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The role of motor activity ipsilateral to movement remains a matter of debate, due in part to discrepancies among studies in the localization of this activity, when observed, and uncertainty about its time course. The present study used magnetoencephalography (MEG) to investigate the spatial localization and temporal dynamics of contralateral and ipsilateral motor activity during the preparation of unilateral finger movements. Eight right-handed normal subjects carried out self-paced finger-lifting movements with either their dominant or nondominant hand during MEG recordings. The Multi-Start Spatial Temporal multi-dipole method was used to analyze MEG responses recorded during the movement preparation and early execution stage (-800 msec to +30 msec) of movement. Three sources were localized consistently, including a source in the contralateral primary motor area (M1) and in the supplementary motor area (SMA). A third source ipsilateral to movement was located significantly anterior, inferior, and lateral to M1, in the premotor area (PMA) (Brodmann area [BA] 6). Peak latency of the SMA and the ipsilateral PMA sources significantly preceded the peak latency of the contralateral M1 source by 60 msec and 52 msec, respectively. Peak dipole strengths of both the SMA and ipsilateral PMA sources were significantly weaker than was the contralateral M1 source, but did not differ from each other. Altogether, the results indicated that the ipsilateral motor activity was associated with premotor function, rather than activity in M1. The time courses of activation in SMA and ipsilateral PMA were consistent with their purported roles in planning movements.

Motor behavior and sensorimotor activation of the cerebrum and cerebellum were measured before and after motor imagery-based mental practice (MP) and physical practice (PP) of a sequential motor task. Two-button-press sequences (A, B) were performed outside a magnetic resonance imaging scanner and at 2 Hz inside the scanner during a pretest. Participants (n = 39) completed PP, MP, or no practice (NP) of Sequence A for 1 week and were posttested. Sequence A performance improved 121%, 86%, and 4% for the PP, MP, and NP groups, respectively (p < 0.05), while Sequence B improved 56%, 40%, and 38% (p > 0.05). PP improvements were accompanied by increased striatal and decreased cerebellar activation, while MP improvements were accompanied by increased cerebellar, premotor, and striatal activation. The efficacy of MP for activating cerebral and cerebellar sensorimotor networks suggests that MP might be an effective substitute or complement to PP to activate compensatory networks for motor rehabilitation.

Objectives: Individuals with bipolar disorder (BPD) exhibit motor, perceptual, and cognitive disturbances involving predominantly right hemisphere dysfunction. This asymmetry has been used to advance the hypothesis that the pathogenesis of bipolar disorder may be related to disturbances of the right cerebral hemisphere. We employed functional magnetic resonance imaging to examine hemispheric asymmetries in manic and depressed BPD. A secondary goal of the Study was to examine effects of psychotropic medications on blood Volume changes in the motor cortices. Methods: We studied 18 right-handed BPD and 13 right-handed normal healthy comparison subjects. Blood oxygen level dependent (BOLD) responses in the primary motor area (M1) and Supplementary motor area (SMA) of both hemispheres were elicited during reaction time (RT) tasks. Results: Healthy subjects activated the SMA in a reciprocal fashion with significantly greater activity in the left SMA for right hand trials and the right SMA for left hand trials. Depressed BPD subjects failed to show this normal reciprocity indicating a failure to Suppress unwanted activity in the ipsilateral right SMA, whereas manic BPD subjects failed to suppress unwanted ipsilateral SMA activity in both hemispheres. Manic and depressed BPD subjects exhibited greater activity in the left primary motor area suggesting increased cortical excitability. BPD subjects treated with antipsychotics or mood-stabilizing medications exhibited longer RTs, lower BOLD responses in M1 and SMA, and a loss of normal hemispheric asymmetry in the SMA than untreated subjects. Conclusions: The presence of a right hemisphere disturbance in BPD is consistent with the hypothesis that the right hemisphere may be dominant in mood regulation. The presence of both left and right hemisphere disturbances in mania may explain the coexisting psychotic and affective symptoms observed in this condition.

