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Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain condition creating a wide range of urologic and pain symptoms. There is currently limited evidence to understand the mechanisms of IC/BPS. There have been recent studies suggesting that altered function in brain motor areas, particularly the supplementary motor cortex (SMA), relates to altered bladder sensorimotor control and may play an important role in IC/BPS. This study aims to provide evidence that non-invasive stimulation targeting the motor cortex may help reduce IC/BPS pain, as well as better understand the neural mechanism by which this stimulation targets neuromuscular dysfunction. This study is a two-group quadruple-blinded randomized controlled trial (RCT) of active vs. sham repetitive transmagnetic stimulation (rTMS). In addition, our study will also include functional magnetic resonance imaging (fMRI), pelvic floor electromyography (EMG), pelvic exam, and outcome measures and questionnaires to further study outcomes. Ethics and dissemination: All aspects of the study were approved by the Institutional Review Board of the University of Southern California (protocol HS-20–01021). All participants provided informed consent by the research coordinator/assistants. The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences. Trial registration: ClinicalTrials.gov NCT04734847. Registered on February 1, 2021. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to comprehensively investigate the functional connectivity of ten sub-regions within the premotor and supplementary motor areas (Right and Left Premotor 6d1, 6d2, 6d3, and Right and Left pre-Supplementary Motor (presma) and SMA). Using advanced magnetic resonance imaging (MRI), the objective was to understand the neurophysiological integrative characteristics of these regions by examining their connectivity with eight distinct functional brain networks. While previous studies have largely treated these areas as homogeneous entities, there is a significant gap in our understanding of the specific roles and connectivity profiles of their distinct sub-regions. The goal was to uncover the roles of these regions beyond conventional motor functions, contributing to a more holistic understanding of brain functioning. Methods: The study involved 198 healthy volunteers, with the primary methodology being functional connectivity analysis using advanced MRI techniques. Ten sub-regions within the premotor and supplementary motor areas served as seed regions, and their connectivity with eight distinct brain regional functional networks, including the Sensorimotor, Dorsal Attention, Language, Frontoparietal, Default Mode, Cerebellar, Visual, and Salience networks, was investigated. This approach allowed for the exploration of synchronized activity between these critical brain areas, shedding light on their integrated functioning and relationships with other brain networks. Results: The study revealed a nuanced landscape of functional connectivity for the premotor and supplementary motor areas with the main functional brain networks. Despite their high functional connectedness within the motor network, these regions displayed diverse functional integrations with other networks. There was moderate connectivity with the Sensorimotor and Dorsal Attention networks, highlighting their roles in motor execution and attentional processes. However, connectivity with the Language, Frontoparietal, Default Mode, Cerebellar, Visual, and Salience networks was generally low, indicating a primary focus on motor-related tasks. Conclusions: This study emphasized the multifaceted roles of the sub-regions of the premotor and supplementary motor areas. Beyond their crucial involvement in motor functions, these regions exhibited varied functional integrations with different brain networks. The observed disparities, especially in the Sensorimotor and Dorsal Attention networks, indicated a nuanced and specialized involvement of these regions in diverse cognitive functions. By delineating the specific connectivity profiles of these sub-regions, this study addresses the existing knowledge gap and suggests unique and distinct roles for each brain area in sophisticated cognitive tasks beyond their conventional motor functions. The results suggested unique and distinct roles for each brain area in sophisticated cognitive tasks beyond their conventional motor functions. This study underscores the importance of considering the broader neurophysiological landscape to comprehend the intricate roles of these brain areas, contributing to ongoing efforts in unravelling the complexities of brain function. [ABSTRACT FROM AUTHOR]

• Patients with post-COVID fatigue show reduced TMS-induced beta oscillations in SMA. • In patients, TMS-induced beta oscillatory activity in SMA negatively correlates with fatigue. • In patients, gamma- and beta- oscillatory activity is diminished in l-M1. Persistent fatigue is a major symptom of the so-called 'long-COVID syndrome', but the pathophysiological processes that cause it remain unclear. We hypothesized that fatigue after COVID-19 would be associated with altered cortical activity in premotor and motor regions. We used transcranial magnetic stimulation combined with EEG (TMS-EEG) to explore the neural oscillatory activity of the left primary motor area (l-M1) and supplementary motor area (SMA) in a group of sixteen post-COVID patients complaining of lingering fatigue as compared to a sample of age-matched healthy controls. Perceived fatigue was assessed with the Fatigue Severity Scale (FSS) and Fatigue Rating Scale (FRS). Post-COVID patients showed a remarkable reduction of beta frequency in both areas. Correlation analysis exploring linear relation between neurophysiological and clinical measures revealed a significant inverse correlation between the individual level of beta oscillations evoked by TMS of SMA with the individual scores in the FRS (r(15) = -0.596; p = 0.012). Post-COVID fatigue is associated with a reduction of TMS-evoked beta oscillatory activity in SMA. TMS-EEG could be used to identify early alterations of cortical oscillatory activity that could be related to the COVID impact in central fatigue. [ABSTRACT FROM AUTHOR]

Psychomotor disturbances are observed across psychiatric disorders and often manifest as psychomotor slowing, agitation, disorganized behavior, or catatonia. Psychomotor function includes both cognitive and motor components, but the neural circuits driving these subprocesses and how they relate to symptoms have remained elusive for centuries. We analyzed data from the HCP-EP (Human Connectome Project for Early Psychosis), a multisite study of 125 participants with early psychosis and 58 healthy participants with resting-state functional magnetic resonance imaging and clinical characterization. Psychomotor function was assessed using the 9-hole pegboard task, a timed motor task that engages mechanical and psychomotor components of action, and tasks assessing processing speed and task switching. We used multivariate pattern analysis of whole-connectome data to identify brain correlates of psychomotor function. We identified discrete brain circuits driving the cognitive and motor components of psychomotor function. In our combined sample of participants with psychosis (n = 89) and healthy control participants (n = 52), the strongest correlates of psychomotor function (pegboard performance) (p <.005) were between a midline cerebellar region and left frontal region and presupplementary motor area. Psychomotor function was correlated with both cerebellar-frontal connectivity (r = 0.33) and cerebellar–presupplementary motor area connectivity (r = 0.27). However, the cognitive component of psychomotor performance (task switching) was correlated only with cerebellar-frontal connectivity (r = 0.19), whereas the motor component (processing speed) was correlated only with cerebellar–presupplementary motor area connectivity (r = 0.15), suggesting distinct circuits driving unique subprocesses of psychomotor function. We identified cerebellar-cortical circuits that drive distinct subprocesses of psychomotor function. Future studies should probe relationships between cerebellar connectivity and psychomotor performance using neuromodulation. [ABSTRACT FROM AUTHOR]

Spatial proximity to important stimuli often induces impulsive behaviour. How we overcome impulsive tendencies is what determines behaviour to be adaptive. Here, we used virtual reality to investigate whether the spatial proximity of stimuli is causally related to the supplementary motor area (SMA) functions. In two experiments, we set out to investigate these processes using a virtual environment that recreates close and distant spaces to test the causal contributions of the SMA in spatial impulsivity. In an online first experiment (N = 93) we validated and measured the influence of distant stimuli using a go/no-go task with close (21 cm) or distant stimuli (360 cm). In experiment 2 (N = 28), we applied transcranial static magnetic stimulation (tSMS) over the SMA (double-blind, crossover, sham-controlled design) to test its computations in controlling impulsive tendencies towards close vs distant stimuli. Reaction times and error rates (omission and commission) were analysed. In addition, the EZ Model parameters (a, v, Ter and MDT) were computed. Close stimuli elicited faster responses compared to distant stimuli but also exhibited higher error rates, specifically in commission errors (experiment 1). Real stimulation over SMA slowed response latencies (experiment 2), an effect mediated by an increase in decision thresholds (a). Current findings suggest that impulsivity might be modulated by spatial proximity, resulting in accelerated actions that may lead to an increase of inaccurate responses to nearby objects. Our study also provides a first starting point on the role of the SMA in regulating spatial impulsivity. [ABSTRACT FROM AUTHOR]

