortex stimulation in general anesthesia based on intraoperative electrophysiological monitoring to treat refractory trigeminal neuropathic pain.

BACKGROUND: Motor cortex stimulation (MCS) represents a treatment option for refractory trigeminal neuralgia (TGN). Usually, patients need to be awake during surgery to confirm a correct position of the epidural electrode above the motor cortex, reducing patient's comfort. METHOD: Epidural cortical mapping (ECM) and motor evoked potentials (MEPs) were intraoperatively performed for correct localization of motor cortex under general anesthesia that provided comparable results to test stimulation after letting the patient to be awake during the operation. CONCLUSION: Intraoperative ECM and MEPs facilitate a confirmation of correct MCS-electrode position above the motor cortex allowing the MCS-procedure to be performed under general anesthesia.

Approach-avoidance behavior and motor-specific modulation towards smoking-related cues in smokers.

AIMS: By performing three transcranial magnetic stimulation (TMS) experiments, we measured the motor-specific modulatory mechanisms in the primary motor cortex (M1) at both the intercortical and intracortical levels when smokers actively approach or avoid smoking-related cues. DESIGN, SETTING AND PARTICIPANTS: For all experiments, the design was group (smokers versus non-smokers) × action (approach versus avoidance) × image type (neutral versus smoking-related). The study was conducted at the Shanghai University of Sport, CHN, TMS Laboratory. For experiment 1, 30 non-smokers and 30 smokers; for experiment 2, 16 non-smokers and 16 smokers; for experiment 3, 16 non-smokers and 16 smokers. MEASUREMENTS: For all experiments, the reaction times were measured using the smoking stimulus-response compatibility task. While performing the task, single-pulse TMS was applied to the M1 in experiment 1 to measure the excitability of the corticospinal pathways, and paired-pulse TMS was applied to the M1 in experiments 2 and 3 to measure the activity of intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI) circuits, respectively. FINDINGS: Smokers had faster responses when approaching smoking-related cues (F1,58 = 36.660, P < 0.001, η p 2 = 0.387), accompanied by higher excitability of the corticospinal pathways (F1,58 = 10.980, P = 0.002, η p 2 = 0.159) and ICF circuits (F1,30 = 22.187, P < 0.001, η p 2 = 0.425), while stronger SICI effects were observed when they avoided these cues (F1,30 = 10.672, P = 0.003, η p 2 = 0.262). CONCLUSIONS: Smokers appear to have shorter reaction times, higher motor-evoked potentials and stronger intracortical facilitation effects when performing approach responses to smoking-related cues and longer reaction times, a lower primary motor cortex descending pathway excitability and a stronger short-interval intracortical inhibition effect when avoiding them.

Emergence of preparatory dynamics in VIP interneurons during motor learning.

To determine what actions to perform in each context, animals must learn how to execute motor programs in response to sensory cues. In rodents, the interface between sensory processing and motor planning occurs in the secondary motor cortex (M2). Here, we investigate dynamics in vasointestinal peptide (VIP) and somatostatin (SST) interneurons in M2 during acquisition of a cue-based, reach-to-grasp (RTG) task in mice. We observe the emergence of preparatory activity consisting of sensory responses and ramping activation in a subset of VIP interneurons during motor learning. We show that preparatory and movement activities in VIP neurons exhibit compartmentalized dynamics, with principal component 1 (PC1) and PC2 reflecting primarily movement and preparatory activity, respectively. In contrast, we observe later and more synchronous activation of SST neurons during the movement epoch with learning. Our results reveal how VIP population dynamics might support sensorimotor learning and compartmentalization of sensory processing and movement execution.

Atypical Activation of Laryngeal Somatosensory-Motor Cortex During Vocalization in People With Unexplained Chronic Cough.