Aims: The relationship between freezing of gait (FOG) and regional brain atrophy has been intensively investigated, but it is still not clearly understood. The study objective was to test whether grey matter (GM) atrophy contributes to FOG in Parkinson's disease (PD) using a surface-based algorithm. Methods: We investigated 21 patients with PD, 11 with FOG and 10 without FOG. Both groups were assessed using a FOG questionnaire and Hoehn and Yahr staging. High resolution T1-weighted brain images were acquired for each subject using a 1.5T MRI scanner. A surface-based method implemented in FreeSurfer was used to quantify the GM atrophy. A vertex-wise and region of interest (ROI) comparison of spatially normalized subject data using a general linear model and the Wilcoxon rank sum test were to assess significant group differences. Results: Higher global levels of cortical atrophy were detected in freezers, although this was not statistically significant. The vertex-wise analysis revealed significant local reduction in grey matter thickness in the left supplementary motor area, middle/anterior cingulate cortex, temporal pole and right frontal operculum in freezers at P

Background and Purpose: The human supplementary motor area (SMA) contains two functional subregions of the SMA proper and preSMA; however, the reorganization patterns of the two SMA subregions after stroke remain uncertain. Meanwhile, a focal subcortical lesion may affect the overall functional reorganization of brain networks. We sought to identify the differential reorganization of the SMA subregions after subcortical stroke using the resting-state functional connectivity (rsFC) analysis.Methods: Resting-state functional MRI was conducted in 25 patients with chronic capsular stroke exhibiting well-recovered global motor function (Fugl–Meyer score >90). The SMA proper and preSMA were identified by the rsFC-based parcellation, and the rsFCs of each SMA subregion were compared between stroke patients and healthy controls.Results: Despite common rsFC with the fronto-insular cortex (FIC), the SMA proper and preSMA were mainly correlated with the sensorimotor areas and cognitive-related regions, respectively. In stroke patients, the SMA proper and preSMA exhibited completely different functional reorganization patterns: the former showed increased rsFCs with the primary sensorimotor area and caudal cingulate motor area (CMA) of the motor execution network, whereas the latter showed increased rsFC with the rostral CMA of the motor control network. Both of the two SMA subregions showed decreased rsFC with the FIC in stroke patients; the preSMA additionally showed decreased rsFC with the prefrontal cortex (PFC).Conclusion: Although both SMA subregions exhibit functional disconnection with the cognitive-related areas, the SMA proper is implicated in the functional reorganization within the motor execution network, whereas the preSMA is involved in the functional reorganization within the motor control network in stroke patients.

We previously created a prosthetic hand with a tacit learning system (TLS) that automatically supports the control of forearm pronosupination. This myoelectric prosthetic hand enables sensory feedback and flexible motor output, which allows users to move efficiently with minimal burden. In this study, we investigated whether electroencephalography can be used to analyze the influence of the auxiliary function of the TLS on brain function. Three male participants who had sustained below-elbow amputations and were myoelectric prosthesis users performed a series of physical movement trials with the TLS inactivated and activated. Trials were video recorded and a sequence of videos was prepared to represent each individual’s own use while the system was inactivated and activated. In a subsequent motor imagery phase during which electroencephalography (EEG) signals were collected, each participant was asked to watch both videos of themself while actively imagining the physical movement depicted. Differences in mean cortical current and amplitude envelope correlation (AEC) values between supplementary motor areas (SMA) and each vertex were calculated. For all participants, there were differences in the mean cortical current generated by the motor imagery tasks when the TLS inactivated and activated conditions were compared. The AEC values were higher during the movement imagery task with TLS activation, although their distribution on the cortex varied between the three individuals. In both S1 and other brain areas, AEC values increased in conditions with the TLS activated. Evidence from this case series indicates that, in addition to motor control, TLS may change sensory stimulus recognition.

Background: Altered functional connectivity (FC) is related to pathophysiology of patients with cervical dystonia (CD). However, inconsistent results may be obtained due to different selected regions of interest. We explored voxel-wise brain-wide FC changes in patients with CD at rest in an unbiased manner and analyzed their correlations with symptomatic severity using the Tsui scale.Method: A total of 19 patients with CD and 21 sex- and age-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. Global-brain FC (GFC) was applied to analyze the images. Support vector machine was used to distinguish the patients from the controls.Results: Patients with CD exhibited decreased GFC in the right precentral gyrus and right supplementary motor area (SMA) that belonged to the M1-SMA motor network. Significantly negative correlation was observed between GFC values in the right precentral gyrus and symptomatic severity in the patients (r = −0.476, p = 0.039, uncorrected). Decreased GFC values in these two brain regions could be utilized to differentiate the patients from the controls with good accuracies, sensitivities and specificities (83.33, 85.71, and 80.95% in the right precentral gyrus; and 87.59, 89.49, and 85.71% in the right SMA).Conclusions: Our investigation suggests that patients with CD show reduced GFC in brain regions of the M1-SMA motor network and provides further insights into the pathophysiology of CD. GFC values in the right precentral gyrus and right SMA may be used as potential biomarkers to recognize the patients from the controls.

