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• 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]

• 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]

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]

After resective glioma surgery in the Supplementary Motor Area (SMA), patients often experience a transient disturbance of the ability to initiate speech and voluntary motor actions, known as the SMA syndrome (SMAS). It has been proposed that enhanced interhemispheric functional connectivity (FC) within the sensorimotor system may serve as a potential mechanism for recovery, enabling the non-resected SMA to assume the function of the resected region. The purpose of the present study was to investigate the extent to which changes in FC can be observed in patients after resolution of the SMAS. Eight patients underwent resection of left SMA due to suspected gliomas, resulting in various levels of the SMA syndrome. Resting-state functional MR images were acquired prior to the surgery and after resolution of the syndrome. At the group level we found an increased connectivity between the unaffected (right) SMA and the primary motor cortex on the same side following surgery. However, no significant increase in interhemispheric connectivity was observed. These findings challenge the prevailing notion that increased interhemispheric FC serves as the only mechanism underlying recovery from SMA syndrome and suggest the presence of one or more alternative mechanisms. • Resection of the SMA leads to transient disturbance of speech and motor function. • Recovery have been suggested to depend on SMA in healthy hemisphere. • Resting State fMRI found no increased connection to healthy hemisphere. • Patients, who recovered, showed no increased connection to healthy hemisphere. • Activation of healthy SMA cannot be the only mechanism of recovery. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of continuous theta burst stimulation (cTBS) on the bilateral supplementary motor area (SMA) among patients with obsessive-compulsive disorder (OCD) and to explore the potential predictors of cTBS outcome based on neuroimaging.Methods: 29 OCD patients and 29 healthy controls (HCs) were enrolled in this pilot study. Twenty consecutive cTBS intervention targeting at bilateral SMA was applied. MRI scan was carried out before cTBS and 15 regions in the executive control and sensorimotor network were chosen and analyzed using MATLAB, DPABI, and SPM12.Results: 11 out of 29 patients responded to cTBS (37.93%), and the clinical symptom of OCD patients was significantly relieved after receiving regular cTBS. Also, the FC between Cerebelum_Crus2_L and Frontal_Inf_Tri_L of OCD patients showed positive prognosis for the efficacy of cTBS, with the area under the curve (AUC) of 0.85 (95% confidence interval: 0.718-0.989, p = 0.002). None of the patients had any serious adverse event.Conclusion: cTBS intervention on bilateral SMA can significantly improve the symptoms of medicated OCD patients with moderate severity. And the pretherapy FC could be a valuable potential predictor of the cTBS treatment outcome among OCD patients. [ABSTRACT FROM AUTHOR]

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. We report inter-M1 cortico-cortical evoked potential (CCEP) recording during asleep resection of a bilateral parasagittal meningioma with intraoperative neuromonitoring and motor mapping. CCEPs were recorded between both M1 cortices with bipolar stimulations of both supplementary motor areas (10.5–11.5 μV). 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. [ABSTRACT FROM AUTHOR]

• fMRI meta-analysis used to identify neural correlates of effort-based valuation. • vmPFC activity scales positively with net value and negatively with effort costs. • pre-SMA ROI has an opposite pattern of activation. • vmPFC is a candidate region for domain-general cost/benefit value integration. Choosing how much effort to expend is critical for everyday decisions. While several neuroimaging studies have examined effort-based decision-making, results have been highly heterogeneous, leaving unclear which brain regions process effort-related costs and integrate them with rewards. We conducted two meta-analyses of functional magnetic resonance imaging data to examine consistent neural correlates of effort demands (23 studies, 15 maps, 549 participants) and net value (15 studies, 11 maps, 428 participants). The pre-supplementary motor area (pre-SMA) scaled positively with pure effort demand, whereas the ventromedial prefrontal cortex (vmPFC) showed the opposite effect. Moreover, regions that have been previously implicated in value integration in other cost domains, such as the vmPFC and ventral striatum, were consistently involved in signaling net value. The opposite response patterns of the pre-SMA and vmPFC imply that they are differentially involved in the representation of effort costs and value integration. These findings provide conclusive evidence that the vmPFC is a central node for net value computation and reveal potential brain targets to treat motivation-related disorders. [ABSTRACT FROM AUTHOR]

• Hypoactivation in the supplementary motor area (SMA) has been associated with bradykinesia in Parkinson's Disease. • Movement speed was assessed following anodal or sham tDCS applied over SMA. • Anodal tDCS improved movement kinematics, but did not impact premotor RT. Bradykinesia, defined as slowness of movements, is among the most functionally debilitating symptoms of Parkinson's disease (PD). Hypoactivation of cortical neurons in supplementary motor area (SMA) has been linked to the progression of bradykinesia symptoms. This study investigated the influence of transcranial direct current stimulation (tDCS) applied over SMA on upper limb movement for individuals diagnosed with PD. Thirteen individuals with PD performed a simple reaction time (RT) task involving elbow extension following an auditory go-signal. Sham or anodal tDCS was then applied over SMA for 10 minutes before participants repeated the simple RT task. Participants were unaware of which stimulation they received in each testing session. Electromyography (EMG) and kinematic data were recorded on all trials. While there were no significant differences in premotor RT, anodal tDCS applied over SMA led to significantly shorter time to peak displacement (p =.015) and movement time (p =.003) compared to pre-tDCS trials, whereas sham stimulation had no impact on these variables. These results provide evidence that anodal tDCS applied over SMA contributes to improvements in movement kinematics of an upper limb simple RT task. Anodal tDCS over SMA could be a useful therapy to mitigate bradykinesia associated with PD. [ABSTRACT FROM AUTHOR]

Background: The supplementary motor area (SMA) is implicated in stereotypic multi-limb movements such as walking with arm swing. Gait difficulties in Parkinson's Disease (PD) include reduced arm swing, which is associated with reduced SMA activity.Objective: To test whether enhanced arm swing improves Parkinsonian gait and explore the role of the SMA in such an improvement.Methods: Cortical activity and gait characteristics were assessed by ambulant EEG, accelerometers and video recordings in 27 PD patients with self-reported gait difficulties and 35 healthy participants when walking normally. Within these two groups, 19 PD patients additionally walked with enhanced arm swing and 30 healthy participants walked without arm swing. Power changes across the EEG frequency spectrum were assessed by Event Related Spectral Perturbation analysis of recordings from Fz over the putative SMA and gait analysis was performed.Results: Baseline PD gait, characterized by reduced arm swing among other features, exhibited reduced within-step Event Related Desynchronization (ERD)/Synchronization (ERS) alternation (Fz; 20-50Hz), accompanied by a reduced step length and walking speed. All became similar to normal gait when patients walked with enhanced arm swing. When healthy controls walked without arm swing, their alternating ERD-ERS pattern decreased, mimicking baseline PD gait.Conclusion: Enhanced arm swing may serve as a driving force to overcome impaired gait control in PD patients by restoring reduced ERD-ERS alternation over the putative SMA. Accompanied by increased step length and walking speed, this provides a neural underpinning of arm swing as an effective rehabilitation concept for improving Parkinsonian gait. [ABSTRACT FROM AUTHOR]