Importance: Unexplained chronic cough is common and has substantial negative quality-of-life implications, yet its causes are not well understood. A better understanding of how peripheral and central neural processes contribute to chronic cough is essential for treatment design. Objective: To determine if people with chronic cough exhibit signs of abnormal neural processing over laryngeal sensorimotor cortex during voluntary laryngeal motor activity such as vocalization. Design, Setting, and Participants: This was a cross-sectional study of a convenience sample of participants with chronic cough and healthy participants. Testing was performed in an acoustically and electromagnetically shielded chamber. In a single visit, electroencephalographic (EEG) signals were recorded from participants with chronic cough and healthy participants during voice production. The chronic cough group participants presented with unexplained cough of 8 weeks or longer duration with prior medical evaluation including negative results of chest imaging. None of the participants had a history of any neurologic disease known to impair vocalization or swallowing. Data collection for the healthy control group occurred from February 2 to June 28, 2018, and for the chronic cough group, from November 22, 2021, to June 21, 2022. Data analysis was performed from May 1 to October 30, 2022. Exposure: Participants with or without chronic cough. Main Outcome Measures: Event-related spectral perturbation over the laryngeal area of somatosensory-motor cortex from 0 to 30 Hz (ie, θ, α, and ß bands) and event-related coherence as a measure of synchronous activity between somatosensory and motor cortical regions. Results: The chronic cough group comprised 13 participants with chronic cough (mean [SD] age, 63.5 [7.8] years; 9 women and 4 men) and the control group, 10 healthy age-matched individuals (mean [SD] age, 60.3 [13.9] years; 6 women and 4 men). In the chronic cough group, the typical movement-related desynchronization over somatosensory-motor cortex during vocalization was significantly reduced across θ, α, and ß frequency bands when compared with the control group. Conclusions and Relevance: This cross-sectional study found that the typical movement-related suppression of brain oscillatory activity during vocalization is weak or absent in people with chronic cough. Thus, chronic cough affects sensorimotor cortical activity during the asymptomatic voluntary activation of laryngeal muscles.

Parietal/premotor lesions effects on visuomotor cognition in neuro-oncology patients: A multimodal study.

BACKGROUND: Assessing prior to surgery the functionality of brain areas exposed near the tumor requires a multimodal approach that combines the use of neuropsychological testing and fMRI tasks. Paradigms based on motor imagery, which corresponds to the ability to mentally evoke a movement, in the absence of actual action execution, can be used to test sensorimotor areas and the functionality of mental motor representations. METHODS: The most commonly used paradigm is the Limb Laterality Recognition Task (LLRT), requiring judgments about whether a limb belongs to the left or right side of the body. The group studied included 38 patients with high-grade (N = 21), low-grade (N = 11) gliomas and meningiomas (N = 6) in areas anterior (N = 21) and posterior (N = 17) to the central sulcus. Patients before surgery underwent neuropsychological assessment and fMRI. They performed the LLRT as an fMRI task. Accuracy, and neuroimaging data were collected and combined in a multimodal study. Structural MRI data analyses were performed by subtracting the overlap of volumes of interest (VOIs) plotted on lesions from the impaired patient group vs the overlap of VOIs from the spared group. The fMRI analyses were performed comparing the impaired patients and spared group. RESULTS: In general, patients were within normal limits on many neuropsychological screening tests. Compared with the control group, 17/38 patients had significantly different performance. The subtraction between the VOIs overlay of the impaired patients' group vs. the VOIs overlay of the spared group revealed that the areas maximally involved by lesions in the impaired patients' group were the right postcentral gyrus, right inferior parietal lobe, right supramarginal gyrus, right precentral gyrus, paracentral lobule, left postcentral gyrus, right superior parietal lobe, left inferior parietal lobe, and left superior and middle frontal gyrus. Analysis of the fMRI data showed which of these areas contributes to a correct LLRT performance. The task (vs. rest) in the group comparison (spared vs. impaired patients) activated a cluster in the left inferior parietal lobe. CONCLUSION: Underlying the altered performance at LLRT in patients with lesions to the parietal and premotor areas of the right and left hemispheres is a difference in activation of the left inferior parietal lobe. This region is involved in visuomotor processes and those related to motor attention, movement selection, and motor planning.

Smoking status ameliorates cholinergic impairments in cortical inhibition in patients with schizophrenia.