Specific impairments of anticipatory postural adjustment (APA) during step initiation have been reported in patients with Parkinson’s disease (PD) and freezing of gait (FoG). Although APA disruption has been associated with FoG, there is scarce knowledge about its neural correlates. We sought to better understand the neural networks involved with APA in patients with FoG by assessing the level of hemodynamic response of specific brain regions and the functional connectivity during the leg lifting task. In the current investigation, APAs of patients with PD, with and without (nFoG) freezing were assessed during a leg lifting task in an event-related, functional magnetic resonance imaging (er-fMRI) protocol. Results identified a high hemodynamic response in the right anterior insula (AI) and supplementary motor area (SMA) in the FoG group when an APA was required. The nFoG had stronger connectivity between the right and left insulae than the FoG group. The strength of this connectivity was negatively correlated with the severity of FoG. Both groups showed different brain network organizations comprising the SMA and the bilateral AI. The SMA was found to be a hub in patients with FoG when an APA was required for the task. Our findings suggest that both groups used compensatory mechanism comprising the insulae during APA. Neither group used the entire network comprised of the insulae and SMA to accomplish the task. The FoG group relied more on SMA as a hub than as part of a broader network to exchange information during the APA.

Primate studies indicate that the pyramidal tract (PyT) could originate from Brodmann area (BA) 6. However, in humans, the accurate origin of PyT from BA 6 is still uncertain owing to difficulties in visualizing anatomical features such as the fanning shape at the corona radiata and multiple crossings at the semioval centrum. High angular-resolution diffusion imaging (HARDI) could reliably replicate these anatomical features. We explored the origin of the human PyT from BA 6 using HARDI. With HARDI data of 30 adults from the Massachusetts General Hospital-Human Connectome Project (MGH-HCP) database and the HCP 1021 template (average of 1021 HCP diffusion data), we visualized the PyT at the 30-averaged group level and the 1021 large-sample level and validated the observations in each of the individuals. Endpoints of the fibers within each subregion were quantified. PyT fibers originating from the BA 6 were consistently visualized in all images. Specifically, the bilateral supplementary motor area (SMA) and dorsal premotor area (dPMA) were consistently found to contribute to the PyT. PyT fibers from BA 6 and those from BA 4 exhibited a twisting topology. The PyT contains fibers originating from the SMA and dPMA in BA 6. Infarction of these regions or aging would result in incomplete provision of information to the PyT and concomitant decreases in motor planning and coordination abilities.

The study of motor timing informs on how temporal information integrates with motor acts. Cortico-basal ganglia and cortico-cerebellar circuits control this integration, whereas transcallosal interhemispheric connectivity modulates finely timed lateralized or bimanual actions. Motor timing abilities are under-explored in Tourette syndrome (TS). We adopted a synchronization-continuation task to investigate motor timing in sequential movements in TS patients. We studied 14 adult TS patients and 19 age-matched healthy volunteers. They were asked to tap in synchrony with a metronome cue (SYNC) and then, when the tone stopped, to keep tapping, maintaining the same rhythm (CONT). We tested both a sub-second and a supra-second inter-stimulus interval between the cues. Subjects randomly performed a single-hand task with the right hand and a bimanual task using both hands simultaneously wearing sensor-engineered gloves. We measured the temporal error and the interval reproduction accuracy index. We also performed MRI-based diffusion tensor imaging and probabilistic tractography of inter-hemispheric corpus callosum (CC) connections between supplementary motor areas (SMA) and the left SMA-putamen fiber tract. TS patients were less accurate than healthy individuals only on the single-hand version of the CONT task when asked to reproduce supra-second time interval. Supra-second time processing improved in TS patients in the bimanual task, with the performance of the right hand on the bimanual version of the CONT task being more accurate than that of the right hand on the single-hand version of the task. We detected a significantly higher fractional anisotropy (FA) in both SMA-SMA callosal and left-sided SMA-putamen fiber tracts in TS patients. In TS patients only, the structural organization of transcallosal connections between the SMAs and of the left SMA-putamen tract was higher when the motor timing accuracy of the right hand on the bimanual version of the task was lower. Abnormal timing performance for supra-second time processing is suggestive of a defective network inter-connecting the striatum, the dorsolateral prefrontal cortex and the SMA. An increase in accuracy on the bimanual version of the CONT task may be the result of compensatory processes linked to self-regulation of motor control, as witnessed by plastic rearrangement of inter-hemispheric and cortical-subcortical fiber tracts.