intrusive thoughts and compulsive behaviors that characterize obsessive compulsive disorder (OCD) are associated to aberrant resting state functional connectivity (rsFC) patterns within the cortico-striatal-thalamo-cortical (CSTC) circuits. A high percentage of OCD patients do not respond to conventional pharmacological treatments or psychotherapy. In these patients, inhibitory repetitive transcranial magnetic stimulation (rTMS) of the Supplementary Motor Area (SMA) resulted in a significant clinical benefit. In the current study, we applied a novel protocol of 1-week MRI-guided individualized double-daily sessions of rTMS treatment (1-Hz; 110% of resting Motor Threshold/7200 pulses/day), to bilateral SMA in 9 OCD patients. We tested its (i) feasibility-safety, (ii) clinical efficacy and (iii) rsFC related changes. Patients reported no side effects during and after rTMS. Personalized rTMS treatment led to a significant improvement of OCD symptoms (average 25%; p =.005) and persistence of benefit up to 3-month follow-up. rsFC analysis revealed a significant reduction of connectivity patterns between bilateral SMA and subcortical regions, specifically in the basal ganglia and thalamus. Additional analysis showed that OCD symptoms severity correlates with a higher connectivity pattern between bilateral SMA and subcortical regions. rTMS double-daily sessions are safe, feasible and effective in OCD. The clinical outcomes, that are consistent with those found in our previous RCT, are linked to a decreased connectivity between SMA and subcortical brain areas implicated in control over obsessions and maladaptive compulsive behavior. • Double-daily fMRI-guided rTMS applied to the SMA is safe and feasible. • Individualized rTMS significantly improves both obsessions and compulsions. • The clinical effect of rTMS persists in the long-term follow-up. • RTMS to the SMA induces a significant reduction in the rsFC within the CSTC circuit. • Clinical improvements by rTMS correlate with changes in rsFC. [ABSTRACT FROM AUTHOR]

Beat perception offers cognitive scientists an exciting opportunity to explore how cognition and action are intertwined in the brain even in the absence of movement. Many believe the motor system predicts the timing of beats, yet current models of beat perception do not specify how this is neurally implemented. Drawing on recent insights into the neurocomputational properties of the motor system, we propose that beat anticipation relies on action-like processes consisting of precisely patterned neural time-keeping activity in the supplementary motor area (SMA), orchestrated and sequenced by activity in the dorsal striatum. In addition to synthesizing recent advances in cognitive science and motor neuroscience, our framework provides testable predictions to guide future work. Components of the brain's motor system are activated by the perception of a musical beat, even in the absence of movement, and may play an important role in beat-based temporal prediction. Two key brain regions involved in movement, the supplementary motor area (SMA) and dorsal striatum, have neurocomputational properties that lend themselves to beat perception. In SMA, neural firing rates represent the phase of cyclic sensorimotor processes. The involvement of SMA in perceptual suppression of self-generated sounds suggests that it could play a broader role in informing auditory expectations. The dorsal striatum plays a central role in initiating and sequencing units of movement, and may serve similar functions in structuring beat-based temporal anticipation. [ABSTRACT FROM AUTHOR]

Background: Noninvasive brain stimulation (NIBS) was recently used as a therapeutic application in patients with insomnia. Most of the previous NIBS treatments for insomnia directly selected the dorsolateral prefrontal cortex (DLPFC) as the stimulation site. As the NIBS target is an important factor in the efficacy of NIBS, it is necessary to detect more potential cortical sites for NIBS in insomnia.Methods: A neuroimaging study-based meta-analysis was used to examine sleep-related brain regions. A sleep-associated brain region-based functional connectivity (FC) map was constructed in 50 patients with chronic insomnia disorder (CID) without any comorbidity. We also combined the meta-analysis and FC results to examine the potential surface targets for NIBS for CID.Results: The results identified the bilateral supplementary motor area (SMA), left superior temporal gyrus (STG), bilateral DLPFC, precentral lobule, supramarginal gyrus, angular gyrus, superior frontal gyrus, middle temporal gyrus and middle occipital gyrus as potential brain stimulation targets for insomnia treatment. Notably, the bilateral SMA, right DLPFC and left STG were identified in the FC and meta-analyses. In addition, the SMA and DLPFC were positively and STG was negatively connected with other sleep related brain regions, which indicated inhibitory and excitatory stimulation for NIBS treatment for CID, respectively.Conclusion: Our study suggests the SMA, DLPFC and STG as preferentially selected brain targets of NIBS for CID treatment. We recommend an inhibitory stimulation over SMA and DLPFC, and an excitatory stimulation over STG for NIBS treatment. Future studies should test these new targets using NIBS treatment for insomnia. [ABSTRACT FROM AUTHOR]

Activity in the supplementary motor area (SMA) has been associated with tics in Tourette syndrome (TS). The aim of this study was to test a novel intervention—real-time functional magnetic resonance imaging neurofeedback from the SMA—for reduction of tics in adolescents with TS. Twenty-one adolescents with TS were enrolled in a double-blind, randomized, sham-controlled, crossover study involving two sessions of neurofeedback from their SMA. The primary outcome measure of tic severity was the Yale Global Tic Severity Scale administered by an independent evaluator before and after each arm. The secondary outcome was control over the SMA assessed in neuroimaging scans, in which subjects were cued to increase/decrease activity in SMA without receiving feedback. All 21 subjects completed both arms of the study and all assessments. Participants had significantly greater reduction of tics on the Yale Global Tic Severity Scale after real neurofeedback as compared with the sham control (p <.05). Mean Yale Global Tic Severity Scale Total Tic score decreased from 25.2 ± 4.6 at baseline to 19.9 ± 5.7 at end point in the neurofeedback condition and from 24.8 ± 8.1 to 23.3 ± 8.5 in the sham control condition. The 3.8-point difference is clinically meaningful and corresponds to an effect size of 0.59. However, there were no differences in changes on the secondary measure of control over the SMA. This first randomized controlled trial of real-time functional magnetic resonance imaging neurofeedback in adolescents with TS suggests that this neurofeedback intervention may be helpful for improving tic symptoms. However, no effects were found in terms of change in control over the SMA, the hypothesized mechanism of action. [ABSTRACT FROM AUTHOR]

To propose a method for intraoperative mapping and monitoring of the medial frontal motor areas (MFMA). We estimated the location of the MFMA using the corticocortical evoked potential (CCEP) provoked by electric stimuli to the primary motor area (M1) of the upper limb. We localized or defined the MFMA by recording the motor evoked potentials (MEPs) provoked by electric stimuli to the medial frontal cortex around the estimated area. We monitored the patients' motor function during awake craniotomy and sequentially recorded the MEPs of the upper and/or lower limbs. This method was applied to 8 patients. Four patients who had part of the areas identified as the MFMA removed showed transient hemiparesis postoperatively (supplementary motor area [SMA] syndrome). The MEP from the M1 was preserved in the 4 patients. The resection of the identified MFMA might have caused their SMA syndrome. The CCEP showed a strong connection between the M1 and the SMA of the upper limb. Our method did not provoke any seizures. This is a safe and sensitive method for intraoperative mapping and monitoring of the MFMA by combining electrophysiologic monitoring and awake craniotomy. It is clinically useful for mapping the MFMA and can prevent permanent motor deficits. [ABSTRACT FROM AUTHOR]