RATIONALE: Modulation of cortical excitability, in particular inhibition, is impaired in patients with schizophrenia. Chronic nicotine consumption, which is prevalent in this group, has been shown to alter cortical excitability in healthy individuals and to increase inhibitory activity. Thus, beneficial effects of smoking on impaired cortical excitability in patients with schizophrenia have been proposed, though direct experimental evidence is still lacking. OBJECTIVES: We aimed to explore the effect of chronic smoking on cortical excitability by comparing smoking and non-smoking patients with schizophrenia. METHOD: Twenty-six smoking and 19 non-smoking patients diagnosed with schizophrenia were included. Transcranial magnetic stimulation (TMS) applied to the primary motor cortex served as experimental paradigm for measuring corticospinal and intracortical excitability as follows: Resting motor threshold (RMT) and the input/output curve (I/O curve) were obtained to assess corticospinal excitability. Intracortical excitability was explored using paired-pulse TMS techniques (intracortical facilitation (ICF), short-latency intracortical inhibition (SICI) and short-latency afferent inhibition (SAI)). RESULTS: A significantly stronger inhibition in the cholinergically driven SAI protocol was observed in smokers compared to non-smokers. All other measures did not show significant differences between groups. CONCLUSION: Our results suggest an increased inhibition within cholinergic circuits due to chronic nicotine consumption in schizophrenia. This increase may compensate impaired cholinergic neurotransmission and could explain the high rate of smokers in schizophrenia.

TRPV1-mediated sonogenetic neuromodulation of motor cortex in freely moving mice.

Background.Noninvasive and cell-type-specific neuromodulation tools are critically needed for probing intact brain function. Sonogenetics for noninvasive activation of neurons engineered to express thermosensitive transient receptor potential vanilloid 1 (TRPV1) by transcranial focused ultrasound (FUS) was recently developed to address this need. However, using TRPV1-mediated sonogenetics to evoke behavior by targeting the cortex is challenged by its proximity to the skull due to high skull absorption of ultrasound and increased risks of thermal-induced tissue damage.Objective.This study evaluated the feasibility and safety of TRPV1-mediated sonogenetics in targeting the motor cortex to modulate the locomotor behavior of freely moving mice.Approach.Adeno-associated viral vectors was delivered to the mouse motor cortex via intracranial injection to express TRPV1 in excitatory neurons. A wearable FUS device was installed on the mouse head after a month to control neuronal activity by activating virally expressed TRPV1 through FUS sonication at different acoustic pressures. Immunohistochemistry staining ofex vivobrain slices was performed to verify neuron activation and evaluate safety.Results.TRPV1-mediated sonogenetic stimulation at 0.7 MPa successfully evoked rotational behavior in the direction contralateral to the stimulation site, activated cortical neurons as indicated by the upregulation of c-Fos, and did not induce significant changes in inflammatory or apoptotic markers (GFAP, Iba1, and Caspase-3). Sonogenetic stimulation of TRPV1 mice at a higher acoustic pressure, 1.1 MPa, induced significant changes in motor behavior and upregulation of c-Fos compared with FUS sonication of naïve mice at 1.1 MPa. However, signs of damage at the meninges were observed at 1.1 MPa.Significance.TRPV1-mediated sonogenetics can achieve effective and safe neuromodulation at the cortex with carefully selected FUS parameters. These findings expand the application of this technique to include superficial brain targets.

Effects of Anodal Transcranial Direct Current Stimulation on the Primary Motor Cortex in Women With Fibromyalgia: A Randomized, Triple-Blind Clinical Trial.

OBJECTIVES: The aim of this study was to analyze the effects of ten sessions of active transcranial direct current stimulation transcranial direct current stimulation (tDCS) (2 mA) with 13:20:13 stimulation at M1 in women with fibromyalgia (FM). To the best of our knowledge, this is the first article that uses this protocol in patients with FM. The main hypothesis is that the protocol would be effective in decreasing pain and that the results would last for up to 90 days. MATERIALS AND METHODS: This study was a randomized clinical trial with 35 women with FM divided into two groups, active tDCS group and sham tDCS group. A conventional tDCS device was used to deliver 2 mA for 13 minutes, with a 20-minute break followed by a further 13 minutes of stimulation for ten sessions. The anodal stimulus was in the left primary motor cortex M1 region. The primary outcome was a change in the visual analog scale and the Survey of Pain Attitudes pain score at the end of treatment, after 30 days, and 90 days after the end of treatment. Secondary outcomes included changes in the Fibromyalgia Impact Questionnaire, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, World Health Organization's Quality of Life Questionnaire, and Fatigue Assessment Scale. The Research Ethics Committee of the Centro Universitário da Grande Dourados under registration number Certificado de Apresentação de Apreciação Ética approved this research: 36444920.5.0000.5159. The study was registered in The Brazilian Registry of Clinical Trials with the identifier RBR-8wc8rjq. RESULTS: The active tDCS group showed improvement in pain after ten sessions (p < 0.001), after 30 days (p < 0.01), and after 90 days (p < 0.001) compared with sham tDCS. In addition, improvement in quality of life (QoL) and fatigue was observed in the active tDCS group. CONCLUSION: The results of this study suggest that active tDCS with an intensity of 2 mA for ten sessions was effective in decreasing pain and fatigue and improving QoL in patients with FM.

