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BACKGROUND: There is a tendency to pay little attention to cognitive dysfunction after a subcortical stroke, resulting in this condition being overlooked. Damage to the brainstem may affect cognition, probably originating from the fronto-cerebellar circuit, but details remain obscure. OBJECTIVE: To investigate the effect of damage to pons on frontal function via the fronto-cerebellar circuit. METHODS: We measured frontal dynamic responses in patients with acute pontine ischemia during phonemic verbal fluency task using near-infrared spectroscopy (NIRS). Furthermore, to determine whether the fronto-cerebellar circuit is affected by pontine ischemia, 99 mTc-ECD single photon emission computed tomography (SPECT) was performed. RESULTS: Twenty-five patients with pontine isolated infarction met the criteria. Especially, 80 percent of the pontine lesioned patients affected cognition. The patients exhibited hyper-frontal activity according to the neuropsychological tests. Follow-up NIRS showed increased frontal activity as being linked to improved cognition. This may indicate the involvement of frontal activity in cognitive recovery. The SPECT showed consistently hyper-frontal perfusion as well as hypo-cerebellar perfusion. CONCLUSIONS: This suggested that hyper-frontal activity might contribute to compensation for cognitive dysfunction after pontine ischemia and that recovery from the cognitive deficits is attributable to frontal activity. [ABSTRACT FROM AUTHOR]

Despite the fact that any successful achievement of willed actions necessarily entails the sense of body ownership (the feeling of owning the moving body parts), it is still unclear how this happens. To address this issue at both behavioral and neural levels, we capitalized on sensory attenuation (SA) phenomenon (a self-generated stimulus is perceived as less intense than an identical externally generated stimulus). We compared the intensity of somatosensory stimuli produced by one's own intended movements and by movements of an embodied fake hand. Then, we investigated if in these two conditions SA was equally affected by interfering with the activity of the supplementary motor area (SMA; known to be related to motor intention and SA) using single-pulse transcranial magnetic stimulation. We showed that ownership of the fake hand triggered attenuation of somatosensory stimuli generated by its movements that were comparable to the attenuation of self-generated stimuli. Furthermore, disrupting the SMA eliminated the SA effect regardless of whether it was triggered by actual participant's movements or by illusory ownership. Our findings suggest that SA triggered by body ownership relies, at least in part, on the activation of the same brain structures as SA triggered by motor-related signals. [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]

Background: Obsessive-compulsive disorder affects about 1-3% of the total population. The rTMS method is used as an additional strategy in the treatment of obsessive-compulsive disorder in combination with medications. Methods: The participants suffered from medically resistant OCD were randomized into active and placebo treatment groups. The aim was to measure the effect of applying 1 Hz rTMS on both sides of the supplementary motor field and assessing overall health with the SF-36 QOL questionnaire. Results: After the administration of 25 rTMS sessions in the active stimulation group, a significant improvement in overall health compared with the placebo group was reported. The improvement remained stable in the follow-up phase. Conclusion: Participants with active rTMS have received a significant improvement in overall health as measured by SF-36 QOL. Probably rTMS is a suitable therapeutic option for patients with resistant OCD. [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]

The dorsal  mesial frontal cortex contains the supplementary motor area (SMA) and the pre-supplementary motor area (pre-SMA), which play an important role in action and cognition. Evidence from cytoarchitectonic, stimulation, and functional studies suggests structural and functional divergence between the two subregions. However, a microstructural map of these areas obtained in a representative sample of brains in a stereotaxic reference space is still lacking. In the present study we show that the dorsal mesial frontal motor cortex comprises two microstructurally different brain regions: area SMA and area pre-SMA. Area-specific cytoarchitectonic patterns were studied in serial histological sections stained for cell bodies of ten human postmortem brains. Borders of the two cortical areas were identified using image analysis and statistical features. The 3D reconstructed areas were transferred to a common reference space, and probabilistic maps were calculated by superimposing the individual maps. A coordinate-based meta-analysis of functional imaging data was subsequently performed using the two probabilistic maps as microstructurally defined seed regions. It revealed that areas SMA and pre-SMA were strongly co-activated with areas in precentral, supramarginal and superior frontal gyri, Rolandic operculum, thalamus, putamen and cerebellum. Both areas were related to motor functions, but area pre-SMA was involved in more complex processes such as learning, cognitive processes and perception. The here described subsequent analyses led to converging evidence supporting the microstructural, and functional segregation of areas SMA and pre-SMA, and maps will be made available to the scientific community to further elucidate the microstructural substrates of motor and cognitive control. [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).