• IP led to poor training performance but superior test performance compared to RP. • Consolidation within 6-h of finishing IP led to less forgetting than after RP. • Sleep-related consolidation after IP not RP, improved performance for the next 72-h. • Applying anodal tDCS at SMA during RP facilitated sleep-related consolidation. Interleaved rather than repetitive practice (RP) is associated with superior retention of motor skills. It has been argued that this results from improved post-practice consolidation reflected in greater offline gains following interleaved practice (IP). The magnitude of this offline benefit has been associated with greater recruitment of supplementary motor area (SMA) during encoding. The present study administered anodal or cathodal transcranial direct current stimulation (tDCS) during interleaved or RP respectively in an attempt to modify the activity at SMA and the concomitant retention outcomes commonly associated with these training formats. Sixty-nine participants were assigned to one of four experimental conditions that included: IP-sham, RP-sham, IP-cathodal tDCS, and RP-anodal tDCS. Real or sham stimulation at SMA was administered during practice of three unique 6-key discrete sequence production tasks which lasted approximately 20-min. Tests were administered prior to practice and immediately after practice as well at 6-h, 24-h, and 72-h after practice ended. As anticipated, IP resulted in poorer acquisition but superior offline gain. Enhanced offline gain following interleaved training resulted from rapid stabilization of performance within the first 6-h following encoding and overnight improvement that continued over multiple sleep episodes. Administration of anodal stimulation at SMA during RP improved performance during training compared to sham but this benefit was short lived as forgetting during the first 6-h after practice was consistent with that observed for the sham counterpart. However, supplementing RP with anodal stimulation at SMA did foster overnight offline performance gains not displayed by individuals that experienced RP in the absence of stimulation. [ABSTRACT FROM AUTHOR]

Transcranial 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. The 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. In 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. Learning 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 < 0.001), with lower completion times at post-test, however these did not significantly differ for the training groups. Laparoscopic skill training with active bilateral tDCS exhibited significantly greater learning relative to sham. The potential for tDCS to enhance the training of surgical skills, therefore, merits further investigation to determine if these preliminary results may be replicated and extended. • Active tDCS to the primary motor cortex led to accelerated surgical skill learning. • Subjects with active tDCS reached the same level of skill in two thirds the time. • SMA configuration had more variability than bilateral primary motor cortex. [ABSTRACT FROM AUTHOR]

• Protocol design of fMRI neurofeedback intervention for tics. • Using different type of control condition than prior trial. Novel approach for finding independent target region for control condition. • Performance based payment to mitigate waning motivation. This article describes the protocol for a randomized, controlled clinical trial of a neurofeedback (NF) intervention for Tourette Syndrome (TS) and chronic tic disorder. The intervention involves using functional magnetic resonance imaging (fMRI) to provide feedback regarding activity in the supplementary motor area: participants practice controlling this brain area while using the feedback as a training signal. The previous version of this NF protocol was tested in a small study (n = 21) training adolescents with TS that yielded clinically promising results. Therefore, we plan a larger trial. Here we describe the background literature that motivated this work, the design of our original neurofeedback study protocol, and adaptations of the research study protocol for the new trial. We focus on those ideas incorporated into our protocol that may be of interest to others designing and running NF studies. For example, we highlight our approach for defining an unrelated brain region to be trained in the control group that is based on identifying a region with low functional connectivity to the target area. Consistent with a desire for transparency and open science, the new protocol is described in detail here prior to conducting the trial. [ABSTRACT FROM AUTHOR]

Obsessive-compulsive disorder (OCD) is a complex disorder with 40 to 60 % of patients resistant to treatment. Theta burst transcranial magnetic stimulation (TBS) is a promising new technique that has been shown to induce potent and long lasting effects on cortical excitability. The present study evaluated for the first time therapeutic efficacy and tolerability of continuous TBS (cTBS) over the supplementary motor area (SMA) in treatment resistant OCD patients using a double blind, sham-controlled design. Thirty treatment resistant OCD outpatients were randomized to receive either active cTBS or sham cTBS for 6 weeks (5 sessions per week). Each treatment session consisted of 600 stimuli at an intensity of 70% of resting motor threshold. Patients were evaluated at baseline, at the end of treatment (week 6), and follow-up (week 12). Response to treatment was defined as at least 25% decrease on the Yale-Brown Obsessive Compulsive Scale. There was no significant difference between active and sham cTBS groups in treatment efficacy. Responder rates were not different between the two groups at week 6 (cTBS 28% versus sham 36%; p = 0.686) and week 12 (cTBS 28% versus sham 36%; p = 0.686). Depressive and anxious symptoms improvements were similar in the two groups. This study is the first controlled trial using cTBS in treatment resistant OCD patients. The use of cTBS over the SMA is safe but not sufficient to improve OCD symptoms. Further studies are needed to identify the optimal parameters to be used in OCD patients. • High powered randomized controlled trial testing the efficacy of continuous theta burst stimulation (cTBS) in OCD. • cTBS was used over multiple sessions to inhibit the supplementary motor area. • Overall, cTBS was well tolerated. • Active cTBS failed to reduce OCD symptoms, compared to sham cTBS. • Active cTBS failed to reduce depressive and anxious symptoms, compared to sham cTBS. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) has been linked to abnormal functioning of cortical motor areas such as the supplementary motor area, the premotor cortex and primary motor cortex (MI). The Bereitschaftspotential (BP) and lateralized readiness potential (LRP) are movement-related potentials generated by cortical motor areas. We hypothesized that the BP and LRP would be altered in children with ADHD. A group of 17 children with ADHD (mean age: 11.5 ± 1.9 years) and a control group of 16 typically developing children (mean age: 12.2 ± 2.0 years) performed movements at self-chosen irregular intervals while a 64-channel DC-EEG was registered. BP and LRP were calculated from the EEG. The ADHD group had significantly lower and on average positive BP amplitudes at Cz. In agreement with age-dependent maturation effects the LRP had a positive polarity in both groups, but lower amplitudes were found in the ADHD group without medication. The control group showed a mid-central negativity and a positivity over motor areas contra-lateral to the side of movement, whereas no negativity over Cz and a more diffuse positivity was found in the ADHD group. LRP group differences diminished after MPH administration as indicated by an interaction between group and time of measurement/medication. The cortical motor system shows altered functioning during movement preparation and initiation in children affected by ADHD. Positive Bereitschaftspotential polarities may represent delayed cortical maturation. Group differences of LRP were pharmacologically modulated by the catecholaminergic agent MPH. [ABSTRACT FROM AUTHOR]

Abstract Ageing is associated with a decline in motor function that critically interferes with activities of daily living involving manual dexterity. Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that has been shown to enhance manual dexterity in healthy aging adults. The supplementary motor area (SMA) is involved in motor preparation and bimanual control; therefore, bihemispheric tDCS incorporating the SMA may preferentially enhance bimanual motor movements in healthy older adults. The aim of the current study was to determine if tDCS incorporating SMA could improve manual dexterity in older adults. Twenty-four adults, aged 67–84 participated in this double-blind, randomized, cross over design, pilot study. One group of participants (n = 17) were randomized to receive stimulation or sham on their first visit and received the contrary on their second visit, seven days later. A second group of participants (n = 10) received three consecutive days of tDCS while performing a motor task. Participants performed unimanual and bimanual hand movements while receiving 2 mA of tDCS. The total time for participants to complete three trials of each task was recorded. No significant differences in performance times were observed between single or tri session tDCS and sham conditions. However, tDCS had opposing effects on the motor consolidation of anti-phase and in-phase bimanual tasks. During the tri session paradigm, older adults improved performance learning of antiphase bimanual movements more quickly than inphase bimanual movements, suggesting a different mechanism of action of these two movements. [ABSTRACT FROM AUTHOR]