Background: The combination of transcranial direct current stimulation (tDCS) with balance training could integrate central and peripheral neural mechanisms. This study aimed to investigate the effects of concurrent balance training and tDCS over the supplementary motor area (SMA) on anticipatory postural adjustments during gait initiation (GI) in persons with chronic ankle instability (CAI)., Hypothesis: Balance training will increase the center of pressure (COP) velocity and displacement during GI phases in all participants, and those receiving real tDCS will show greater increases., Study Design: Randomized controlled trial., Level of Evidence: Level 2., Methods: A total of 32 subjects were allocated to 2 groups: (1) intervention (balance training plus real tDCS) and (2) control (balance training plus sham tDCS). Outcome measures were COP-related parameters (displacement and velocity) during phases of GI (anticipatory, weight transition, and locomotor)., Results: The results showed that, in the anticipatory phase, the anteroposterior displacement of the COP was increased significantly at posttest relative to pretest across both groups, F (1,30) = 5.733, P = 0.02. In addition, both groups revealed an increase in the mediolateral COP velocity at posttest, F (1,30) = 10.523, P < 0.01. In the weight transition phase, both groups had higher mediolateral COP velocity at posttest, F (1,30) = 30.636, P < 0.01. In the locomotor phase, in both groups, the anteroposterior COP velocity was increased significantly at posttest compared with pretest, F (1,30) = 5.883, P = 0.02., Conclusion: Both groups demonstrated improvements in the anticipatory and execution phases of GI. Since no between-group difference was found, it can be interpreted that the anodal tDCS applied over the SMA has no added value over sham stimulation., Clinical Relevance: Balance training is beneficial for persons with CAI and can improve the anticipation and execution phases of GI without the aid of brain stimulation., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.

Background and Purpose : The human supplementary motor area (SMA) contains two functional subregions of the SMA proper and preSMA; however, the reorganization patterns of the two SMA subregions after stroke remain uncertain. Meanwhile, a focal subcortical lesion may affect the overall functional reorganization of brain networks. We sought to identify the differential reorganization of the SMA subregions after subcortical stroke using the resting-state functional connectivity (rsFC) analysis. Methods : Resting-state functional MRI was conducted in 25 patients with chronic capsular stroke exhibiting well-recovered global motor function (Fugl–Meyer score >90). The SMA proper and preSMA were identified by the rsFC-based parcellation, and the rsFCs of each SMA subregion were compared between stroke patients and healthy controls. Results : Despite common rsFC with the fronto-insular cortex (FIC), the SMA proper and preSMA were mainly correlated with the sensorimotor areas and cognitive-related regions, respectively. In stroke patients, the SMA proper and preSMA exhibited completely different functional reorganization patterns: the former showed increased rsFCs with the primary sensorimotor area and caudal cingulate motor area (CMA) of the motor execution network, whereas the latter showed increased rsFC with the rostral CMA of the motor control network. Both of the two SMA subregions showed decreased rsFC with the FIC in stroke patients; the preSMA additionally showed decreased rsFC with the prefrontal cortex (PFC). Conclusion : Although both SMA subregions exhibit functional disconnection with the cognitive-related areas, the SMA proper is implicated in the functional reorganization within the motor execution network, whereas the preSMA is involved in the functional reorganization within the motor control network in stroke patients. [ABSTRACT FROM AUTHOR]