Introduction: The conventional method of placing transcranial direct current stimulation (tDCS) electrodes is just above the target brain area. However, this strategy for electrode placement often fails to improve motor function and modulate cortical excitability. We investigated the effects of optimized electrode placement to induce maximum electrical fields in the leg regions of both M1 and SMA, estimated by electric field simulations in the T1 and T2-weighted MRIbased anatomical models, on motor performance and cortical excitability in healthy individuals. Methods: A total of 36 healthy volunteers participated in this randomized, triple-blind, sham-controlled experiment. They were stratified by sex and were randomly assigned to one of three groups according to the stimulation paradigm, including tDCS with (1) anodal and cathodal electrodes positioned over FCz and POz, respectively, (A-P tDCS), (2) anodal and cathodal electrodes positioned over POz and FCz, respectively, (P-A tDCS), and (3) sham tDCS. The sit-to-stand training following tDCS (2 mA, 10 min) was conducted every 3 or 4 days over 3 weeks (5 sessions total). Results: Compared to sham tDCS, A-P tDCS led to significant increases in the number of sit-to-stands after 3 weeks training, whereas P-A tDCS significantly increased knee flexor peak torques after 3 weeks training, and decreased shortinterval intracortical inhibition (SICI) immediately after the first session of training and maintained it post-training. Discussion: These results suggest that optimized electrode placement of the maximal EF estimated by electric field simulation enhances motor performance and modulates cortical excitability depending on the direction of current flow. [ABSTRACT FROM AUTHOR]

Recent evidence suggests a connection between hyperacusis and the motor system of the brain. For instance, our recent study reported that hyperacusis in participants with tinnitus and hearing loss is associated with smaller gray matter volumes in the supplementary motor area (SMA). Given that hearing loss can affect gray matter changes in tinnitus, this study aimed to determine if the changes reported in our previous findings of smaller SMA gray matter volumes in hyperacusis persist in the absence of hearing loss. Data for this study were gathered from four prior studies conducted between 2004 and 2019 at the University Medical Centre Groningen (UMCG). A total of 101 participants with tinnitus and either clinically normal hearing (normal hearing with tinnitus or NHT, n = 35) or bilateral sensorineural hearing loss (hearing loss with tinnitus or HLT, n = 66) were included across four studies. Hyperacusis was determined by a score of ≥22 on the Hyperacusis Questionnaire (HQ). In the NHT group, 22 (63%) participants scored ≥22 on the HQ (NHT with hyperacusis: mean age 44.1 years, 12 females), while in the HLT group, 25 (38%) participants scored ≥22 on the HQ (HLT with hyperacusis: mean age 59.5 years, 10 females). The 2 × 2 between-group ANOVAs revealed that hyperacusis is associated with smaller SMA gray matter volumes, regardless of hearing levels. Notably, the smaller SMA gray matter volumes in hyperacusis were primarily influenced by the attentional subscales of the HQ. The association between hyperacusis and the motor system may indicate a constant alertness to sounds and a readiness for motor action. [ABSTRACT FROM AUTHOR]

Abstract Spatial proximity to important stimuli often induces impulsive behaviour. How we overcome impulsive tendencies is what determines behaviour to be adaptive. Here, we used virtual reality to investigate whether the spatial proximity of stimuli is causally related to the supplementary motor area (SMA) functions. In two experiments, we set out to investigate these processes using a virtual environment that recreates close and distant spaces to test the causal contributions of the SMA in spatial impulsivity. In an online first experiment (N = 93) we validated and measured the influence of distant stimuli using a go/no-go task with close (21 cm) or distant stimuli (360 cm). In experiment 2 (N = 28), we applied transcranial static magnetic stimulation (tSMS) over the SMA (double-blind, crossover, sham-controlled design) to test its computations in controlling impulsive tendencies towards close vs distant stimuli. Reaction times and error rates (omission and commission) were analysed. In addition, the EZ Model parameters (a, v, Ter and MDT) were computed. Close stimuli elicited faster responses compared to distant stimuli but also exhibited higher error rates, specifically in commission errors (experiment 1). Real stimulation over SMA slowed response latencies (experiment 2), an effect mediated by an increase in decision thresholds (a). Current findings suggest that impulsivity might be modulated by spatial proximity, resulting in accelerated actions that may lead to an increase of inaccurate responses to nearby objects. Our study also provides a first starting point on the role of the SMA in regulating spatial impulsivity.

• Surgical strategy of en masse resection of gliomas in the SMA is presented. • A surgical strategy that preserves the cingulum and the FAT can help in preventing the occurrence of SMA syndrome. Anatomy and connections of the supplementary motor area (SMA) are studied essentially to analyze the SMA syndrome. Experience with surgical treatment of 19 tumors located in SMA is analyzed. The cortical anatomy and subcortical connectivity of the SMA was studied on ten previously frozen and formalin fixed human cadaveric brain specimens. The white fiber dissection was performed using Klingler's method. Nineteen patients with low grade gliomas in the region of the SMA treated surgically were clinically analyzed. The white fiber connections of the SMA include short arcuate connections with the pre-central, middle and inferior frontal gyri, the medial part of the SLF, the cingulum, the frontal aslant tract (FAT), the claustro-cortical fibers, the fronto-striatal tract and the crossed frontal aslant tract. All tumors were operated using en-masse surgical technique described by us and its subsequent modifications that focused on attempts towards preservation of related critical fiber tracts namely FAT, cingulum and corpus callosum presumed to be responsible for postoperative SMA syndrome. Eight patients developed an SMA syndrome in the immediate post-operative period. Eleven patients did not develop any post-operative neurological deficits. In all these 11 patients it was apparent that the cingulum, FAT and the corpus callosal fibers were preserved during surgery by modifying the tumor resection technique. SMA syndrome is a frequent occurrence following surgery in patients with tumors in the region of the SMA complex. Surgical strategy that preserves the cingulum and the FAT can prevent the occurrence of the SMA syndrome. [ABSTRACT FROM AUTHOR]

Background: The present study evaluated the therapeutic efficacy and tolerability of 10 transcranial direct current stimulation (tDCS) sessions in treatment-resistance obsessive-compulsive disorder (OCD) patients using a multisite double-blind sham-controlled design. Methods: Eighty treatment-resistance outpatients suffering from obsessivecompulsive disorder were randomized to receive either active or sham transcranial direct current stimulation. The cathode was positioned over the supplementary motor area and the anode over the right supraorbital area. Patients were evaluated at baseline, end of treatment (day 14), one-month follow-up (day 45), and three-month follow-up (day 105) on the Yale-Brown Obsessive Compulsive Scale. Results: Although a significant interaction between time and treatment was observed, the primary endpoint--measuring the change in Yale-Brown obsessive compulsive scale scores after two weeks--was not achieved. Conversely, the secondary endpoint, which concerned the change in Yale-Brown obsessive compulsive scale scores after three months, was successfully met. It is important to note, however, that there were no significant differences in the percentage of responders and remitters at any of the post-treatment assessments. This suggests that the treatment may not have had a clinically relevant impact. Patients well received the transcranial direct current stimulation treatment, indicating its good tolerability. Conclusion: This is the largest controlled trial using transcranial direct current stimulation in treatment-resistance obsessive-compulsive disorder patients. Our results indicate the importance of studying the placebo effect in transcranial direct current stimulation and the necessity to consider a long follow-up time to best evaluate the effects of the intervention. [ABSTRACT FROM AUTHOR]

Transcranial alternating current stimulation (tACS) is a noninvasive method for brain stimulation that artificially modulates oscillatory brain activity in the cortical region directly beneath the electrodes by applying a weak alternating current. Beta (β) oscillatory activity in the supplementary motor area (SMA) is involved in motor planning and maintenance, whereas gamma (γ) oscillatory activity is involved in the updating of motor plans. However, the effect of applying tACS to the SMA on motor learning has not yet been investigated. This study assessed the effects of applying tACS to the SMA on motor learning. Forty-two right-handed healthy adults (age 20.6 ± 0.5 years, 24 men and 18 women) were included. Motor learning was assessed using a visuomotor tracking task with pinch tension of the right thumb and right forefinger. Each trial lasted 60 s, and the error rates were measured. Conductive rubber electrodes were attached to the SMA and the left shoulder for tACS. Stimulation was applied at an intensity of 1.0 mA and frequencies of 70 and 20 Hz in the γ-tACS and β-tACS treatment groups, respectively. The sham group was only administered a fade-in/out. The visuomotor tracking task was performed for 10 trials before tACS and 10 trials after tACS. Two trials were conducted on the following day to determine motor skill retention. The average deviation measured during 60 s was considered the error value. Pre-stimulation learning rate was calculated as the change in error rate. Post-stimulation learning rate and retention rate were calculated as the change in error rate after stimulation and on the day after stimulation, respectively. In both the stimulation groups, differences in pre-stimulation learning, poststimulation learning, and retention rates were not significant. However, in the γ-tACS group, baseline performance and pre-stimulation learning rate were positively correlated with post-stimulation learning rate. Therefore, applying γ-tACS to the SMA can increase post-stimulation learning rate in participants exhibiting low baseline performance and high pre-stimulation learning rate. Our findings suggest that motor learning can be effectively enhanced by applying γ-tACS to the SMA based on an individual's motor and learning abilities. [ABSTRACT FROM AUTHOR]