• The primate nervous system exhibits both motor-cognitive links and gradients. • A convergence of data suggests that the motor network supports working memory. • Formation of internal motor traces may prolong working memory rehearsal. • Disrupted motor-cognitive network links may contribute to cognitive deficits. Working memory is vital for basic functions in everyday life. During working memory, one holds a finite amount of information in mind until it is no longer required or when resources to maintain this information are depleted. Convergence of neuroimaging data indicates that working memory is supported by the motor system, and in particular, by regions that are involved in motor planning and preparation, in the absence of overt movement. These "secondary motor" regions are physically located between primary motor and non-motor regions, within the frontal lobe, cerebellum, and basal ganglia, creating a functionally organized gradient. The contribution of secondary motor regions to working memory may be to generate internal motor traces that reinforce the representation of information held in mind. The primary aim of this review is to elucidate motor-cognitive interactions through the lens of working memory using the Sternberg paradigm as a model and to suggest origins of the motor-cognitive interface. In addition, we discuss the implications of the motor-cognitive relationship for clinical groups with motor network deficits. [ABSTRACT FROM AUTHOR]

The Supplementary Motor Area (SMA)-syndrome is a transient disturbance of the ability to initiate voluntary motor and speech actions that will often occur immediately after neurosurgical resections in the dorsal superior frontal gyrus but will typically have disappeared after 3 months. The purpose of the present study was to investigate the extent to which this syndrome is associated with alterations in cognitive control. Five patients who were to different extents affected by the SMA-syndrome after surgery for WHO grade II gliomas in the left hemisphere, were tested with the color word interference (Stroop) test; the Bergen dichotic listening test and for letter and category verbal fluency before surgery, 1–2 days after surgery and approximately 3 months after surgery. Results suggest that the motor symptoms known as the SMA syndrome co-occur with pronounced deficits in cognitive control. • Supplementary motor area (SMA) resections cause motor and speech deficits. • These effects seem to co-occur with pronounced deficits in cognitive control. • Motor, speech and cognitive deficits are restored 3 months after SMA-resections. • The SMA syndrome might be a disorder of executive functions. [ABSTRACT FROM AUTHOR]

Introduction: Several structural and functional neuroimaging studies have shown that the Supplementary Motor Area (SMA) is affected by tau pathology in patients with Progressive Supranuclear Palsy (PSP). The aim of the study was to investigate the biochemical profile of SMA in PSP patients, using proton magnetic resonance spectroscopy (1H-MRS).Methods: Sixteen PSP patients and 18 healthy controls participated in this study. 1H-MRS was performed by using a Point RESolving Spectroscopy (PRESS) single-voxel sequence implemented on a 3-T scanner. A voxel of 25 × 25 × 15 mm involving the right and left SMA was acquired in all subjects. Peak areas of N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (NAA), creatine with phosphocreatine (Cr), glycerophosphocholine + phosphocholine (Cho), glutamate + glutamine (Glx), glutathione (GSH), myo-Inositol (mI) and Scyllo-Inositol (Scyllo) were calculated using a version 6.3-1K of the fitting program LCModel. Comparative analysis was performed on both absolute concentrations and ratio values relative to Cr.Results: PSP patients showed a significant decrease in Scyllo concentration and Scyllo/Cr ratio values in SMA, compared to controls, whereas no difference between groups was found for the other ratio values. Of note, the attention and working memory functions were positively related to Scyllo and Scyllo/Cr values in PSP patients.Conclusions: Our study demonstrates that Scyllo and Scyllo/Cr were significantly reduced in the SMA of PSP patients. Because Scyllo seems to be able to protect against formation of toxic fibrils of amyloid-beta fragments and tau oligomers deposition, these preliminary findings may open new perspectives to investigate Scyllo as a new potential disease-modifying therapy for PSP. [ABSTRACT FROM AUTHOR]

Abstract Background Despite the prevalence of dual-task (e.g., walking while talking) deficits in people with multiple sclerosis (MS), no neuroimaging studies to date have examined neuronal networks used for dual-task processing or specific brain areas related to dual-task performance in this population. A better understanding of the relationship among underlying brain areas and dual-task performance may improve targeted rehabilitation programs. The objective of this study was to examine relationships between neuroimaging measures and clinical measures of dual-task performance, and reported falls in persons with MS. Materials and methods All participants completed measures of dual-task performance, a fall history, and neuroimaging on a 3 T MRI scanner. Spearman correlations were used to examine relationships among dual-task performance, falls and neuroimaging measures. Results Eighteen females with relapsing-remitting MS [mean age = 45.5 ± 8.2 SD; mean symptom duration = 12.3 ± 6.7 years; Expanded Disability Status Scale median 2.25 (range 1.5–4)] participated in this study. Structural imaging measures of supplementary motor area (SMA) interhemispheric connectivity were significantly related to dual-task walking variability. Conclusions The SMA interhemispheric tract may play a role in dual-task performance. Structural neuroimaging may be a useful adjunct to clinical measures to predict performance and provide information about recovery patterns in MS. Functional recovery can be challenging to objectively report in MS; diffusion tensor imaging could show microstructural improvements and suggest improved connectivity. Highlights • Difficulty performing two tasks at once (dual-tasking) is common in persons with MS. • Determining specific brain areas related to dual-tasking may improve rehabilitation. • We examined the relationship between MRI measures and dual-task performance.s • SMA interhemispheric tract was significantly related to dual-task walk variability. • SMA tract may play a role in dual-task performance. [ABSTRACT FROM AUTHOR]

Highlights • Developmental stuttering (DS) relies on dysfunctional neural exchange: the supplementary motor area (SMA) may play a key role. • We used combined TMS/EEG to investigate functional connectivity of the SMA "complex" in DS. • Abnormal neural timing in DS is inferred which helps to understand the pathophysiology of DS and develop new treatments. Abstract Objective Brain dynamics in developmental stuttering (DS) are not well understood. The supplementary motor area (SMA) plays a crucial role, since it communicates with regions related to planning/execution of movements, and with sub-cortical regions involved in paced/voluntary acts (such as speech). We used TMS combined with EEG to shed light on connections in DS, stimulating the SMA. Methods TMS/EEG was recorded in adult DS and fluent speakers (FS), stimulating the SMA during rest. TMS-evoked potentials and source distribution were evaluated. Results Compared to FS, stutterers showed lower activity of neural sources in early time windows: 66–82 ms in SMA, and 91–102 ms in the left inferior frontal cortex and left inferior parietal lobule. Stutterers, however, showed higher activations in later time windows (i.e. from 260–460 ms), in temporal/premotor regions of the right hemisphere. Conclusions These findings represent the functional counterpart to known white matter and cortico-basal-thalamo-cortical abnormalities in DS. They also explain how white matter abnormalities and cortico-basal-thalamo-cortical dysfunctions may be associated in DS. Finally, a mechanism is proposed in which compensatory activity of the non-dominant (right) hemisphere is recruited. Significance DS may be a disorder of neural timing that appears to be delayed compared to FS; new mechanisms that support stuttering symptoms are inferred; the SMA may be a promising target for neuro-rehabilitation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Left MPFC is correlated to motor symptoms of BSP. • Combined FCs of the left SMA can distinguish BSP patients from HCs. • Visual network modulates BSP. To explore the abnormalities of brain function in blepharospasm (BSP) and to illustrate its neural mechanisms by assuming supplementary motor area (SMA) as the entry point. Twenty-five patients with BSP and 23 controls underwent resting-state functional MRI, seed-based functional connectivity (FC), correlation analysis, receiver operating characteristic curve (ROC) analysis, and support vector machine (SVM) were applied to process the data. Patients showed that the left medial prefrontal cortex (MPFC), left lingual gyrus, right cerebellar crus I, and right lingual gyrus/cerebellar crus I had enhanced FC with the left SMA, whereas the right inferior temporal gyrus (ITG) had enhanced FC with the right SMA relative to controls. The FC between the left MPFC and left SMA was positively correlated with symptomatic severity. The ROC analysis verified that the abnormal FCs demonstrated in this study can separate patients and controls at high sensitivity and specificity. SVM analysis exhibited that combined FCs of the left SMA were optimal for distinguishing patients and control group at the accuracy of 89.58%, with sensitivity of 92.00% and specificity of 86.96%. Several brain networks partake in the neurobiology of BSP. SMA plays a vital role in several brain networks and might be the key pathogenic factor in BSP. Providing novel evidence for the engagement of the MPFC in the motor symptoms of BSP, enhancing credibility of the thesis that SMA regulates the neurobiology of BSP, and providing ideas of screening susceptible population of BSP using neuroimaging. [ABSTRACT FROM AUTHOR]