Background: The postoperative supplementary motor area (SMA) syndrome may complicate unilateral surgery involving the SMA cortex and manifests as contralateral or global akinesia, mutism, or speech deficit, with complete or major recovery in weeks to months. Case series: We observed retrospectively nine patients (median age 47 years, range 27-60, five female) who underwent surgery for left premotor area tumors (six intra-axial and three extra-axial). Volumetric microsurgical resection was performed with neuro-navigational assistance (Vector Vision-BrainLab™ or SonoWand Invite™). We achieved gross or near gross total resection in all cases. The patients were followed clinically for one year, with control computed tomography scan within 24-48 hours from the operation and control magnetic resonance imaging three months and one year postoperatively. Five patients had only akinesia of the contralateral limbs, two had akinesia and mutism, and the remaining two had mutism only. All recovered within three months. The severity and duration were related to the location of resection rather than the volume removed. Cortical excision closer to the premotor area was related to more prominent SMA syndrome, while the cingular gyrus' involvement related to mutism. Conclusion: Prevention of SMA syndrome is not always possible in resective surgery. Given its favorable prognosis, it should be well known to the health professionals of different specialties engaged in such patients' postoperative care. The possibility of SMA should be preoperatively discussed with the patients and caregivers. [ABSTRACT FROM AUTHOR]

The supplementary motor area (SMA) syndrome is characterized by transient weakness and akinesia contralateral to the side of the affected hemisphere. The underlying pathology of the syndrome is not fully understood but is thought to be related to lesions in the SMA, residing principally in the mesial superior frontal gyrus (Broadmann's area 6c). Although the SMA syndrome a well-characterized clinical entity, we report herein, to our knowledge, the first case of isolated lower extremity SMA syndrome in the literature. This case highlights the importance of considering this rare clinical entity in the context of new or worsening postoperative neurologic deficits. Moreover, early studies did not support somatotopic organization of the SMA as in the primary motor cortex; emerging evidence suggests that delicate somatotopic representation may underlie distinct presentations like that reported in the present case. [ABSTRACT FROM AUTHOR]

Psychomotor slowing is frequently distressing patients with depression and schizophrenia. Increased neural activity within premotor cortices is linked to psychomotor slowing. This transdiagnostic study tested whether add-on inhibitory repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area (SMA) may alleviate psychomotor slowing. Forty-five patients with severe psychomotor slowing (26 psychosis, 19 major depression) were randomized in this transdiagnostic, double-blind, parallel-group, sham-controlled trial of 15 daily sessions of add-on rTMS over 3 weeks. Treatment arms included inhibitory 1 Hz stimulation of the SMA, facilitatory intermittent theta burst stimulation (iTBS) of the SMA, facilitatory 15 Hz stimulation of the left dorsolateral prefrontal cortex (DLPFC), and sham stimulation of the occipital cortex. The primary outcome was response (>30% reduction from baseline) according to the Salpêtrière Retardation Rating Scale (SRRS). Secondary outcomes were course of SRRS and further symptom rating scales. Last-observation carried forward method was applied to all subjects with baseline data. Response rates differed between protocols: 82% with inhibitory 1 Hz rTMS of the SMA, 0% with facilitatory iTBS of the SMA, 30% with sham, and 33% with 15 Hz DLPFC rTMS (χ² = 16.6, P < .001). Dropouts were similarly distributed across protocols. Response rates were similar in the completer analysis. This transdiagnostic trial of rTMS demonstrates that inhibitory SMA stimulation may ameliorate psychomotor slowing in severely ill patients. It further provides proof-of-concept that motor inhibition is linked to increased neural activity in the SMA because the inhibitory protocol performed best in reducing symptoms. Trial registration: NCT03275766 (www.clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Deficits in proprioception, the ability to discriminate the relative position and movement of our limbs, affect ~50% of stroke patients and reduce functional outcomes. Our lack of knowledge of the anatomical correlates of proprioceptive processing limits our understanding of the impact that such deficits have on recovery. This research investigated the relationship between functional impairment in brain activity and proprioception post-stroke. We developed a novel device and task for arm position matching during functional MRI (fMRI), and investigated 16 subjects with recent stroke and nine healthy age-matched controls. The stroke-affected arm was moved by an experimenter (passive arm), and subjects were required to match the position of this limb with the opposite arm (active arm). Brain activity during passive and active arm movements was determined, as well as activity in association with performance error. Passive arm movement in healthy controls was associated with activity in contralateral primary somatosensory (SI) and motor cortices (MI), bilateral parietal cortex, supplementary (SMA) and premotor cortices, secondary somatosensory cortices (SII), and putamen. Active arm matching was associated with activity in contralateral SI, MI, bilateral SMA, premotor cortex, putamen, and ipsilateral cerebellum. In subjects with stroke, similar patterns of activity were observed. However, in stroke subjects, greater proprioceptive error was associated with less activity in ipsilesional supramarginal and superior temporal gyri, and lateral thalamus. During active arm movement, greater proprioceptive error was associated with less activity in bilateral SMA and ipsilesional premotor cortex. Our results enhance our understanding of the correlates of proprioception within the temporal parietal cortex and supplementary/premotor cortices. These findings also offer potential targets for therapeutic intervention to improve proprioception in recovering stroke patients and thus improve functional outcome. [ABSTRACT FROM AUTHOR]