Background: Post-stroke aphasia (PSA) is one of the most devastating symptoms after stroke, yet limited treatment options are available. Prolonged intermittent theta burst stimulation (piTBS) is a promising therapy for PSA. However, its efficacy remains unclear. Therefore, we aim to investigate the efficacy of piTBS over the left supplementary motor area (SMA) in improving language function for PSA patients and further explore the mechanism of language recovery. Methods: This is a randomized, double-blinded, sham-controlled trial. A total of 30 PSA patients will be randomly allocated to receive either piTBS stimulation or sham stimulation for 15 sessions over a period of 3 weeks. The primary outcome is the Western Aphasia Battery Revised (WAB-R) changes after treatment. The secondary outcomes include The Stroke and Aphasia Quality of Life Scale (SAQOL-39g), resting-state electroencephalogram (resting-state EEG), Event-related potentials (ERP), brain derived neurotrophic factor (BDNF). These outcome measures are assessed before treatment, after treatment, and at 4-weeks follow up. This study was registered in Chinese Clinical Trial Registry (No. ChiCTR23000203238). Discussion: This study protocol is promising for improving language in PSA patients. Resting-state EEG, ERP, and blood examination can be used to explore the neural mechanisms of PSA treatment with piTBS. Clinical trial registration: https://www.chictr.org.cn/index.html, ChiCTR 2300074533. [ABSTRACT FROM AUTHOR]

The frontal aslant tract (FAT) is a white matter tract connecting the superior frontal gyrus (SFG) to the inferior frontal gyrus (IFG). Its dorsal origin is identified in humans in the medial wall of the SFG, in the supplementary motor complex (SM-complex). However, empirical observation shows that many FAT fibres appear to originate from the dorsal, rather than medial, portion of the SFG. We quantitatively investigated the actual origin of FAT fibres in the SFG, specifically discriminating between terminations in the medial wall and in the convexity of the SFG. We analysed data from 105 subjects obtained from the Human Connectome Project (HCP) database. We parcelled the cortex of the IFG, dorsal SFG and medial SFG in several regions of interest (ROIs) ordered in a caudal-rostral direction, which served as seed locations for the generation of streamlines. Diffusion imaging data (DWI) was processed using a multi-shell multi-tissue CSD-based algorithm. Results showed that the number of streamlines originating from the dorsal wall of the SFG significantly exceeds those from the medial wall of the SFG. Connectivity patterns between ROIs indicated that FAT sub-bundles are segregated in parallel circuits ordered in a caudal-rostral direction. Such high degree of coherence in the streamline trajectory allows to establish pairs of homologous cortical parcels in the SFG and IFG. We conclude that the frontal origin of the FAT is found in both dorsal and medial surfaces of the superior frontal gyrus. [ABSTRACT FROM AUTHOR]

Although implicated in unsuccessful treatment, psychomotor deficits and their neurobiological underpinnings in bipolar (BD) and unipolar (UD) depression remain poorly investigated. Here, we hypothesized that motor performance deficits in depressed patients would relate to basal functional coupling of the hand primary motor cortex (M1) and the posterior cingulate cortex (PCC) with the supplementary motor area (SMA). We performed a longitudinal, naturalistic study in BD, UD and matched healthy controls comprising of two resting-state functional MRI measurements five weeks apart and accompanying assessments of motor performance using a finger tapping task (FTT). A subject-specific seed-based analysis describing functional connectivity between PCC-SMA as well as M1-SMA was conducted. The basal relationships with motor performance were investigated using linear regression models and all measures were compared across groups. Performance in FTT was impaired in BD in comparison to HC in both sessions. Behavioral performance across groups correlated significantly with resting state functional coupling of PCC–SMA, but not of M1-SMA regions. This relationship was partially reflected in a reduced PCC–SMA connectivity in BD vs HC in the second session. Exploratory evaluation of large-scale networks coupling (SMN–DMN) exhibited no correlation to motor performance. Our results shed new light on the association between the degree of disruption in the SMA–PCC anticorrelation and the level of motor impairment in BD. [ABSTRACT FROM AUTHOR]

The subthalamic nucleus (STN) receives cortical inputs via the hyperdirect and indirect pathways, projects to the output nuclei of the basal ganglia, and plays a critical role in the control of voluntary movements and movement disorders. STN neurons change their activity during execution of movements, while recent studies emphasize STN activity specific to cancelation of movements. To address the relationship between execution and cancelation functions, we examined STN activity in two Japanese monkeys (Macaca fuscata, both sexes) who performed a goal-directed reaching task with a delay that included Go, Cancel, and NoGo trials. We first examined responses to the stimulation of the forelimb regions in the primary motor cortex and/or supplementary motor area. STN neurons with motor cortical inputs were found in the dorsal somatomotor region of the STN. All these STN neurons showed activity changes in Go trials, suggesting their involvement in execution of movements. Part of them exhibited activity changes in Cancel trials and sustained activity during delay periods, suggesting their involvement in cancelation of planedmovements and preparation of movements, respectively. The STN neurons rarely showed activity changes in NoGo trials. Go- and Cancel-related activity was selective to the direction of movements, and the selectivity was higher in Cancel trials than in Go trials. Changes in Go- and Cancel-related activity occurred early enough to initiate and cancel movements, respectively. These results suggest that the dorsal somatomotor region of the STN, which receives motor cortical inputs, is involved in preparation and execution of movements and cancelation of planned movements. [ABSTRACT FROM AUTHOR]

Supplementary motor area syndrome (SMAS) represents a common neurosurgical sequela. The incidence and time frame of its occurrence have yet to be characterized after surgery for brain tumors. We examined patients suffering from a brain tumor preoperatively, postoperatively, and during follow-up examinations after three months, including fine motor skills testing and transcranial magnetic stimulation (TMS). 13 patients suffering from a tumor in the dorsal part of the superior frontal gyrus underwent preoperative, early postoperative, and 3-month follow-up testing of fine motor skills using the Jebsen-Taylor Hand Function Test (JHFT) and the Nine-Hole Peg Test (NHPT) consisting of 8 subtests for both upper extremities. They completed TMS for cortical motor function mapping. Test completion times (TCTs) were recorded and compared. No patient suffered from neurological deficits before surgery. On postoperative day one, we detected motor deficits in two patients, which remained clinically stable at a 3-month follow-up. Except for page-turning, every subtest indicated a significant worsening of function, reflected by longer TCTs (p < 0.05) in the postoperative examinations for the contralateral upper extremity (contralateral to the tumor manifestation). At 3-month follow-up examinations for the contralateral upper extremity, each subtest indicated significant worsening compared to the preoperative status despite improvement to the immediate postoperative level. We also detected significantly longer TCTs (p < 0.05) postoperatively in the ipsilateral upper extremity. This study suggests a long-term worsening of fine motor skills even three months after SMA tumor resection, indicating the necessity of targeted physical therapy for these patients. [ABSTRACT FROM AUTHOR]

It is well known that cortical damage may affect cognitive functions, whereas subcortical damage, especially brainstem stroke, would be far less likely to cause cognitive decline, resulting in this condition being overlooked. Few studies have focused on cognitive dysfunction after a pontine stroke. Here, we begin with describing our nine new case reports of in-depth neuropsychological findings from patients with pontine stroke. The dominant domain of cognitive dysfunction was commonly characterized by executive dysfunction, almost in line with previous studies. The severity was relatively mild. We give an overview of the available literature on cognitive decline following a pontine stroke. This is followed by discussions regarding the prognosis of the cognitive disabilities. Based on previous neuroimaging findings, we would like to get to the core of the neuropathology underlying the cognitive declines in the context of "diaschisis", a phenomenon of a broad range of brain dysfunctions remote from the local lesions. Specifically, our unique paper, with two modalities of neuroimaging techniques, may help us better understand the pathology. SPECT scans yield evidence of frontal and thalamic hyper-perfusion and cerebellar hypo-perfusion in patients with pontine stroke. Functional near-infrared spectroscopy, when focusing on the supplementary motor area (SMA) as one of the hyper-perfusion areas, exhibits that SMA responses may be subject to the severity of cognitive decline due to a pontine stroke and would also be related to the recovery. Finally, we posit that cognitive decline due to pontine stroke could be explained by the failure of hierarchical cognitive processing in the fronto–ponto–cerebellar–thalamic loop. [ABSTRACT FROM AUTHOR]