Reliability of active robotic neuro-navigated transcranial magnetic stimulation motor maps.

Transcranial magnetic stimulation (TMS) motor mapping is a safe, non-invasive method used to study corticomotor organization and intervention-induced plasticity. Reliability of resting maps is well established, but understudied for active maps and unestablished for active maps obtained using robotic TMS techniques. The objective of  this study was to determine the reliability of robotic neuro-navigated TMS motor map measures during active muscle contraction. We hypothesized that map area and volume would show excellent short- and medium-term reliability. Twenty healthy adults were tested on 3 days. Active maps of the first dorsal interosseous muscle were created using a 12 × 12 grid (7 mm spacing). Short- (24 h) and medium-term (3-5 weeks) relative (intra-class correlation coefficient) and absolute (minimal detectable change (MDC); standard error of measure) reliabilities were evaluated for map area, volume, center of gravity (CoG), and hotspot magnitude (peak-to-peak MEP amplitude at the hotspot), along with active motor threshold (AMT) and maximum voluntary contraction (MVC). This study found that AMT and MVC had good-to-excellent short- and medium-term reliability. Map CoG (x and y) were the most reliable map measures across sessions with excellent short- and medium-term reliability (p < 0.001). Map area, hotspot magnitude, and map volume followed with better reliability medium-term than short-term, with a change of 28%, 62%, and 78% needed to detect a true medium-term change, respectively. Therefore, robot-guided neuro-navigated TMS active mapping is relatively reliable but varies across measures. This, and MDC, should be considered in interventional study designs.

Exploring the interplay between mechanisms of neuroplasticity and cardiovascular health in aging adults: A multiple linear regression analysis study.

BACKGROUND: Neuroplasticity and cardiovascular health behavior are critically important factors for optimal brain health. OBJECTIVE: To assess the association between the efficacy of the mechanisms of neuroplasticity and metrics of cardiovascular heath in sedentary aging adults. METHODS: We included thirty sedentary individuals (age = 60.6 ± 3.8 y; 63 % female). All underwent assessments of neuroplasticity, measured by the change in amplitude of motor evoked potentials elicited by single-pulse Transcranial Magnetic Stimulation (TMS) at baseline and following intermittent Theta-Burst (iTBS) at regular intervals. Cardiovascular health measures were derived from the Incremental Shuttle Walking Test and included Heart Rate Recovery (HRR) at 1-min/2-min after test cessation. We also collected plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and c-reactive protein. RESULTS: We revealed moderate but significant relationships between TMS-iTBS neuroplasticity, and the predictors of cardiovascular health (|r| = 0.38 to 0.53, p < .05). HRR1 was the best predictor of neuroplasticity (ß = 0.019, p = .002). The best fit model (Likelihood ratio = 5.83, p = .016) of the association between neuroplasticity and HRR1 (ß = 0.043, p = .002) was selected when controlling for demographics and health status. VEGF and BDNF plasma levels augmented the association between neuroplasticity and HRR1. CONCLUSIONS: Our findings build on existing data demonstrating that TMS may provide insight into neuroplasticity and the role cardiovascular health have on its mechanisms. These implications serve as theoretical framework for future longitudinal and interventional studies aiming to improve cardiovascular and brain health. HRR1 is a potential prognostic measure of cardiovascular health and a surrogate marker of brain health in aging adults.

Features of the Sensorimotor Cortex Altered after Tooth Loss and Subsequent Implant Placement in the Maxilla of Rats.