Objective: Multispectrum electrocorticographic components are critical for mapping the nonprimary motor area (NPMA). The objective of this study was to derive and validate a reliable scoring system for electrocorticography‐based NPMA mapping (NPMA score) to replace electrical cortical stimulation (ECS) during brain surgery. Methods: We analyzed 14 consecutive epilepsy patients with subdural electrodes implanted in the frontal lobe at Kyoto University Hospital. The NPMA score was retrospectively derived from multivariate analysis in the derivation group (patients = 7, electrodes = 713, during 2010‐2013) and validated in the validation group (patients = 7, electrodes = 772, during 2014‐2017). We assessed the accuracy and reliability of the score relative to ECS in determining the NPMA and predicting postoperative functional outcomes. Results: Multivariate analysis in the derivation group led to an 8‐point score for predicting ECS‐based NPMA (1 point for anatomical localization of the electrode and 1 or 2 points for movement‐related electrocorticographic components regardless of somatotopy in very slow cortical potential shifts [<0.5 Hz], 40‐80–Hz band power increase, and 8‐24–Hz band power decrease), which was validated in the validation group. The area under the receiver operating characteristic curve (AUC) was 0.89 in the derivation group. Good prediction (specificity = 94%, sensitivity = 100%) and discrimination (AUC = 0.87) were reproduced in the validation group. Overall, higher NPMA scores identified 2 patients with postoperative deficits after frontal lobe resection. Significance: The NPMA score is reliable for NPMA mapping, potentially replacing ECS. It is a potential prognostic marker for postoperative functional deficits. [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]

Primate studies indicate that the pyramidal tract (PyT) could originate from Brodmann area (BA) 6. However, in humans, the accurate origin of PyT from BA 6 is still uncertain owing to difficulties in visualizing anatomical features such as the fanning shape at the corona radiata and multiple crossings at the semioval centrum. High angular-resolution diffusion imaging (HARDI) could reliably replicate these anatomical features. We explored the origin of the human PyT from BA 6 using HARDI. With HARDI data of 30 adults from the Massachusetts General Hospital-Human Connectome Project (MGH-HCP) database and the HCP 1021 template (average of 1021 HCP diffusion data), we visualized the PyT at the 30-averaged group level and the 1021 large-sample level and validated the observations in each of the individuals. Endpoints of the fibers within each subregion were quantified. PyT fibers originating from the BA 6 were consistently visualized in all images. Specifically, the bilateral supplementary motor area (SMA) and dorsal premotor area (dPMA) were consistently found to contribute to the PyT. PyT fibers from BA 6 and those from BA 4 exhibited a twisting topology. The PyT contains fibers originating from the SMA and dPMA in BA 6. Infarction of these regions or aging would result in incomplete provision of information to the PyT and concomitant decreases in motor planning and coordination abilities. [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]