Different types of resistance to passive movement, i.e. hypertonia, were described in schizophrenia spectrum disorders (SSD) long before the introduction of antipsychotics. While these have been rediscovered in antipsychotic-naïve patients and their non-affected relatives, the existence of intrinsic hypertonia vs drug-induced parkinsonism (DIP) in treated SSD remains controversial. This integrative review seeks to develop a commonly accepted framework to specify the putative clinical phenomena, highlight conflicting issues and discuss ways to challenge each hypothesis and model through adversarial collaboration. The authors agreed on a common framework inspired from systems neuroscience. Specification of DIP, locomotor paratonia (LMP) and psychomotor paratonia (PMP) identified points of disagreement. Some viewed parkinsonian rigidity to be sufficient for diagnosing DIP, while others viewed DIP as a syndrome that should include bradykinesia. Sensitivity of DIP to anticholinergic drugs and the nature of LPM and PMP were the most debated issues. It was agreed that treated SSD should be investigated first. Clinical features of the phenomena at issue could be confirmed by torque, EMG and joint angle measures that could help in challenging the selectivity of DIP to anticholinergics. LMP was modeled as the release of the reticular formation from the control of the supplementary motor area (SMA), which could be challenged by the tonic vibration reflex or acoustic startle. PMP was modeled as the release of primary motor cortex from the control of the SMA and may be informed by subclinical echopraxia. If these challenges are not met, this would put new constraints on the models and have clinical and therapeutic implications. [ABSTRACT FROM AUTHOR]

Background: Resection of bilateral parasagittal meningiomas of the dominant cortex is challenging. Some postoperative consequences are difficult to predict due to their low incidence. However, it is essential to recognize reversible symptoms. Akinetic mutism is a devastating but reversible symptom that occurs after supplementary motor area (SMA) injury. This report aims to provide more information to support the clinical progression of this syndrome. Case Description: A 47-year-old woman presented with psychomotor retardation and subtle weakness, particularly on the left side. A palpable mass was identified at the head vertex. Magnetic resonance imaging revealed bilateral parasagittal meningiomas with bone and sinus invasion of the SMA. A craniotomy was performed to remove the intracapsular tumor. Two days after the operation, the patient developed gradual deterioration in her motor function until it became a lock-in-like syndrome. Then, 1.5 months after treatment in the hospital and rehabilitation unit, she gradually improved her motor, cognitive, and psychomotor skills. Total recovery was achieved after 1 year. Conclusion: Surgery for lesions involving bilateral SMA can cause akinetic mutism. The typical manifestation of this syndrome may be devastating. However, it is reversible, and patients can regain full motor and cognitive functions over time without specific treatments. It is crucial to persevere and continue to provide the best care to the patient until recovery. [ABSTRACT FROM AUTHOR]

Background and Hypothesis The integration of information that typifies working memory (WM) operation requires a flexible, dynamic functional relationship among brain regions. In schizophrenia, though WM capacity is prominently impaired at higher loads, the mechanistic underpinnings are unclear. As a result, we lack convincing cognitive remediation of load-dependent deficits. We hypothesize that reduced WM capacity arises from a disruption in dynamic functional connectivity when patients face cognitive demands. Study Design We calculate the dynamic voxel-wise degree centrality (dDC) across the functional connectome in 142 patients with schizophrenia and 88 healthy controls (HCs) facing different WM loads during an n-back task. We tested associations of the altered variability in dDC and clinical symptoms and identified intermediate connectivity configurations (clustered states) across time during WM operation. These analyses were repeated in another independent dataset of 169 subjects (102 with schizophrenia). Study Results Compared with HCs, patients showed an increased dDC variability of supplementary motor area (SMA) for the "2back vs. 0back" contrast. This instability at the SMA seen in patients correlated with increased positive symptoms and followed a limited "U-shape" pattern at rest-condition and 2 loads. In the clustering analysis, patients showed reduced centrality in the SMA, superior temporal gyrus, and putamen. These results were replicated in a constrained search in the second independent dataset. Conclusions Schizophrenia is characterized by a load-dependent reduction of stable centrality in SMA; this relates to the severity of positive symptoms, especially disorganized behaviour. Restoring SMA stability in the presence of cognitive demands may have a therapeutic effect in schizophrenia. [ABSTRACT FROM AUTHOR]

Resting tremor is the most common presenting motor symptom in Parkinson's disease (PD). The supplementary motor area (SMA) is a main target of the basal-ganglia-thalamo-cortical circuit and has direct, facilitatory connections with the primary motor cortex (M1), which is important for the execution of voluntary movement. Dopamine potentially modulates SMA and M1 activity, and both regions have been implicated in resting tremor. This study investigated SMA-M1 connectivity in individuals with PD ON and OFF dopamine medication, and whether SMA-M1 connectivity is implicated in resting tremor. Dual-site transcranial magnetic stimulation was used to measure SMA-M1 connectivity in PD participants ON and OFF levodopa. Resting tremor was measured using electromyography and accelerometry. Stimulating SMA inhibited M1 excitability OFF levodopa, and facilitated M1 excitability ON levodopa. ON medication, SMA-M1 facilitation was significantly associated with smaller tremor than SMA-M1 inhibition. The current findings contribute to our understanding of the neural networks involved in PD which are altered by levodopa medication and provide a neurophysiological basis for the development of interventions to treat resting tremor.

BackgroundThe present study evaluated the therapeutic efficacy and tolerability of 10 transcranial direct current stimulation (tDCS) sessions in treatment-resistance obsessive-compulsive disorder (OCD) patients using a multisite double-blind sham-controlled design.MethodsEighty treatment-resistance outpatients suffering from obsessive-compulsive disorder were randomized to receive either active or sham transcranial direct current stimulation. The cathode was positioned over the supplementary motor area and the anode over the right supraorbital area. Patients were evaluated at baseline, end of treatment (day 14), one-month follow-up (day 45), and three-month follow-up (day 105) on the Yale-Brown Obsessive Compulsive Scale.ResultsAlthough a significant interaction between time and treatment was observed, the primary endpoint—measuring the change in Yale-Brown obsessive compulsive scale scores after two weeks—was not achieved. Conversely, the secondary endpoint, which concerned the change in Yale-Brown obsessive compulsive scale scores after three months, was successfully met. It is important to note, however, that there were no significant differences in the percentage of responders and remitters at any of the post-treatment assessments. This suggests that the treatment may not have had a clinically relevant impact. Patients well received the transcranial direct current stimulation treatment, indicating its good tolerability.ConclusionThis is the largest controlled trial using transcranial direct current stimulation in treatment-resistance obsessive-compulsive disorder patients. Our results indicate the importance of studying the placebo effect in transcranial direct current stimulation and the necessity to consider a long follow-up time to best evaluate the effects of the intervention.Clinical trial registrationClinicalTrials.gov, identifier NCT03304600.

We present clinical observation of a 3-year-old child during recovery after acute hypoxic brain injury (freshwater drowning). Using diagnostic transcranial magnetic stimulation and magnetic resonance tractography with reconstruction of the corticospinal tract (CST) originated from the primary motor cortex and supplementary motor area (SMA), we determined that hypoxic brain injury induced activation of CST from the SMA. The period of reorganization was associated with the development of epileptiform patterns, that confirms the transient hyperexcitability of cortical neurons. Our findings indicate no recovery of motor function after acute hypoxic brain injury when CST originated only from SMA.

Objectives: This study aimed to comprehensively investigate the functional connectivity of ten sub-regions within the premotor and supplementary motor areas (Right and Left Premotor 6d1, 6d2, 6d3, and Right and Left pre-Supplementary Motor (presma) and SMA). Using advanced magnetic resonance imaging (MRI), the objective was to understand the neurophysiological integrative characteristics of these regions by examining their connectivity with eight distinct functional brain networks. While previous studies have largely treated these areas as homogeneous entities, there is a significant gap in our understanding of the specific roles and connectivity profiles of their distinct sub-regions. The goal was to uncover the roles of these regions beyond conventional motor functions, contributing to a more holistic understanding of brain functioning. Methods: The study involved 198 healthy volunteers, with the primary methodology being functional connectivity analysis using advanced MRI techniques. Ten sub-regions within the premotor and supplementary motor areas served as seed regions, and their connectivity with eight distinct brain regional functional networks, including the Sensorimotor, Dorsal Attention, Language, Frontoparietal, Default Mode, Cerebellar, Visual, and Salience networks, was investigated. This approach allowed for the exploration of synchronized activity between these critical brain areas, shedding light on their integrated functioning and relationships with other brain networks. Results: The study revealed a nuanced landscape of functional connectivity for the premotor and supplementary motor areas with the main functional brain networks. Despite their high functional connectedness within the motor network, these regions displayed diverse functional integrations with other networks. There was moderate connectivity with the Sensorimotor and Dorsal Attention networks, highlighting their roles in motor execution and attentional processes. However, connectivity with the Language, Frontoparietal, Default Mode, Cerebellar, Visual, and Salience networks was generally low, indicating a primary focus on motor-related tasks. Conclusions: This study emphasized the multifaceted roles of the sub-regions of the premotor and supplementary motor areas. Beyond their crucial involvement in motor functions, these regions exhibited varied functional integrations with different brain networks. The observed disparities, especially in the Sensorimotor and Dorsal Attention networks, indicated a nuanced and specialized involvement of these regions in diverse cognitive functions. By delineating the specific connectivity profiles of these sub-regions, this study addresses the existing knowledge gap and suggests unique and distinct roles for each brain area in sophisticated cognitive tasks beyond their conventional motor functions. The results suggested unique and distinct roles for each brain area in sophisticated cognitive tasks beyond their conventional motor functions. This study underscores the importance of considering the broader neurophysiological landscape to comprehend the intricate roles of these brain areas, contributing to ongoing efforts in unravelling the complexities of brain function.