Recent fMRI findings revealed that impairment in a serial prediction task in patients suffering from Parkinson's disease (PD) results from hypoactivity of the SMA. Furthermore, hyperactivity of the lateral premotor cortex sustained performance after withdrawal of medication. To further explore these findings, we here examined the impact of deep brain stimulation of the subthalamic nucleus on the activity of the putamen and premotor areas while performing the serial prediction task. To this end, we measured eight male PD patients ON and OFF deep brain stimulation and eight healthy age-matched male controls using [ 15 O] water positron emission tomography to measure regional cerebral blood flow. As expected, PD patients showed poorer performance than healthy controls while performance did not differ between OFF and ON stimulation. Hypoactivity of the putamen and hyperactivity of the left lateral premotor cortex was found in patients compared to controls. Lateral premotor hyperactivity further increased OFF compared to ON stimulation and was positively related to task performance. These results confirm that the motor loop's dysfunction has impact on cognitive processes (here: prediction of serial stimuli) in PD. Extending prior data regarding the role of the lateral premotor cortex in cognitive compensation, our results indicate that lateral premotor cortex hyperactivity, while beneficial in moderate levels of impairment, might fail to preserve performance in more severe stages of the motor loop's degeneration. [ABSTRACT FROM AUTHOR]

Background A prime objective driving the recent development of human neural prosthetics is to stimulate neural circuits in a manner time-locked to ongoing brain activity. The human supplementary motor area (SMA) is a particularly useful target for this objective because it displays characteristic neural activity just prior to voluntary movement. Objective Here, we tested a method that detected activity in the human SMA related to impending movement and then delivered cortical stimulation with intracranial electrodes to influence the timing of movement. Methods We conducted experiments in nine patients with electrodes implanted for epilepsy localization: five patients with SMA electrodes and four control patients with electrodes outside the SMA. In the first experiment, electrocorticographic (ECoG) recordings were used to localize the electrode of interest during a task involving bimanual finger movements. In the second experiment, a real-time sense-and-stimulate (SAS) system was implemented that delivered an electrical stimulus when pre-movement gamma power exceeded a threshold. Results Stimulation based on real-time detection of this supra-threshold activity resulted in significant slowing of motor behavior in all of the cases where stimulation was carried out in the SMA patients but in none of the patients where stimulation was performed at the control site. Conclusions The neurophysiological correlates of impending movement can be used to trigger a closed loop stimulation device and influence ongoing motor behavior in a manner imperceptible to the subject. This is the first report of a human closed loop system designed to alter movement using direct cortical recordings and direct stimulation. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is characterized by biased information processing that leads to difficulties regulating negative affect, which includes difficulty decreasing negative affect as well as maladaptively increasing negative affect via cognitive processes. To examine the underlying neural correlates, we scanned depressed and never-depressed adults as they completed a cognitive reappraisal task which required decreasing negative affect while viewing a negative image (down-regulation) and increasing negative affect while viewing a neutral image (emotion generation). Compared to control participants, MDD participants had less recruitment of the dorsal anterior cingulate (dACC) and supplementary motor area (SMA) during early phases of down-regulation, the latter associated with poorer negative affect regulation. Further, MDD participants exhibited greater recruitment of the right middle temporal gyrus (MTG) during emotion generation, which was associated with lower negative affect. Dysregulated negative affect in MDD may be due to impairments in efficiently activating the dACC and SMA to meet regulation demands, and maladaptive generation of negative affect that characterizes individuals with MDD may be counteracted by compensatory activation in the MTG. Elucidating neural mechanisms that underlie the generation of negative affect in the absence of external stimuli is an important extension of previous work examining dysfunctional emotional processes in MDD. [ABSTRACT FROM AUTHOR]

Growing evidence implicates a decline in white matter integrity in the age-related decline in motor control. Functional neuroimaging studies show significant associations between functional connectivity in the cortical motor network, including the supplementary motor area (SMA), and motor performance. Dual-coil transcranial magnetic stimulation studies show facilitatory connections between SMA and the primary motor cortex (M1) in younger adults. Here, we investigated whether SMA-M1 facilitation is affected by age and whether the strength of SMA-M1 facilitation is associated with bilateral motor control. Dual-coil transcranial magnetic stimulation was used to measure SMA-M1 connectivity in younger (N = 20) and older adults (N = 18), and bilateral motor control was measured with the assembly subtest of the Purdue Pegboard and clinical measures of dynamic balance. SMA-M1 facilitation was seen in younger but not older adults, and a significant positive association was found between SMA-M1 facilitation and bimanual performance. These results show that SMA-M1 facilitation is reduced in older adults compared to younger adults and provide evidence of the functional importance of SMA-M1 facilitation. [ABSTRACT FROM AUTHOR]

Perception and action are inextricably linked, down to the level of single cells which have both visual and motor response properties – dubbed ‘mirror neurons’. The mirror neuron system is generally associated with direct-matching or resonance between observed and executed actions (and goals). Yet in everyday interactions responding to another's movements with matching actions (or goals) is not always appropriate. Here we examine processes associated with intentionally not imitating, as separable from merely detecting an observed action as mismatching one's own. Using fMRI, we test how matched and mismatched stimulus-response mapping for actions is modulated depending on task-relevance. Participants were either cued to intentionally copy or oppose a presented action (intentional imitation or counter-imitation), or cued to perform a predefined action regardless of the presented action (incidental imitation or counter-imitation). We found distinct cortical networks underlying imitation compared to counter-imitation, involving areas typically associated with an action observation network and widespread occipital activation. Intentionally counter-imitating particularly involved frontal-parietal networks, including the insula and cingulate cortices. This task-dependent recruitment of frontal networks for the intentional selection of opposing responses supports previous evidence for the preparatory suppression of imitative responses. Sensorimotor mirroring is modulated via control processes, which complex human interactions often require. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is used in a variety of disorders after stroke including upper limb motor dysfunctions, hemispatial neglect, aphasia, and apraxia, and its effectiveness has been demonstrated. Although gait ability is important for daily living, there were few reports of the use of tDCS to improve balance and gait ability. The supplementary motor area (SMA) was reported to play a potentially important role in balance recovery after stroke. We aimed to investigate the effect of combined therapy body weight-supported treadmill training (BWSTT) and tDCS on gait function recovery of stroke patients. Thirty stroke inpatients participated in this study. The two BWSTT periods of 1 weeks each, with real tDCS (anode: front of Cz, cathode: inion, 1 mA, 20 min) on SMA and sham stimulation, were randomized in a double-blind crossover design. We measured the time required for the 10 m Walk Test (10MWT) and Timed Up and Go (TUG) test before and after each period. We found that the real tDCS with BWSTT significantly improved gait speed (10MWT) and applicative walking ability (TUG), compared with BWSTT + sham stimulation periods (p < 0.05). Our findings demonstrated the feasibility and efficacy of tDCS in gait training after stroke. The facilitative effects of tDCS on SMA possibly improved postural control during BWSTT. The results indicated the implications for the use of tDCS in balance and gait training rehabilitation after stroke. [ABSTRACT FROM AUTHOR]