Aims: In the human brain, supplementary motor area (SMA) is involved in the control of pelvic floor muscles (PFMs). SMA dysfunction has been implicated in several disorders involving PFMs, including urinary incontinence and urologic pain. Here, we aimed to provide a proof‐of‐concept study to demonstrate the feasibility of modulating resting PFM activity (tone) as well as SMA activity with noninvasive stimulation of SMA. Methods: We studied six patients (3 women + 3 men) with Urologic Chronic Pelvic Pain Syndrome. Repetitive transcranial magnetic stimulation (rTMS) was applied to SMA immediately after voiding. We tested two rTMS protocols: high‐frequency (HF‐rTMS) which is generally excitatory, and low‐frequency (LF‐rTMS) which is generally inhibitory. PFM activity was measured during rTMS using electromyography. Brain activity was measured immediately before and after rTMS using functional magnetic resonance imaging. Results: The rTMS protocols had significantly different effects on resting activity in PFMs (P = 0.03): HF‐rTMS decreased and LF‐rTMS increased pelvic floor tone. SMA activity showed a clear trend (P = 0.06) toward the expected differential changes: HF‐rTMS increased and LF‐rTMS decreased SMA activity. Conclusions: We interpret the differential effects of rTMS at the brain and muscle level as novel support for an important inhibitory influence of SMA activity on pelvic floor tone after voiding. This preliminary study provides a framework for designing future studies to determine if neuromodulation of SMA could augment therapy for chronic urologic conditions. [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]

The execution of coordinated hand movements requires complex interactions between premotor and primary motor areas in the two hemispheres. The supplementary motor area (SMA) is involved in movement preparation and bimanual coordination. How the SMA controls bimanual coordination remains unclear, although there is evidence suggesting that the SMA could modulate interhemispheric interactions. With a delayed‐response task, we investigated interhemispheric interactions underlying normal movement preparation and the role of the SMA in these interactions during the delay period of unimanual or bimanual hand movements. We used functional MRI and transcranial magnetic stimulation in 22 healthy volunteers (HVs), and then in two models of SMA dysfunction: (a) in the same group of HVs after transient disruption of the right SMA proper by continuous transcranial magnetic theta‐burst stimulation; (b) in a group of 22 patients with congenital mirror movements (CMM), whose inability to produce asymmetric hand movements is associated with SMA dysfunction. In HVs, interhemispheric connectivity during the delay period was modulated according to whether or not hand coordination was required for the forthcoming movement. In HVs following SMA disruption and in CMM patients, interhemispheric connectivity was modified during the delay period and the interhemispheric inhibition was decreased. Using two models of SMA dysfunction, we showed that the SMA modulates interhemispheric interactions during movement preparation. This unveils a new role for the SMA and highlights its importance in coordinated movement preparation. [ABSTRACT FROM AUTHOR]