Recent evidence suggests a connection between hyperacusis and the motor system of the brain. For instance, our recent study reported that hyperacusis in participants with tinnitus and hearing loss is associated with smaller gray matter volumes in the supplementary motor area (SMA). Given that hearing loss can affect gray matter changes in tinnitus, this study aimed to determine if the changes reported in our previous findings of smaller SMA gray matter volumes in hyperacusis persist in the absence of hearing loss. Data for this study were gathered from four prior studies conducted between 2004 and 2019 at the University Medical Centre Groningen (UMCG). A total of 101 participants with tinnitus and either clinically normal hearing (normal hearing with tinnitus or NHT, n = 35) or bilateral sensorineural hearing loss (hearing loss with tinnitus or HLT, n = 66) were included across four studies. Hyperacusis was determined by a score of ≥22 on the Hyperacusis Questionnaire (HQ). In the NHT group, 22 (63%) participants scored ≥22 on the HQ (NHT with hyperacusis: mean age 44.1 years, 12 females), while in the HLT group, 25 (38%) participants scored ≥22 on the HQ (HLT with hyperacusis: mean age 59.5 years, 10 females). The 2 × 2 between-group ANOVAs revealed that hyperacusis is associated with smaller SMA gray matter volumes, regardless of hearing levels. Notably, the smaller SMA gray matter volumes in hyperacusis were primarily influenced by the attentional subscales of the HQ. The association between hyperacusis and the motor system may indicate a constant alertness to sounds and a readiness for motor action.

Conventional transcranial direct‐current stimulation (tDCS) delivered to the primary motor cortex (M1) has been shown to enhance implicit motor sequence learning (IMSL). Conventional tDCS targets M1 but also the motor association cortices (MAC), making the precise contribution of these areas to IMSL presently unclear. We aimed to address this issue by comparing conventional tDCS of M1 and MAC to 4 * 1 high‐definition (HD) tDCS, which more focally targets M1. In this mixed‐factorial, sham‐controlled, crossover study in 89 healthy young adults, we used mixed‐effects models to analyse sequence‐specific and general learning effects in the acquisition and short‐ and long‐term consolidation phases of IMSL, as measured by the serial reaction time task. Conventional tDCS did not influence general learning, improved sequence‐specific learning during acquisition (anodal: M = 42.64 ms, sham: M = 32.87 ms, p =.041), and seemingly deteriorated it at long‐term consolidation (anodal: M = 75.37 ms, sham: M = 86.63 ms, p =.019). HD tDCS did not influence general learning, slowed performance specifically in sequential blocks across all learning phases (all p's <.050), and consequently deteriorated sequence‐specific learning during acquisition (anodal: M = 24.13 ms, sham: M = 35.67 ms, p =.014) and long‐term consolidation (anodal: M = 60.03 ms, sham: M = 75.01 ms, p =.002). Our findings indicate that the observed superior conventional tDCS effects on IMSL are possibly attributable to a generalized stimulation of M1 and/or adjacent MAC, rather than M1 alone. Alternatively, the differential effects can be attributed to cathodal inhibition of other cortical areas involved in IMSL by the 4 * 1 HD tDCS return electrodes, and/or more variable electric field strengths induced by HD tDCS, compared with conventional tDCS. [ABSTRACT FROM AUTHOR]

Background: The supplementary motor area (SMA) is important for motor and language function. Damage to the SMA may harm these functions, yet tools for a preoperative assessment of the area are still sparse. Objective: The aim of this study was to validate a mapping protocol using repetitive navigated transcranial magnetic stimulation (rnTMS) and extend this protocol for both hemispheres and lower extremities. Methods: To this purpose, the SMA of both hemispheres were mapped based on a finger tapping task for 30 healthy subjects (35.97 ± 15.11, range 21-67 years; 14 females) using rnTMS at 20 Hz (120% resting motor threshold (RMT)) while controlling for primary motor cortex activation. Points with induced errors were marked on the corresponding MRI. Next, on the identified SMA hotspot a bimanual finger tapping task and the Nine-Hole Peg Test (NHPT) were performed. Further, the lower extremity was mapped at 20 Hz (140%RMT) using a toe tapping task. Results: Mean finger tapping scores decreased significantly during stimulation (25.70taps) compared to baseline (30.48; p < 0.01). Bimanual finger tapping led to a significant increase in taps during stimulation (28.43taps) compared to unimanual tapping (p < 0.01). Compared to baseline, completion time for the NHPT increased significantly during stimulation (baseline: 13.6 s, stimulation: 16.4 s; p < 0.01). No differences between hemispheres were observed. Conclusion: The current study validated and extended a rnTMS based protocol for the mapping of the SMA regarding motor function of upper and lower extremity. This protocol could be beneficial to better understand functional SMA organisation and improve preoperative planning in patients with SMA lesions. [ABSTRACT FROM AUTHOR]

Featured Application: A general framework for functional integration evaluation of human brain is proposed, which effectively combines whole-brain functional connectivity analysis with effective connectivity analysis based on Dynamic Causal Modeling. Much effort has been devoted towards the identification of brain areas recruited during driving—as one of the most common motor skills of human beings. However, how driving experience impacts on the brain's intrinsic functional architecture has not been fully investigated. Using resting-state fMRI data collected from 20 taxi drivers and 20 nondrivers, this paper asks whether there exists specific brain network integration encoding driving behavior. First, to address this, we proposed a general framework combining whole-brain functional connectivity analysis with effective connectivity analysis based on spectral Dynamic Causal Modeling. The validation results indicated that the application of this framework could effectively discover the brain network that best explained the observed BOLD fluctuations. Second, by segmenting supplementary motor area (SMA) into pre-SMA and SMA proper sub-regions, we used the above framework and discovered a hierarchical architecture with pre-SMA located at the higher level in both driver and control groups. Third, we further evaluated the possibility that driving behavior could be encoded by directed connections among the hierarchy, and found that the effective connectivity from pre-SMA to left superior frontal gyrus could distinguish drivers from nondrivers with a sensitivity of 80%. Our findings provide a new paradigm for analyzing the brain's intrinsic functional integration, and may shed new light on the theory of neuroplasticity that training and experience can remodel the patterns of correlated spontaneous brain activity between specific processing regions. Meanwhile, from a methodological advantage perspective, our proposed framework takes the functional connectivity results as a prior, enabling subsequent spectral DCM to efficiently assess functional integration at a whole-brain scale, which is not available by only using other DCM methods, such as stochastic DCM or the State-of-the-Art multimodal DCM. [ABSTRACT FROM AUTHOR]

The mechanisms underlying bimanual coordination have not yet been fully elucidated. Here, we evaluated the clinical features of bimanual movement impairment in a patient following surgery for a frontal lobe tumor. The patient was an 80-year-old man who had undergone subtotal tumor resection for a tumor in the right superior frontal gyrus. Histological examination of the resected specimen led to the diagnosis of malignant lymphoma of the diffuse large B-cell type, and the patient subsequently received high-dose methotrexate-based chemotherapy. Postoperatively, the patient had difficulty with bimanual movement, and on the 5th postoperative day we found that the impairment could not be attributed to weakness. Temporal changes in the characteristics of manual movements were analyzed. Bimanual diadochokinesis (opening/closing of the hands, pronation/supination of the forearms, and sequential finger movements) was more disturbed than unilateral movements; in-phase movements were more severely impaired than anti-phase movements. Bimanual movement performance was better when cued using an auditory metronome. On the 15th postoperative day, movements improved. The present observations show that in addition to the disturbance of anti-phase bimanual movements, resection of the frontal lobe involving the supplementary motor area (SMA) and premotor cortex (PMC) can cause transient impairment of in-phase bimanual diadochokinesis, which can be more severe than the impairment of anti-phase movements. The effect of auditory cueing on bimanual skills may be useful in the diagnosis of anatomical localization of the superior frontal gyrus and functional localization of the SMA and PMC and in rehabilitation of patients with brain tumors, as in the case of degenerative movement disorders. [ABSTRACT FROM AUTHOR]