Background: A single low-dose ketamine infusion exhibited a rapid antidepressant effect within 1h. Despite its short biological half-life (approximately 3h), the antidepressant effect of ketamine has been demonstrated to persist for several days. However, changes in brain function responsible for the persistent antidepressant effect of a single low-dose ketamine infusion remain unclear METHODS: Twenty-four patients with treatment-resistant depression (TRD) were randomized into three groups according to the treatment received: 0.5mg/kg ketamine, 0.2mg/kg ketamine, and normal saline infusion. Standardized uptake values (SUVs) of glucose metabolism measured through 18F-FDG positron-emission-tomography before infusion and 1day after a 40-min ketamine or normal saline infusion were used for subsequent whole-brain voxel-wise analysis and were correlated with depressive symptoms, as defined using the Hamilton Depression Rating Scale-17 (HDRS-17) score RESULTS: The voxel-wise analysis revealed that patients with TRD receiving the 0.5mg/kg ketamine infusion had significantly higher SUVs (corrected for family-wise errors, P = 0.014) in the supplementary motor area (SMA) and dorsal anterior cingulate cortex (dACC) than did those receiving the 0.2mg/kg ketamine infusion. The increase in the SUV in the dACC was negatively correlated with depressive symptoms at 1day after ketamine infusion DISCUSSION: The persistent antidepressant effect of a 0.5mg/kg ketamine infusion may be mediated by increased activation in the SMA and dACC. The higher increase in dACC activation was related to the reduction in depressive symptoms after ketamine infusion. A 0.5mg/kg ketamine infusion facilitated the glutamatergic neurotransmission in the SMA and dACC, which may be responsible for the persistent antidepressant effect of ketamine much beyond its half-life. [ABSTRACT FROM AUTHOR]

Episodic memory involves the recollection of contextual details replayed mentally across time. Here, we propose the association-sequence network (ASN) model, characterizing complementary cortico-hippocampal networks underlying the retrieval of simultaneously associated and sequentially ordered events. Participants viewed objects, presented singly or in pairs, and later reported whether two objects were shown simultaneously, consecutively, or farther apart in time. Behavioral results and hippocampal activation reveal a correlation between the two sequential conditions but not the simultaneous condition, despite the temporal proximity of consecutive pairs. We also find that anterior hippocampal activity is modulated by temporal distance. Distinct cortical networks are engaged during simultaneous and sequential memory (prefrontal cortex and angular gyrus for association; supplementary motor cortex and precuneus for sequence); notably, these regions show differential connectivity with the hippocampus. The ASN model provides a comprehensive framework for how we reconstruct memories that are both rich in associative detail and temporally dynamic in nature. [Display omitted] • Hippocampal activity patterns differ for associative and temporal episodic memory • Dissociable cortical networks engage in recalling co-occurring and sequential items • The hippocampus selectively connects with these networks during memory retrieval • This may underlie the reconstruction of episodes that are both detailed and dynamic Episodic memory involves the recollection of both the contextual details and the temporal structure of an event. Here, Kim and Lee propose the association-sequence network (ASN) model of episodic memory, which posits that dissociable cortico-hippocampal networks underlie our mental reconstruction of simultaneously associated memory components and their temporal sequence. [ABSTRACT FROM AUTHOR]

Background The frontal aslant tract is a deep frontal pathway connecting the superior frontal gyrus (SFG) to Broca area. This fiber is assumed to be associated with language functions, especially speech initiation and spontaneity. The aim of this study was to electrophysiologically investigate this network using corticocortical evoked potentials (CCEPs). Methods This study enrolled 8 patients with brain tumors or medically intractable focal epilepsies who underwent frontal craniotomy over the language-dominant side. All patients underwent CCEP recordings during tumor resection or during invasive evaluation for epilepsy surgery. Alternating 1-Hz electrical stimuli were delivered to pars opercularis (pO) and pars triangularis (pT), corresponding to Broca area, and SFG via the subdural grid electrodes with intensity of 10 mA. Electrocorticograms from SFG and pO/pT time-locked to 50 stimuli were averaged in each trial to obtain CCEP responses. Results In all patients, stimulation of pO/pT induced CCEP responses in SFG. CCEP responses were recorded in lateral SFG in 5 patients and in supplementary motor areas in 4 patients. Reciprocality was observed in 7 patients in the stimulation of SFG. CCEP responses were significantly faster at SFG from pO/pT than at pO/pT from SFG (Wilcoxon signed rank test, P = 0.028). Conclusions The present study demonstrated a corticocortical network connecting Broca areas and SFG in a reciprocal manner. Our findings might provide new insight into language and motor integration. [ABSTRACT FROM AUTHOR]

Primary blepharospasm (BPS) is a focal dystonia characterized by involuntary eyelid spasms and blinking. The pathophysiology of BPS remains unclear. Several functional and structural neuroimaging studies have demonstrated abnormalities of sensorimotor structures such as the sensorimotor cortex, the basal ganglia, the thalamus and the cerebellum in BPS patients. However, some of the results of these studies were inconsistent. In addition, the relationship between the motor and sensory structures in patients with BPS still needs to be investigated. Therefore, the purpose of this study was to investigate the abnormal alterations in both the intra-regional brain activities and inter-regional functional connectivities (FC) in patients with BPS using resting-state functional MRI(rs-fMRI) and to explore possible correlations between these rs-fMRI indices and clinical variables. The rs-fMRI images of the two groups of subjects (26 BPS patients and 26 healthy controls) were acquired using a 3.0T MRI scanner. The regional rs-fMRI indices, i.e., the fractional amplitude of the low-frequency fluctuation (fALFF) and the regional homogeneity (ReHo), were computed for all subjects. Then, two-sample t -tests were conducted to assess the significant differences between the two groups of subjects. To investigate the alterations in brain networks, cerebral regions with significant differences were used as regions of interest in the whole brain FC analysis. Compared to the control group, the BPS patients revealed significantly increased fALFF and ReHo values in the right caudate head. Significantly strengthened FC values were observed between the right caudate head and the left striatum and the right supplementary motor area in the BPS group. The fALFF and ReHo values in the right caudate head and the FC values between the right caudate head and the left striatum were positively correlated with the Jankovic Rating Scale sum score. In conclusion, this study indicated that BPS patients have both abnormal intra-regional spontaneous brain activities and inter-regional functional connectivities. [ABSTRACT FROM AUTHOR]