OBJECTIVE: To investigate the synergistic changes of the astrocytes and neurons in the sensorimotor cortex during the process of implant osseointegration after insertion. METHODS: A total of 75 rats were allocated into three groups (n = 25): non-operated, extraction and implant. The rats in the latter two groups underwent extraction surgery of three maxillary right molars. One month later, the implant group received one titanium implant in the healed extraction socket. The rats were sacrificed on days 1, 3, 7, 14 and 28 after implantation. The brain sections, including sensory centre S1 and motor centre M1, were selected for further immunofluorescence for measurement of the synergistic morphological and quantitative changes of astrocytes and neurons. RESULTS: In layer IV of S1, the number of astrocytes in the implant group showed a descending trend with time; on days 1, 3, 7 and 14, the number of astrocytes in both the extraction group and the implant group was significantly higher than that in the non-operated group, and there was no difference between the extraction group and the implant group; however, on day 28, the number of astrocytes in the implant group was significantly lower than that in the extraction group. In layer V of M1, on days 7, 14 and 28, the number of astrocytes in the implant group was significantly lower than that in the extraction group; on days 14 and 28, the number of astrocytes in the extraction group was significantly higher than that in the non-operated group. In layer IV of S1 or layer V of M1, the number of neurons showed no significant changes between the three groups. CONCLUSION: The astrocytes in the face sensorimotor cortex were activated as a reaction to oral environment changes. This kind of neuroplasticity can be reversed by oral rehabilitation with dental implants. The motor cortex may be intimately related to osseointegration and osseoperception.

First Human In Vivo Neuroelectrophysiology Recordings of Uncrossed Dentatothalamocortical White-Matter Connections: On the Fast Tract.

OBJECTIVES: We aim to demonstrate intraoperative recording of cerebellar to cortical pathways that have not been previously recorded in humans, though imaged. METHODS: We report 2 cases with intraoperative neurophysiologic mapping of cerebellocortical tracts. Direct electrical stimulation of subcortical cerebellum along with recordings of cortical evoked potential and motor muscle recordings was performed during surgery. MR tractography data from healthy participants were used to further illustrate the pathways. RESULTS: Neurophysiologic recordings showed large waveforms of evoked potentials in bilateral electrodes over premotor/motor cortices on stimulation of the dentate nucleus. EMG recordings showed responses in face and neck muscles on stimulation of the dentate nucleus at the motor threshold. We thus demonstrated first-in-human in vivo neurophysiologic evidence of cerebellum to cortex responses through an uncrossed dentatothalamocortical tract to the motor/premotor cortices. DISCUSSION: This technique provides a methodology for the direct mapping of the cerebellum and cerebello-cerebral connections. We hypothesize a direct structural connection from the dentate nucleus to the premotor and motor cortices, as well as to ipsilateral hemibody muscles, acting as a fast route of cerebellar output and back up for immediate motor responses. This will further help explain the modulatory effects of the cerebellum on motor, language, and cognitive functions.

Active versus resting neuro-navigated robotic transcranial magnetic stimulation motor mapping.

Transcranial magnetic stimulation (TMS) motor mapping is a safe, non-invasive method that can be used to study corticomotor organization. Motor maps are typically acquired at rest, and comparisons to maps obtained during muscle activation have been both limited and contradictory. Understanding the relationship between functional activation of the corticomotor system as recorded by motor mapping is crucial for their use clinically and in research. The present study utilized robotic TMS paired with personalized neuro-navigation to examine the relationship between resting and active motor map measures and their relationship with motor performance. Twenty healthy right-handed participants underwent resting and active robotic TMS motor mapping of the first dorsal interosseous to 10% maximum voluntary contraction. Motor map parameters including map area, volume, and measures of map centrality were compared between techniques using paired sample tests of difference and Bland-Altman plots and analysis. Map area, volume, and hotspot magnitude were larger in the active motor maps, while map center of gravity and hotspot locations remained consistent between both maps. No associations were observed between motor maps and motor performance as measured by the Purdue Pegboard Test. Our findings support previous suggestions that maps scale with muscle contraction. Differences in mapping outcomes suggest rest and active motor maps may reflect functionally different corticomotor representations. Advanced analysis methods may better characterize the underlying neurophysiology of both types of motor mapping.

Hyper-connectivity between the left motor cortex and prefrontal cortex is associated with the severity of dysfunction of the descending pain modulatory system in fibromyalgia.