Background: Functional neurological disorder (FND) is a common neuropsychiatric condition with established diagnostic criteria and effective treatments but for which the underlying neuropathophysiological mechanisms remain incompletely understood. Recent neuroimaging studies have revealed FND as a multi-network brain disorder, unveiling alterations across limbic, self-agency, attentional/salience, and sensorimotor networks. However, the relationship between identified brain alterations and disease progression or improvement is less explored. Methods: This study included resting-state functional magnetic resonance imaging (fMRI) data from 79 patients with FND and 74 age and sex-matched healthy controls (HC). First, voxel-wise BOLD signal variability was computed for each participant and the group-wise difference was calculated. Second, we investigated the potential of BOLD signal variability to serve as a prognostic biomarker for clinical outcome in 47 patients who attended a follow-up measurement after eight months. Results: The results demonstrated higher BOLD signal variability in key networks, including the somatomotor, salience, limbic, and dorsal attention networks, in patients compared to controls. Longitudinal analysis revealed an increase in BOLD signal variability in the supplementary motor area (SMA) in FND patients who had an improved clinical outcome, suggesting SMA variability as a potential state biomarker. Additionally, higher BOLD signal variability in the left insula at baseline predicted a worse clinical outcome. Conclusion: This study contributes to the understanding of FND pathophysiology, emphasizing the dynamic nature of neural activity and highlighting the potential of BOLD signal variability as a valuable research tool. The insula and SMA emerge as promising regions for further investigation as prognostic and state markers.

Background: Motor disorders are one of the world's major scourges, and neuromotor rehabilitation is paramount for prevention and monitoring plans. In this scenario, exercises and motor tasks to be performed by patients are crucial to follow and assess treatments' progression and efficacy. Nowadays, in clinical environments, quantitative assessment of motor cortex activities during task execution is rare, due to the bulkiness of instrumentation and the need for immobility during measurements [e.g., functional magnetic resonance imaging (MRI)]. Functional near-infrared spectroscopy (fNIRS) can contribute to a better understanding of how neuromotor processes work by measuring motor cortex activity non-invasively in freely moving subjects. Aim: Exploit fNIRS to measure functional activation of the motor cortex area during arm-raising actions. Design: All subjects performed three different upper limbs motor tasks: arm raising (non-goal-oriented), arm raising and grasping (goal oriented), and assisted arm raising (passive task). Each task was repeated ten times. The block design for each task was divided into 5 seconds of baseline, 5 seconds of activity, and 15 seconds of recovery. Population: Sixteen healthy subjects (11 males and 5 females) with an average (+/- standard deviation) of 37.9 (+/- 13.0) years old. Methods: Cerebral hemodynamic responses have been recorded in two locations, motor cortex (activation area) and prefrontal cortex (control location) exploiting commercial time-domain fNIRS devices. Haemodynamic signals were analyzed, separating the brain cortex hemodynamic response from extracerebral hemodynamic variations. Results: The hemodynamic response was recorded in the cortical motor area for goal-oriented and not-goaloriented tasks, while no response was noticed in the control location (prefrontal cortex position). Conclusions: This study provides a basis for canonical upper limb motor cortex activations that can be potentially compared to pathological cerebral responses in patients. It also highlights the potential use of TD-fNIRS to study goal-oriented versus non-goaloriented motor tasks. Impact: the findings of this study may have implications for clinical rehabilitation by providing a better understanding of the neural mechanisms underlying goal-oriented versus non-goal-oriented motor tasks. This may lead to more effective rehabilitation strategies for individuals with motor disorders and a more effective diagnosis of motor dysfunction supported by objective and quantitative neurophysiological readings. [ABSTRACT FROM AUTHOR]

BackgroundThe supplementary motor area (SMA) is important for motor and language function. Damage to the SMA may harm these functions, yet tools for a preoperative assessment of the area are still sparse.ObjectiveThe aim of this study was to validate a mapping protocol using repetitive navigated transcranial magnetic stimulation (rnTMS) and extend this protocol for both hemispheres and lower extremities.MethodsTo this purpose, the SMA of both hemispheres were mapped based on a finger tapping task for 30 healthy subjects (35.97 ± 15.11, range 21–67 years; 14 females) using rnTMS at 20 Hz (120% resting motor threshold (RMT)) while controlling for primary motor cortex activation. Points with induced errors were marked on the corresponding MRI. Next, on the identified SMA hotspot a bimanual finger tapping task and the Nine-Hole Peg Test (NHPT) were performed. Further, the lower extremity was mapped at 20 Hz (140%RMT) using a toe tapping task.ResultsMean finger tapping scores decreased significantly during stimulation (25.70taps) compared to baseline (30.48; p

Intrinsic delays in sensory feedback can be detrimental for motor control. As a compensation strategy, the brain predicts the sensory consequences of movement via a forward model on the basis of a copy of the motor command. Using these predictions, the brain attenuates somatosensory reafference to facilitate the processing of exafferent information. Theoretically, this predictive attenuation is disrupted by (even minimal) temporal errors between the predicted and actual reafference; however, direct evidence of such disruption is lacking as previous neuroimaging studies contrasted nondelayed reafferent input with exafferent input. Here, we combined psychophysics with functional magnetic resonance imaging to test whether subtle perturbations in the timing of somatosensory reafference disrupt its predictive processing. Twenty-eight participants (14 women) generated touches on their left index finger by tapping a sensor with their right index finger. The touches on the left index finger were delivered close to the time of contact of the two fingers or with a temporal perturbation (i.e., 153ms delay). We found that such a brief temporal perturbation disrupted the attenuation of the somatosensory reafference at both the perceptual and neural levels, leading to greater somatosensory and cerebellar responses and weaker somatosensory connectivity with the cerebellum, proportional to the perceptual changes. We interpret these effects as the failure of the forward model to predictively attenuate the perturbed somatosensory reafference. Moreover, we observed increased connectivity of the supplementary motor area with the cerebellum during the perturbations, which could indicate the communication of the temporal prediction error back to the motor centers. [ABSTRACT FROM AUTHOR]

Methods: The supplementary motor area (SMA) is a cortical region, that is located on the medial surface of the frontal lobe entirely within the interhemispheric fissure between the primary motor cortex (PMC) and prefrontal cortex (PFC). This area is a heterogeneous region in its structure, as well as in its connections with other parts of the brain; on the basis of these differences, the pre-SMA and SMA-proper regions are distinguished in it. Numerous neural connections with other parts of the central nervous system (CNS) suggest the involvement of the SMA in many cognitive functions, and not only in higher motor ones, as previously was thought. In particular, in the dominant hemisphere, the SMA performs the speech function through the frontal oblique fascicle (FOF), a bundle of association fibers that connects the SMA with Broca's area. In the event of various pathologies affecting the SMA and after neurosurgical manipulations in this area, a variety of neurological disorders can occur both motor and verbal. With the damage of this cortical region in the dominant hemisphere, SMA syndrome (akinetic mutism) can occur. This paper provides a review of the anatomical, cytoarchitectonic, and functional features of the SMA, as well as a detailed description of the clinical picture of the lesion of this cortical region.

BackgroundMotor disorders are one of the world’s major scourges, and neuromotor rehabilitation is paramount for prevention and monitoring plans. In this scenario, exercises and motor tasks to be performed by patients are crucial to follow and assess treatments’ progression and efficacy. Nowadays, in clinical environments, quantitative assessment of motor cortex activities during task execution is rare, due to the bulkiness of instrumentation and the need for immobility during measurements [e.g., functional magnetic resonance imaging (MRI)]. Functional near-infrared spectroscopy (fNIRS) can contribute to a better understanding of how neuromotor processes work by measuring motor cortex activity non-invasively in freely moving subjects.AimExploit fNIRS to measure functional activation of the motor cortex area during arm-raising actions.DesignAll subjects performed three different upper limbs motor tasks: arm raising (non-goal-oriented), arm raising and grasping (goal oriented), and assisted arm raising (passive task). Each task was repeated ten times. The block design for each task was divided into 5 seconds of baseline, 5 seconds of activity, and 15 seconds of recovery.PopulationSixteen healthy subjects (11 males and 5 females) with an average (+/− standard deviation) of 37.9 (+/− 13.0) years old.MethodsCerebral hemodynamic responses have been recorded in two locations, motor cortex (activation area) and prefrontal cortex (control location) exploiting commercial time-domain fNIRS devices. Haemodynamic signals were analyzed, separating the brain cortex hemodynamic response from extracerebral hemodynamic variations.ResultsThe hemodynamic response was recorded in the cortical motor area for goal-oriented and not-goaloriented tasks, while no response was noticed in the control location (prefrontal cortex position).ConclusionsThis study provides a basis for canonical upper limb motor cortex activations that can be potentially compared to pathological cerebral responses in patients. It also highlights the potential use of TD-fNIRS to study goal-oriented versus non-goaloriented motor tasks. Impact: the findings of this study may have implications for clinical rehabilitation by providing a better understanding of the neural mechanisms underlying goal-oriented versus non-goal-oriented motor tasks. This may lead to more effective rehabilitation strategies for individuals with motor disorders and a more effective diagnosis of motor dysfunction supported by objective and quantitative neurophysiological readings.