Background Transcranial direct current stimulation (tDCS) can polarize the cortex of the human brain. Objective/Hypothesis We sought to verify the hypothesis that posterior-anterior (PA) but not anterior-posterior (AP) tDCS of primary motor cortex (M1) produces cooperative effects with corticospinal plasticity induced by paired associative stimulation of the supplementary motor area (SMA) to M1 projection (PAS SMA→M1 ) in a highly controlled experimental design. Methods Three experimental conditions were tested in a double-blinded, randomized crossover design in 15 healthy adults: Navigated PAS SMA→M1 during PA-tDCS (35 cm 2 electrodes, anode 3 cm posterior to M1 hand area, cathode over contralateral frontopolar cortex, 1 mA, 2 × 5 min) or AP-tDCS (reversed polarity), or sham-tDCS. Effects were analyzed over 120 min post-intervention by changes of motor evoked potential (MEP) amplitude in a hand muscle. Results There was no significant effect of tDCS on PAS SMA→M1 induced plasticity in the repeated-measures ANOVA. However, post-hoc within-subject contrasts revealed a significant tDCS with PAS SMA→M1 interaction. This was explained by PA-tDCS and AP-tDCS modifying the PAS SMA→M1 effect into the same direction in 13/15 subjects (87%, p = 0.004 for deviation from equality). Sizes of the PA-tDCS and AP-tDCS effects were correlated (r s = 0.53, p = 0.044). A control experiment demonstrated that PA-tDCS and AP-tDCS alone (without PAS SMA→M1 ) had no effect on MEP amplitude. Conclusions Data point to unidirectional tDCS effects on PAS SMA→M1 induced plasticity irrespective of tDCS polarity, in contrast to our hypothesis. We propose that radial symmetry of cortical columns, gyral geometry of motor cortex, and cooperativity of plasticity induction can explain the findings. [ABSTRACT FROM AUTHOR]

Obsessive-compulsive disorder (OCD) is a severely distressing disorder represented by obsessions and compulsions. A significant proportion of OCD patients fail to improve with conventional treatment methods. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as an alternative for OCD treatment. Functional neuroimaging studies indicate that OCD is associated with increased activity in the supplementary motor area (SMA), a region that plays an important role in the pathophysiology of this disorder. In this study, we assessed the efficacy of augmentation with 1 Hz rTMS over the SMA in treatment-resistant OCD patients. The participants received 1 Hz rTMS over the SMA in 20 daily sessions for 4 weeks. We observed significant reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score at the 4th week of the treatment. Reduction in compulsion contributed to the reduction of global Y-BOCS whereas there was no significant reduction in obsession. Clinical global impression-global improvement also showed significant change at the 2nd and 4th week of the treatment. No additional significant changes or significant adverse effects were seen. These findings suggest that 1 Hz rTMS over the SMA can be an efficient and safe add-on therapeutic method in treatment-resistant patients with OCD. Further controlled studies in larger samples are required to confirm the effect of 1 Hz rTMS over the SMA in OCD. [ABSTRACT FROM AUTHOR]

Several brain structures including the brainstem, the cerebellum and the frontal cortico-basal ganglia network, with the primary and premotor areas have been shown to participate in the functional organization of gait initiation and postural control in humans, but their respective roles remain poorly understood. The aim of this study was to better understand the role of the supplementary motor area (SMA) and posterior cerebellum in the gait initiation process. Gait initiation parameters were recorded in 22 controls both before and after continuous theta burst transcranial stimulation (cTBS) of the SMA and cerebellum, and were compared to sham stimulation, using a randomized double-blind design study. The two phases of gait initiation process were analyzed: anticipatory postural adjustments (APAs) and execution, with recordings of soleus and tibialis anterior muscles. Functional inhibition of the SMA led to a shortened APA phase duration with advanced and increased muscle activity; during execution, it also advanced muscle co-activation and decreased the duration of stance soleus activity. Cerebellar functional inhibition did not influence the APA phase duration and amplitude but increased muscle co-activation, it decreased execution duration and showed a trend to increase velocity, with increased swing soleus muscle duration and activity. The results suggest that the SMA contributes to both the timing and amplitude of the APAs with no influence on step execution and the posterior cerebellum in the coupling between the APAs and execution phases and leg muscle activity pattern during gait initiation. [ABSTRACT FROM AUTHOR]

The Supplementary Motor Area (SMA) is considered as an anatomically and functionally heterogeneous region and is implicated in several functions. We propose that SMA plays a crucial role in domain-general sequence processes, contributing to the integration of sequential elements into higher-order representations regardless of the nature of such elements (e.g., motor, temporal, spatial, numerical, linguistic, etc.). This review emphasizes the domain-general involvement of the SMA, as this region has been found to support sequence operations in a variety of cognitive domains that, albeit different, share an inherent sequence processing. These include action, time and spatial processing, numerical cognition, music and language processing, and working memory. In this light, we reviewed and synthesized recent neuroimaging, stimulation and electrophysiological studies in order to compare and reconcile the distinct sources of data by proposing a unifying account for the role of the SMA. We also discussed the differential contribution of the pre-SMA and SMA-proper in sequence operations, and possible neural mechanisms by which such operations are executed. [ABSTRACT FROM AUTHOR]

Objective To evaluate the microsurgical anatomy of the fiber tract connections of the supplementary motor area (SMA) and pre-SMA, and examine its potential functional role with reference to clinical trials in the literature. Methods Ten postmortem formalin-fixed human brains (20 sides) and 1 cadaveric head were prepared following Klingler's method. The fiber dissection was performed in a stepwise fashion, from lateral to medial and also from medial to lateral, under an operating microscope, with 3D images captured at each stage. Our findings were supported by in vivo magnetic resonance imaging tractography in 2 healthy subjects. Results The connections of the SMA complex, composed of the pre-SMA and the SMA proper, are composed of short “U” association fibers and the superior longitudinal fasciculus I, cingulum, claustrocortical fibers, callosal fibers, corticospinal tract, frontal aslant tract, and frontostriatal tract. The claustrocortical fibers may play an important role in the integration of motor, language, and limbic functions of the SMA complex. The frontostriatal tract connects the pre-SMA to the putamen and caudate nucleus, and also forms parts of both the internal capsule and the dorsal external capsule. Conclusions The SMA complex has numerous connections throughout the cerebrum. An understanding of these connections is important for presurgical planning for lesions in the frontal lobe and helps explain symptoms related to SMA injury. [ABSTRACT FROM AUTHOR]

Apart from its function in speech motor control, the supplementary motor area (SMA) has largely been neglected in models of speech and language processing in the brain. The aim of this review paper is to summarize more recent work, suggesting that the SMA has various superordinate control functions during speech communication and language reception, which is particularly relevant in case of increased task demands. The SMA is subdivided into a posterior region serving predominantly motor-related functions (SMA proper) whereas the anterior part (pre-SMA) is involved in higher-order cognitive control mechanisms. In analogy to motor triggering functions of the SMA proper, the pre-SMA seems to manage procedural aspects of cognitive processing. These latter functions, among others, comprise attentional switching, ambiguity resolution, context integration, and coordination between procedural and declarative memory structures. Regarding language processing, this refers, for example, to the use of inner speech mechanisms during language encoding, but also to lexical disambiguation, syntax and prosody integration, and context-tracking. [ABSTRACT FROM AUTHOR]

Attention Deficit Hyperactivity Disorder (ADHD) commonly affects children, although the symptoms persist into adulthood in approximately 50% of cases. Structural imaging studies in children have documented both cortical and subcortical changes in the brain. However, there have been only a few studies in adults and the results are inconclusive. Method Voxel-based morphometry (VBM) was applied to 44 adults with ADHD, Combined subtype, aged 18–54 years and 44 healthy controls matched for age, sex and IQ. Results ADHD patients showed reduced gray matter (GM) volume in the right supplementary motor area (SMA). Using more lenient thresholds we also observed reductions in the subgenual anterior cingulate (ACC) and right dorsolateral prefrontal (DLPFC) cortices and increases in the basal ganglia, specifically in the left caudate nucleus and putamen. There was a positive correlation between the cumulative stimulant dose and volume in the right SMA and DLPFC clusters. Conclusions The findings suggest that adults with ADHD show brain structural changes in regions belonging to the so-called cool executive function network. Long-term stimulant medication may act to normalize these GM alterations. [ABSTRACT FROM AUTHOR]