[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]

Although some patients have successful peripheral nerve regeneration, a poor recovery of hand function often occurs after peripheral nerve injury. It is believed that the capability of brain plasticity is crucial for the recovery of hand function. The supplementary motor area may play a key role in brain remodeling after peripheral nerve injury. In this study, we explored the activation mode of the supplementary motor area during a motor imagery task. We investigated the plasticity of the central nervous system after brachial plexus injury, using the motor imagery task. Results from functional magnetic resonance imaging showed that after brachial plexus injury, the motor imagery task for the affected limbs of the patients triggered no obvious activation of bilateral supplementary motor areas. This result indicates that it is difficult to excite the supplementary motor areas of brachial plexus injury patients during a motor imagery task, thereby impacting brain remodeling. Deactivation of the supplementary motor area is likely to be a serious problem for brachial plexus injury patients in terms of preparing, initiating and executing certain movements, which may be partly responsible for the unsatisfactory clinical recovery of hand function.

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.

Music performance relies on the ability to learn and execute actions and their associated sounds. The process of learning these auditory-motor contingencies depends on the proper encoding of the serial order of the actions and sounds. Among the different serial positions of a behavioral sequence, the first and last (boundary) elements are particularly relevant. Animal and patient studies have demonstrated a specific neural representation for boundary elements in prefrontal cortical regions and in the basal ganglia, highlighting the relevance of their proper encoding. The neural mechanisms underlying the encoding of sequence boundaries in the general human population remain, however, largely unknown. In this study, we examined how alterations of auditory feedback, introduced at different ordinal positions (boundary or within-sequence element), affect the neural and behavioral responses during sensorimotor sequence learning. Analysing the neuromagnetic signals from 20 participants while they performed short piano sequences under the occasional effect of altered feedback (AF), we found that at around 150–200 ms post-keystroke, the neural activities in the dorsolateral prefrontal cortex (DLPFC) and supplementary motor area (SMA) were dissociated for boundary and within-sequence elements. Furthermore, the behavioral data demonstrated that feedback alterations on boundaries led to greater performance costs, such as more errors in the subsequent keystrokes. These findings jointly support the idea that the proper encoding of boundaries is critical in acquiring sensorimotor sequences. They also provide evidence for the involvement of a distinct neural circuitry in humans including prefrontal and higher-order motor areas during the encoding of the different classes of serial order.

The Supplementary Motor Area (SMA)—located in the superior and medial aspects of the superior frontal gyrus—is a preferential site of certain brain tumors and arteriovenous malformations, which often provoke the so-called SMA syndrome. The bulk of the literature studying this syndrome has focused on two of its most apparent symptoms: contralateral motor and speech deficits. Surprisingly, little attention has been given to working memory (WM) even though neuroimaging studies have implicated the SMA in this cognitive process. Given its relevance for higher-order functions, our main goal was to examine whether WM is compromised in SMA lesions. We also asked whether WM deficits might be reducible to processing speed (PS) difficulties. Given the connectivity of the SMA with prefrontal regions related to executive control (EC), as a secondary goal we examined whether SMA lesions also hampered EC. To this end, we tested 12 patients with lesions involving the left (i.e., the dominant) SMA. We also tested 12 healthy controls matched with patients for socio-demographic variables. To ensure that the results of this study can be easily transferred and implemented in clinical practice, we used widely-known clinical neuropsychological tests: WM and PS were measured with their respective Wechsler Adult Intelligence Scale indexes, and EC was tested with phonemic and semantic verbal fluency tasks. Non-parametric statistical methods revealed that patients showed deficits in the executive component of WM: they were able to sustain information temporarily but not to mentally manipulate this information. Such WM deficits were not subject to patients' marginal PS impairment. Patients also showed reduced phonemic fluency, which disappeared after controlling for the influence of WM. This observation suggests that SMA damage does not seem to affect cognitive processes engaged by verbal fluency other than WM. In conclusion, WM impairment needs to be considered as part of the SMA syndrome. These findings represent the first evidence about the cognitive consequences (other than language) of damage to the SMA. Further research is needed to establish a more specific profile of WM impairment in SMA patients and determine the consequences of SMA damage for other cognitive functions.

ObjectivePrimary monosymptomatic nocturnal enuresis (PMNE) refers to bed-wetting in children who have no other lower urinary tract symptoms and are never dry for more than 6 months. Our previous studies demonstrated that children with PMNE exhibited brain functional abnormalities compared with healthy controls; however, researches on the abnormalities in gray matter were limited. This study aimed to investigate brain structural changes in gray matter of children with PMNE using magnetic resonance imaging (MRI).MethodsGray matter volumes (GMVs) and gyrification indices (GIs) were calculated using voxel-based and surface-based morphometry analyses of structural MRI data acquired from 26 children with PMNE and 28 healthy children. To identify between-group differences in gray matter, two-sample t-tests were conducted on GMV and GI images separately.ResultsCompared with the controls, children with PMNE showed significantly increased GMVs in the supplementary motor area and medial prefrontal cortex regions (mean GMV in PMNE: 0.54 ± 0.07 l; mean GMV in controls: 0.50 ± 0.06 l) and reduced GIs in the right precuneus (mean GI in PMNE: 25.74° ± 2.34°; mean GI in controls: 27.97° ± 1.79°).ConclusionChildren with PMNE showed abnormal GMVs in frontal lobe and GIs in precuneus, and these changes might be involved in the pathological mechanism of PMNE.