Background: Damage to the supplementary motor area (SMA) can lead to impairments of motor and language function. A detailed preoperative mapping of functional boarders of the SMA could therefore aid preoperative diagnostics in these patients. Objective: The aim of this study was the development of a repetitive nTMS protocol for non-invasive functional mapping of the SMA while assuring effects are caused by SMA rather than M1 activation. Methods: The SMA in the dominant hemisphere of 12 healthy subjects (28.2 ± 7.7 years, 6 females) was mapped using repetitive nTMS at 20 Hz (120% RMT), while subjects performed a finger tapping task. Reductions in finger taps were classified in three error categories (=15% = no errors, 15-30% = mild, >30% significant). The location and category of induced errors was marked in each subject's individual MRI. Effects of SMA stimulation were then directly compared to effects of M1 stimulation in four different tasks (finger tapping, writing, line tracing, targeting circles). Results: Mapping of the SMA was possible for all subjects, yet effect sizes varied. Stimulation of the SMA led to a significant reduction of finger taps compared to baseline (BL: 45taps, SMA: 35.5taps; p < 0.01). Line tracing, writing and targeting of circles was less accurate during SMA compared to M1 stimulation. Conclusion: Mapping of the SMA using repetitive nTMS is feasible. While errors induced in the SMA are not entirely independent of M1, disruption of the SMA induces functionally distinct errors. These error maps can aid preoperative diagnostics in patients with SMA related lesions. [ABSTRACT FROM AUTHOR]

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by patterns in which unwanted thoughts and fears are evoked as obsessions and furthermore, compulsive behaviors are provoked repeatedly, with a prevalence rate of 2% of the population. These obsessive-compulsive symptoms disrupt daily life and cause great distress to the individual. At present, OCD is treated with antidepressants, mainly selective serotonin reuptake inhibitors, and psychotherapy, including the exposure and response prevention method. However, these approaches may only show a certain level of efficacy, and approximately 50% of patients with OCD show treatment resistance. This situation has led to the research and development of neuromodulation therapies, including transcranial magnetic stimulation treatment, for OCD worldwide in recent years. In this case series, we retrospectively analyzed the TMS registry data of continuous theta burst stimulation (cTBS) therapy targeting the bilateral supplementary motor cortex for six patients with OCD whose obsessive-compulsive symptoms had not improved with pharmacotherapy. The results suggest that treatment with cTBS for the bilateral supplementary motor area may reduce obsessive-compulsive symptoms in patients with OCD, despite the limitations of an open-label preliminary case series. The present findings warrant further validation with a randomized, sham-controlled trial with a larger sample size in the future. [ABSTRACT FROM AUTHOR]

Objective: Primary progressive apraxia of speech (PPAOS) is associated with imaging abnormalities in the lateral premotor cortex (LPC) and supplementary motor area (SMA). It is not known whether greater involvement of these regions in either hemisphere is associated with demographics, presenting, and/or longitudinal features. Methods: In 51 prospectively recruited PPAOS patients who completed [18F]‐fluorodeoxyglucose (FDG) positron emission tomography (PET), we classified patients as left‐dominant, right‐dominant, or symmetric, based on visual assessment of the LPC and SMA on FDG‐PET. SPM and statistical analyses of regional metabolic values were performed. Diagnosis of PPAOS was made if apraxia of speech was present and aphasia absent. Thirteen patients completed ioflupane‐123I (dopamine transporter [DAT]) scans. We compared cross‐sectional and longitudinal clinicopathological, genetic, and neuroimaging characteristics across the three groups, with area under the receiver‐operating curve (AUROC) determined as a measure of effect size. Results: In all, 49% of the PPAOS patients were classified as left‐dominant, 31% as right‐dominant, and 20% as symmetric, which was supported by results from the SPM and regional analyses. There were no differences in baseline characteristics. Longitudinally, right‐dominant PPAOS showed faster rates of progression of ideomotor apraxia (AUROC 0.79), behavioral disturbances (AUROC 0.84), including disinhibition symptoms (AUROC 0.82) and negative behaviors (AUROC 0.82), and parkinsonism (AUROC 0.75) compared to left‐dominant PPAOS. Symmetric PPAOS showed faster rates of dysarthria progression compared to left‐dominant (AUROC 0.89) and right‐dominant PPAOS (AUROC 0.79). Five patients showed abnormal DAT uptake. Braak neurofibrillary tangle stage differed across groups (p = 0.01). Conclusions: Patients with PPAOS and a right‐dominant pattern of hypometabolism on FDG‐PET have the fastest rates of decline of behavioral and motor features. [ABSTRACT FROM AUTHOR]

BackgroundTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that delivers constant, low electrical current resulting in changes to cortical excitability. Prior work suggests it may enhance motor learning giving it the potential to augment surgical technical skill acquisition.ObjectivesThe aim of this study was to test the efficacy of tDCS, coupled with motor skill training, to accelerate laparoscopic skill acquisition in a pre-registered (NCT03083483), double-blind and placebo-controlled study. We hypothesized that relative to sham tDCS, active tDCS would accelerate the development of laparoscopic technical skills, as measured by the Fundamentals of Laparoscopic Surgery (FLS) Peg Transfer task quantitative metrics.MethodsIn this study, sixty subjects (mean age 22.7 years with 42 females) were randomized into sham or active tDCS in either bilateral primary motor cortex (bM1) or supplementary motor area (SMA) electrode configurations. All subjects practiced the FLS Peg Transfer Task during six 20-min training blocks, which were preceded and followed by a single trial pre-test and post-test. The primary outcome was changes in laparoscopic skill performance over time, quantified by group differences in completion time from pre-test to post-test and learning curves developed from a calculated score accounting for errors.ResultsLearning curves calculated over the six 20-min training blocks showed significantly greater improvement in performance for the bM1 group than the sham group (t = 2.07, p = 0.039), with the bM1 group achieving approximately the same amount of improvement in 4 blocks compared to the 6 blocks required of the sham group. The SMA group also showed greater mean improvement than sham, but exhibited more variable learning performance and differences relative to sham were not significant (t = 0.85, p = 0.400). A significant main effect was present for pre-test versus post-test times (F = 133.2, p

BackgroundDamage to the supplementary motor area (SMA) can lead to impairments of motor and language function. A detailed preoperative mapping of functional boarders of the SMA could therefore aid preoperative diagnostics in these patients.ObjectiveThe aim of this study was the development of a repetitive nTMS protocol for non-invasive functional mapping of the SMA while assuring effects are caused by SMA rather than M1 activation.MethodsThe SMA in the dominant hemisphere of 12 healthy subjects (28.2 ± 7.7 years, 6 females) was mapped using repetitive nTMS at 20 Hz (120% RMT), while subjects performed a finger tapping task. Reductions in finger taps were classified in three error categories (≤15% = no errors, 15–30% = mild, >30% significant). The location and category of induced errors was marked in each subject’s individual MRI. Effects of SMA stimulation were then directly compared to effects of M1 stimulation in four different tasks (finger tapping, writing, line tracing, targeting circles).ResultsMapping of the SMA was possible for all subjects, yet effect sizes varied. Stimulation of the SMA led to a significant reduction of finger taps compared to baseline (BL: 45taps, SMA: 35.5taps; p

Much effort has been devoted towards the identification of brain areas recruited during driving—as one of the most common motor skills of human beings. However, how driving experience impacts on the brain’s intrinsic functional architecture has not been fully investigated. Using resting-state fMRI data collected from 20 taxi drivers and 20 nondrivers, this paper asks whether there exists specific brain network integration encoding driving behavior. First, to address this, we proposed a general framework combining whole-brain functional connectivity analysis with effective connectivity analysis based on spectral Dynamic Causal Modeling. The validation results indicated that the application of this framework could effectively discover the brain network that best explained the observed BOLD fluctuations. Second, by segmenting supplementary motor area (SMA) into pre-SMA and SMA proper sub-regions, we used the above framework and discovered a hierarchical architecture with pre-SMA located at the higher level in both driver and control groups. Third, we further evaluated the possibility that driving behavior could be encoded by directed connections among the hierarchy, and found that the effective connectivity from pre-SMA to left superior frontal gyrus could distinguish drivers from nondrivers with a sensitivity of 80%. Our findings provide a new paradigm for analyzing the brain’s intrinsic functional integration, and may shed new light on the theory of neuroplasticity that training and experience can remodel the patterns of correlated spontaneous brain activity between specific processing regions. Meanwhile, from a methodological advantage perspective, our proposed framework takes the functional connectivity results as a prior, enabling subsequent spectral DCM to efficiently assess functional integration at a whole-brain scale, which is not available by only using other DCM methods, such as stochastic DCM or the State-of-the-Art multimodal DCM.