In patients with schizophrenia, obsessive-compulsive symptoms (OCS) are associated with lower rates of quality of life and polypharmacy. No previous controlled studies have tested the efficacy of repetitive transcranial magnetic stimulation (rTMS) on the treatment of OCS in this population. The present study examined the therapeutic effects of rTMS applied to the supplementary motor area (1 Hz, 20 min, 20 sessions) on OCS and general symptoms in patients with schizophrenia or schizoaffective disorder, and whether this intervention can produce changes in plasma levels of brain derived neurotrophic factor (BDNF). A double-blind randomized controlled trial was conducted. Active and sham rTMS were delivered to 12 patients (6 on each group). Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Brief Psychiatric Rating Scale (BPRS) scores, as well as BDNF levels, were assessed before, after, and 4 weeks after treatment. rTMS did not significantly change the outcomes after treatment and on the follow-up (Y-BOCS: Wald's X 2 =3.172; p =0.205; BPRS: X 2 =1.629; p =0.443; BDNF: X 2 =2.930; p =0.231). There seemed to be a trend towards improvement of BPRS scores 4 weeks after rTMS treatment comparing with sham (Cohen's d =0.875, with 32.9% statistical power). No side effects were reported. Future studies with larger sample sizes are needed. [ABSTRACT FROM AUTHOR]

Although the supplementary and pre-supplementary motor areas have been intensely investigated in relation to their motor functions, they are also consistently reported in studies of auditory processing and auditory imagery. This involvement is commonly overlooked, in contrast to lateral premotor and inferior prefrontal areas. We argue here for the engagement of supplementary motor areas across a variety of sound categories, including speech, vocalizations, and music, and we discuss how our understanding of auditory processes in these regions relate to findings and hypotheses from the motor literature. We suggest that supplementary and pre-supplementary motor areas play a role in facilitating spontaneous motor responses to sound, and in supporting a flexible engagement of sensorimotor processes to enable imagery and to guide auditory perception. [ABSTRACT FROM AUTHOR]

Background In a masked prime choice reaction task, presentation of a compatible prime increases the reaction time to the following imperative stimulus if the interval between mask and prime is around 80–250 ms. This is thought to be due to automatic suppression of the motor plan evoked by the prime, which delays reaction to the imperative stimulus. Oscillatory activity in motor networks around the beta frequency range of 20 Hz is important in suppression of movement. Transcranial alternating current at 20 Hz may be able to drive oscillations in the beta range. Objective/hypothesis To investigate whether transcranial alternating current stimulation (tACS) at 20 Hz would increase automatic inhibition in a masked prime task. As a control we used 10 Hz tACS. Methods Stimulation was delivered at alpha (10 Hz) and beta (20 Hz) frequency over the supplementary motor area and the primary motor cortex (simultaneous tACS of SMA-M1), which are part of the BG-cortical motor loop, during the execution of the subliminal masked prime left/right choice reaction task. We measured the effects on reaction times. Corticospinal excitability was assessed by measuring the amplitude of motor evoked potentials (MEPs) evoked in the first dorsal interosseous muscle by transcranial magnetic stimulation (TMS) over M1. Results The 10 and 20-Hz tACS over SMA-M1 had different effects on automatic inhibition. The 20 Hz tACS increased the duration of automatic inhibition whereas it was decreased by 10 Hz tACS. Neurophysiologically, 20 Hz tACS reduced the amplitude of MEPs evoked from M1, whereas there was no change after 10 Hz tACS. Conclusion Automatic mechanisms of motor inhibition can be modulated by tACS over motor areas of cortex. tACS may be a useful additional tool to investigate the causal links between endogenous brain oscillations and specific cognitive processes. [ABSTRACT FROM AUTHOR]

Background Brachial plexus injury (BPI) is a serious peripheral nerve injury, and clinical outcomes are generally unsatisfactory. It has been reported that cortical plasticity could influence the restoration of motor function. However, the neurologic mechanism of BPI is unclear, which provides a basis for further investigation. The supplementary motor area (SMA) plays an important role in the regulation of motor function. This study aims to explore SMA–whole brain functional connectivity after deafferentation of the brachial plexus. Methods Study subjects included 16 patients with BPI and 8 healthy volunteers. The seed region was defined by a block-design functional magnetic resonance imaging program that used unilateral imaginary hand grasp motion as a task stimulus. Next, the voxel–wise functional connectivity between the predefined region and the other regions of the brain was calculated. Results We discovered decreased voxel–wise functional connectivity between the SMA and multiple brain regions, including precuneus, posterior cingulum cortex, and anterior cingulum cortex, that are closely associated with information integration or motor processing in patients with BPI. Conclusions Patients with BPI showed weakened functional connectivity between hand grasp–related areas and the SMA and multiple regions associated with motor processing or information integration. A clear image of the functional status of the brain after deafferentation was provided. On the basis of this discovery, a relationship between changes in neuroimaging measurements and clinical outcomes can be determined in future studies. [ABSTRACT FROM AUTHOR]

Human bipedal balance control is achieved either reactively or predictively by a distributed network of neural areas within the central nervous system with a potential role for cerebral cortex. While the role of the cortex in reactive balance has been widely explored, only few studies have addressed the cortical activations related to predictive balance control. The present study investigated the cortical activations related to the preparation and execution of anticipatory postural adjustment (APA) that precede a step. This study also examined whether the preparatory cortical activations related to a specific movement is dependent on the context of control (postural component vs. focal component). Ground reaction forces and electroencephalographic (EEG) data were recorded from 14 healthy adults while they performed lateral weight shift and lateral stepping with and without initially preloading their weight to the stance leg. EEG analysis revealed that there were distinct movement-related potentials (MRPs) with concurrent event-related desynchronization (ERD) of mu and beta rhythms prior to the onset of APA and also to the onset of foot-off during lateral stepping in the fronto-central cortical areas. Also, the MRPs and ERD prior to the onset of APA and onset of lateral weight shift were not significantly different suggesting the comparable cortical activations for the generation of postural and focal movements. The present study reveals the occurrence of cortical activation prior to the execution of an APA that precedes a step. Importantly, this cortical activity appears independent of the context of the movement. [ABSTRACT FROM AUTHOR]

A fundamental prerequisite for goal-directed action is to encode the contingencies between responses (R) producing specific outcomes (O) in specific stimulus conditions (S). The present study aimed to characterize the functional neuroanatomy of different associational sub-components of such S–R–O contingencies during the first few trials of exposure. We devised a novel paradigm that was suited to distinguish BOLD activation patterns related to S–R, R–O, and the full S–R–O contingency. Different from previous studies our experimental design ensured that stimulus-related processes and outcome-related processes were maximally comparable, as both were learned incidentally and lacked intrinsic incentive value, and different from trial-and-error learning situations, outcomes did not serve a special role as performance feedback. We observed contingency-related dissociations between SMA, lateral OFC, and large parts of the reward system including central OFC, anterior striatum and midbrain areas. While the lateral OFC was involved in processing differential outcomes irrespective of a predictive stimulus context, the SMA was specifically engaged when differential outcomes could be predicted by the stimulus. By contrast, the activation pattern of reward system areas suggested that these regions serve a role in integrating non-incentive differential outcome information and incentive common outcome information. Together, these results support the notion that striatal and orbitofrontal regions are involved in outcome-related processes beyond trial-and-error S–R learning, that is, when outcomes are non-incentive and do not serve as reinforcing feedback that drives learning. Furthermore, our results clarify the role of the SMA in outcome-related processes thereby supporting current versions of ideomotor theory. [ABSTRACT FROM AUTHOR]