Gelastic seizure (GS) is a cardinal symptom of hypothalamic hamartoma (HH), which is intractable but surgically remediable. Although facial asymmetry with GS has not been extensively discussed, asymmetric GS has been frequently recognized in our large series. We hypothesized that asymmetric GS represents a lateralizing sign caused by the epileptic propagation from the attachment of the HH. To examine this hypothesis, the positive predictive value (PPV) and diagnostic odds ratio (DOR) of asymmetric GS were validated to predict the side of HH attachment. In 103 cases registered to the present analysis, asymmetric GS was recognized in 71 patients and symmetric GS in 32. Asymmetric GS with a lopsided grimace was exclusively observed on the side contralateral to unilateral HH in 39 patients and to the dominant attachment of 23 HHs with bilateral attachment (true positive, n = 62). In contrast, asymmetric GS was exhibited independently on both sides in 4 patients with bilaterally attached HH and on the side ipsilateral to the dominant attachment in the other 4. Symmetric HH attachments were identified in 1 patient (false negative, n = 9). Asymmetric GS was a reliable lateralizing sign with high DOR (6.08) and PPV (78%) to predict the side of epileptic propagation. Furthermore, the present study demonstrated the probability of seizure propagation from bilateral attachment, and this evidence provides a new rationale to the surgical strategy of bilateral disconnection for HH with bilateral attachment. • Asymmetric gelastic seizure is a new lateralizing sign with high predictive value. • This sign predicts the side contralateral to the hamartoma attachment. • Such asymmetry is attributed to intrahemispheric propagation from the hamartoma. • Bilateral attachment may increase the probability of bilateral seizure propagation. • We discussed the rationale of bilateral hamartoma disconnection. [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 The supplementary motor area (SMA) has been shown to be involved in interval timing but its precise role remains a matter of debate. The present study was aimed at examining, by means of intracerebral EEG recordings, the time course of the activity in this structure, as well as in other functionally connected cortical (frontal, cingulate, insular and temporal) areas, during a visual time reproduction task. Four patients undergoing stereo-electroencephalography (SEEG) for presurgical investigation of refractory focal epilepsy were enrolled. They were selected on the presence of depth electrodes implanted within the SMA. They were instructed to encode, keep in memory and then reproduce the duration (3, 5 and 7 s) of emotionally-neutral or negative pictures. Emotional stimuli were used with the aim of examining neural correlates of temporal distortions induced by emotion. Event-related potentials (ERPs) were analyzed during three periods: During and at the extinction of the target interval (TI) and at the beginning of the reproduction interval (RI). Electrophysiological data revealed an ERP time-locked to TI-offset whose amplitude varied monotonically with TI-duration. This effect was observed in three out of the four patients, especially within the SMA and the insula. It also involved the middle and anterior cingulate cortex, the superior, middle and inferior frontal gyri and the paracentral lobule. These effects were modulated by the prior TI-duration and predicted variations in temporal reproduction accuracy. In contrast, modulations of ERPs with TI-duration, emotion or temporal performance during the target or the reproduction interval were modest and less consistent across patients. These results demonstrate that, during reproduction of supra-second time intervals, the SMA, in concert with a fronto-insular network, is involved at the end of the target interval, and suggest a role in the duration categorization and decision making operations or alternatively in the preparedness of the timing of the future movement that will be executed during the reproduction phase. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Timing is essential to the execution of skilled movements, yet our knowledge of the neural systems underlying timekeeping operations is limited. Using whole-brain functional magnetic resonance imaging, subjects were imaged while tapping with their right index finger in synchrony with tones that were separated by constant intervals [Synchronization (S)], followed by tapping without the benefit of an auditory cue [Continuation (C)]. Two control conditions followed in which subjects listened to tones and then made pitch discriminations (D). Both the S and the C conditions produced equivalent activation within the left sensorimotor cortex, the right cerebellum (dorsal dentate nucleus), and the right superior temporal gyrus (STG). Only the C condition produced activation of a medial premotor system, including the caudal supplementary motor area (SMA), the left putamen, and the left ventrolateral thalamus. The C condition also activated a region within the right inferior frontal gyrus (IFG), which is functionally interconnected with auditory cortex. Both control conditions produced bilateral activation of the STG, and the D condition also activated the rostral SMA. These results suggest that the internal generation of precisely timed movements is dependent on three interrelated neural systems, one that is involved in explicit timing (putamen, ventrolateral thalamus, SMA), one that mediates auditory sensory memory (IFG, STG), and another that is involved in sensorimotor processing (dorsal dentate nucleus, sensorimotor cortex).

• 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]

To prepare timely motor actions, we constantly predict future events. Regularly repeating events are often perceived as a rhythm to which we can readily synchronize our movements, just as in dancing to music. However, the neuronal mechanisms underlying the capacity to encode and maintain rhythms are not understood. We trained nonhuman primates to maintain the rhythm of a visual metronome of diverse tempos and recorded neural activity in the supplementary motor area (SMA). SMA exhibited rhythmic bursts of gamma band (30–40 Hz) reflecting an internal tempo that matched the extinguished visual metronome. Moreover, gamma amplitude increased throughout the trial, providing an estimate of total elapsed time. Notably, the timing of gamma bursts and firing rate modulations allowed predicting whether monkeys were ahead or behind the correct tempo. Our results indicate that SMA uses dynamic motor plans to encode a metronome for rhythms and a stopwatch for total elapsed time.

We examined the influence of anodal transcranial direct current stimulation (tDCS) over the supplementary motor area (SMA) on anticipatory postural adjustments (APAs) and center of pressure (COP) sway in older adults. The study enrolled 12 healthy older adult volunteers. Subjects received anodal tDCS (2 mA) or sham stimulation over the SMA for 15 min and performed a self-paced rapid upward arm movement task on a force plate before, immediately after, and 15 min after the stimulation condition. APAs were measured as the temporal difference between activation onset in the deltoid anterior (AD) and biceps femoris (BF) muscles. The root mean square (RMS) area of COP sway, sway path length, medio-lateral mean velocity, and antero-posterior mean velocity of standing posture were also measured before and after the stimulation condition during the task. Anodal tDCS of the SMA extended APAs and decreased COP sway path length immediately after and 15 min after stimulation compared to baseline. These findings suggest that anodal tDCS over the SMA enhanced APAs function and improved postural sway during rapid upward arm movement in older adults.