Repetitive transcranial megnetic stimulation (rTMS) has been widely used in patients with psychiatric disorders. Previous studies revealed good efficacy of rTMS for patients with obsession-compulsive disorder (OCD) and Tic disorder (TD). OCD and TD are closely related and considered to etiologically overlap. Patients with the co-occurrence of OCD and TD are often identified. Therefore, we conducted a quick review of rTMS for the treatment of these two diseases to compare the similarities and differences of rTMS for OCD and TD, which might provide an indication for the treatment of the co-occurrence of OCD and TD. We searched articles published in PubMed, Wanfang, and Web of Science from January 2001 to January 2022. Both inclusion criteria and exclusion criteria were developed to identify the relevant included studies. Data on the frequency, target area, sample size, and number of males, especially the rTMS treatment procedure or parameters, were extracted in the included studies. We included 26 studies on OCD and 12 studies on TD in this quick review. A total of 996 participants were included. Based on the review of the included studies, lowfrequency rTMS might be used more than highfrequency rTMS, and the supplementary motor area (SMA) might show better efficacy than the dorsolateral prefrontal cortex (DLPFC) in OCD. For patients with TD, low-frequency rTMS located in the SMA might show good efficacy both in OCD and TD. Our quick review elaborated the treatment efficacy of rTMS for both patients with OCD and those with TD. It seems that the SMA is an important target choice for both OCD and TD patients. Low-frequency rTMS might be used more than high-frequency rTMS in both OCD and TD patients. In future studies, we should explore more about the efficacy of rTMS for patients with co-occurring OCD and TD, especially for the efficacy of targeted SMA with low frequency. [ABSTRACT FROM AUTHOR]

Background: Freezing of gait (FOG) is among the most common and disabling symptoms of Parkinson's disease (PD). Studies show that deep brain stimulation (DBS) of the subthalamic nucleus (STN) can reduce FOG severity. However, there is uncertainty about pathways that need to be modulated to improve FOG. Objective: To investigate whether STN-DBS effectively reduces FOG postoperatively and whether structural connectivity of the stimulated tissue explains variance of outcomes. Methods: We investigated 47 patients with PD and preoperative FOG. Freezing prevalence and severity was primarily assessed using the Freezing of Gait Questionnaire (FOG-Q). In a subset of 18 patients, provoked FOG during a standardized walking course was assessed. Using a publicly available model of basal-ganglia pathways we determined stimulation-dependent connectivity associated with postoperative changes in FOG. A region-of-interest analysis to a priori defined mesencephalic regions was performed using a disease-specific normative connectome. Results: Freezing of gait significantly improved six months postoperatively, marked by reduced frequency and duration of freezing episodes. Optimal stimulation volumes for improving FOG structurally connected to motor areas, the prefrontal cortex and to the globus pallidus. Stimulation of the lenticular fasciculus was associated with worsening of FOG. This connectivity profile was robust in a leave-one-out cross-validation. Subcortically, stimulation of fibers crossing the pedunculopontine nucleus and the substantia nigra correlated with postoperative improvement. Conclusion: STN-DBS can alleviate FOG severity by modulating specific pathways structurally connected to prefrontal and motor cortices. More differentiated FOG assessments may allow to differentiate pathways for specific FOG subtypes in the future. [ABSTRACT FROM AUTHOR]

Generally, the readiness potential (RP) is considered to be the scalp electroencephalography (EEG) activity preceding movement. In our previous study, we found early RP was absent among approximately half of the subjects during instructed action, but we did not identify the mechanism causing the disappearance of the RP. In this study, we investigated whether the time-estimation process could cause the disappearance of the RP. First, we designed experiments consisting of motor execution (ME), motor execution after time estimation (MEATE), and time estimation (TE) tasks, and we collected and preprocessed the EEG data of 16 subjects. Second, we compared the event related potential (ERP) waveform and scalp topography between ME and MEATE tasks. Then, to explore the influence of time-estimation, we analyzed the difference in ERP between MEATE and TE tasks. Finally, we used source imaging to probe the activation of brain regions during the three tasks, and we calculated the average activation amplitude of eight motor related brain regions. We found that the RP occurred in the ME task but not in the MEATE task. We also found that the waveform of the difference in ERP between the MEATE and TE tasks was similar to that of the ME task. The results of source imaging indicated that, compared to the ME task, the activation amplitude of the supplementary motor area (SMA) decreased significantly for the MEATE task. Our results suggested that the time estimation process could cause the disappearance of the RP. This phenomenon might be caused by the counteraction of neural electrical activity related to time estimation and motor preparation in the SMA. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by both motor and nonmotor symptoms. Although the basal ganglia is traditionally the primary brain region implicated in this disease process, this limited view ignores the roles of the cortex and cerebellum that are networked with the basal ganglia to support motor and cognitive functions. In particular, recent research has highlighted dysfunction in the supplementary motor complex (SMC) in patients with PD. Using the PubMed and Google Scholar search engines, we identified research articles using keywords pertaining to the involvement of the SMC in action sequencing impairments, temporal processing disturbances, and gait impairment in patients with PD. A review of abstracts and full-text articles was used to identify relevant articles. In this review of 63 articles, we focus on the role of the SMC in PD, highlighting anatomical and functional data to create new perspectives in understanding clinical symptoms and, potentially, new therapeutic targets. The SMC has a nuanced role in the pathophysiology of PD, with both hypo- and hyperactivation associated with various symptoms. Further studies using more standardized patient populations and functional tasks are needed to more clearly elucidate the role of this region in the pathophysiology and treatment of PD.

Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) characterized by paroxysmal episodes in which patients are unable to step forward. A research priority is identifying cortical changes before freezing in PD-FOG. We tested 19 patients with PD who had been assessed for FOG (n =14 with FOG and 5 without FOG). While seated, patients stepped bilaterally on pedals to progress forward through a virtual hallway while 64-channel EEG was recorded. We assessed cortical activities before and during lower limb motor blocks (LLMB), defined as a break in rhythmic pedaling, and stops, defined as movement cessation following an auditory stop cue. This task was selected because LLMB correlates with FOG severity in PD and allows recording of high-quality EEG. Patients were tested after overnight withdrawal from dopaminergic medications ("off" state) and in the "on" medications state. EEG source activities were evaluated using individual MRI and standardized low resolution brain electromagnetic tomography (sLORETA). Functional connectivity was evaluated by phase lag index between seeds and pre-defined cortical regions of interest. EEG source activities for LLMB vs. cued stops localized to right posterior parietal area (Brodmann area 39), lateral premotor area (Brodmann area 6), and inferior frontal gyrus (Brodmann area 47). In these areas, PD-FOG (n =14) increased alpha rhythms (8-12 Hz) before LLMB vs. typical stepping, whereas PD without FOG (n =5) decreased alpha power. Alpha rhythms were linearly correlated with LLMB severity, and the relationship became an inverted U-shape when assessing alpha rhythms as a function of percent time in LLMB in the "off" medication state. Right inferior frontal gyrus and supplementary motor area connectivity was observed before LLMB in the beta band (13-30 Hz). This same pattern of connectivity was seen before stops. Dopaminergic medication improved FOG and led to less alpha synchronization and increased functional connections between frontal and parietal areas. Right inferior parietofrontal structures are implicated in PD-FOG. The predominant changes were in the alpha rhythm, which increased before LLMB and with LLMB severity. Similar connectivity was observed for LLMB and stops between the right inferior frontal gyrus and supplementary motor area, suggesting that FOG may be a form of "unintended stopping." These findings may inform approaches to neurorehabilitation of PD-FOG. • Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD). • EEG source activity localized to right frontal and parietal areas in PD-FOG. • Alpha rhythms in these areas increased with severity of lower limb motor blocks. • Dopaminergic medications improved FOG and led to fewer alpha rhythms. • These brain signals may be useful for neurorehabilitation of PD-FOG. [ABSTRACT FROM AUTHOR]