INTRODUCTION: The association between descending pain modulatory system (DPMS) dysfunction and fibromyalgia has been previously described, but more studies are required on its relationship with aberrant functional connectivity (FC) between the motor and prefrontal cortices. OBJECTIVES: The objective of this cross-sectional observational study was to compare the intra- and interhemispheric FC between the bilateral motor and prefrontal cortices in women with fibromyalgia, comparing responders and nonresponders to the conditioned pain modulation (CPM) test. METHODS: A cross-sectional sample of 37 women (23 responders and 14 nonresponders to the CPM test) with fibromyalgia diagnosed according to the American College of Rheumatology criteria underwent a standardized clinical assessment and an FC analysis using functional near-infrared spectroscopy. DPMS function was inferred through responses to the CPM test, which were induced by hand immersion in cold water (0-1°C). A multivariate analysis of covariance for main effects between responders and nonresponders was conducted using the diagnosis of multiple psychiatric disorders and the use of opioid and nonopioid analgesics as covariates. In addition, we analyzed the interaction between the CPM test response and the presence of multiple psychiatric diagnoses. RESULTS: Nonresponders showed increased FC between the left motor cortex (lMC) and the left prefrontal cortex (lPFC) (t = -2.476, p = 0.01) and right prefrontal cortex (rPFC) (t = -2.363, p = 0.02), even when both were considered as covariates in the regression analysis (lMC-lPFC: ß = -0.127, t = -2.425, p = 0.021; lMC-rPFC: ß = -0.122, t = -2.222, p = 0.033). Regarding main effects, a significant difference was only observed for lMC-lPFC (p = 0.035). A significant interaction was observed between the psychiatric disorders and nonresponse to the CPM test in lMC-lPFC (ß = -0.222, t = -2.275, p = 0.03) and lMC-rPFC (ß = -0.211, t = -2.2, p = 0.035). Additionally, a significant interaction was observed between the CPM test and FC in these two region-of-interest combinations, despite the psychiatric diagnoses (lMC-lPFC: ß = -0.516, t = -2.447, p = 0.02; lMC-rPFC: ß = -0.582, t = -2.805, p = 0.008). CONCLUSIONS: Higher FC between the lMC and the bilateral PFC may be a neural marker of DPMS dysfunction in women with fibromyalgia, although its interplay with psychiatric diagnoses also seems to influence this association.

Robotic mapping of motor cortex in children with perinatal stroke and hemiparesis.

Brain stimulation combined with intensive therapy may improve hand function in children with perinatal stroke-induced unilateral cerebral palsy (UCP). However, response to therapy varies and underlying neuroplasticity mechanisms remain unclear. Here, we aimed to characterize robotic motor mapping outcomes in children with UCP. Twenty-nine children with perinatal stroke and UCP (median age 11 ± 2 years) were compared to 24 typically developing controls (TDC). Robotic, neuronavigated transcranial magnetic stimulation was employed to define bilateral motor maps including area, volume, and peak motor evoked potential (MEP). Map outcomes were compared to the primary clinical outcome of the Jebsen-Taylor Test of Hand Function (JTT). Maps were reliably obtained in the contralesional motor cortex (24/29) but challenging in the lesioned hemisphere (5/29). Within the contralesional M1 of participants with UCP, area and peak MEP amplitude of the unaffected map were larger than the affected map. When comparing bilateral maps within the contralesional M1 in children with UCP to that of TDC, only peak MEP amplitudes were different, being smaller for the affected hand as compared to TDC. We observed correlations between the unaffected map when stimulating the contralesional M1 and function of the unaffected hand. Robotic motor mapping can characterize motor cortex neurophysiology in children with perinatal stroke. Map area and peak MEP amplitude may represent discrete biomarkers of developmental plasticity in the contralesional M1. Correlations between map metrics and hand function suggest clinical relevance and utility in studies of interventional plasticity.

Commissural Inter-M1 Cortico-cortical Evoked Potential: A Proof of Concept Report.

BACKGROUND: Intraoperative neuromonitoring of motor functions experienced a dramatical revolution in the last years thanks to significant advances in anesthesiology procedures and both preoperative and intraoperative mapping techniques. Asleep, awake, and combined intraoperative mapping techniques were responsible for an improvement in the functional outcomes in neurosurgery, providing reliable and reproducible mapping of both projection and association fibers involved in motor control. METHODS: We report inter-M1 cortico-cortical evoked potential (CCEP) recording during asleep resection of a bilateral parasagittal meningioma with intraoperative neuromonitoring and motor mapping. RESULTS: CCEPs were recorded between both M1 cortices with bipolar stimulations of both supplementary motor areas (10.5-11.5 µV). CONCLUSIONS: Here, we provide evidence of intraoperative mapping of commissural fibres involved in motor control in a patient with asleep technique as well as a review of the potential tracts involved in the connectivity underlying the motor function.