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The question how the brain distinguishes between information about oneself and the rest of the world is of fundamental interest to both philosophy and neuroscience. This question can be approached empirically by investigating how associating stimuli with oneself leads to differences in neurocognitive processing. However, little is known about the brain network involved in forming such self-associations for, specifically, bodily stimuli. In this fMRI study, we sought to distinguish the neural substrates of representing a full-body movement as one’s movement and as someone else’s movement. Participants performed a delayed match-to-sample working memory task where a retained full-body movement (displayed using point-light walkers) was arbitrarily labelled as one’s own movement or as performed by someone else. By using arbitrary associations we aimed to address a limitation of previous studies, namely that our own movements are more familiar to us than movements of other people. A searchlight multivariate decoding analysis was used to test where information about types of movement and about self-association was coded. Movement specific activation patterns was found in a network of regions also involved in perceptual processing of movement stimuli, however not in early sensory regions. Information about whether a memorized movement was associated with the self or with another person was found to be coded by activity in the left middle frontal gyrus (MFG), left inferior frontal gyrus (IFG), bilateral supplementary motor area, and (at reduced threshold) in the left temporoparietal junction (TPJ). These areas are frequently reported as involved in action understanding (IFG, MFG) and domain-general self/other distinction (TPJ). Finally, in univariate analysis we found that selecting a self-associated movement for retention was related to increased activity in the ventral medial prefrontal cortex.

Motor impairment in Parkinson's disease (PD) reflects changes in the basal ganglia-thalamocortical circuit converging on the primary motor cortex (M1) and supplementary motor area (SMA). Previous studies assessed M1 excitability in PD using transcranial magnetic stimulation (TMS)-evoked electromyographic activity. TMS-evoked electroencephalographic activity may unveil broader motor cortical network changes in PD.The aim was to assess motor cortical network excitability in PD.We compared TMS-evoked cortical potentials (TEPs) from M1 and the pre-SMA between 20 PD patients tested off and on medication and 19 healthy controls (HCs) and investigated possible correlations with bradykinesia.Off PD patients compared to HCs had smaller P30 responses from the M1s contralateral (M1+) and ipsilateral (M1-) to the most bradykinetic side and increased pre-SMA N40. Dopaminergic therapy normalized the amplitude of M1+ and M1- P30 as well as pre-SMA N40. We found a positive correlation between M1+ P30 amplitude and bradykinesia in off PD patients.Changes in M1 P30 and pre-SMA N40 in PD suggest that M1 excitability is reduced on both sides, whereas pre-SMA excitability is increased. The effect of dopaminergic therapy and the clinical correlation suggest that these cortical changes may reflect abnormal basal ganglia-thalamocortical activity. TMS electroencephalography provides novel insight into motor cortical network changes related to the pathophysiology of PD. © 2022 International Parkinson and Movement Disorder Society.

Sensorimotor abnormalities are common in autism spectrum disorder (ASD) and predictive of functional outcomes, though their neural underpinnings remain poorly understood. Using functional magnetic resonance imaging, we examined both brain activation and functional connectivity during visuomotor behavior in 27 individuals with ASD and 30 typically developing (TD) controls (ages 9–35 years). Participants maintained a constant grip force while receiving visual feedback at three different visual gain levels. Relative to controls, ASD participants showed increased force variability, especially at high gain, and reduced entropy. Brain activation was greater in individuals with ASD than controls in supplementary motor area, bilateral superior parietal lobules, and contralateral middle frontal gyrus at high gain. During motor action, functional connectivity was reduced between parietal‐premotor and parietal‐putamen in individuals with ASD compared to controls. Individuals with ASD also showed greater age‐associated increases in functional connectivity between cerebellum and visual, motor, and prefrontal cortical areas relative to controls. These results indicate that visuomotor deficits in ASD are associated with atypical activation and functional connectivity of posterior parietal, premotor, and striatal circuits involved in translating sensory feedback information into precision motor behaviors, and that functional connectivity of cerebellar–cortical sensorimotor and nonsensorimotor networks show delayed maturation., We used functional MRI to examine brain activation and functional connectivity during visuomotor behavior in individuals with ASD and typically developing controls. Results indicated that atypical sensorimotor behavior in ASD was linked to increased functional activation and decreased task‐dependent functional connectivity throughout the visuomotor network. Our results suggest that atypical modulation of sensory feedback information during precision refinement of ongoing motor behavior contributes to multiple developmental disruptions in affected individuals.

Previous studies showed reduced activity of the anterior cingulate cortex (ACC) and supplementary motor area during inhibition in children with attention-deficit/hyperactivity disorder (ADHD). This study aimed to investigate deep brain generators underlying alterations of evoked potential components triggered by visual GO/NoGO tasks in children with ADHD compared with typically developing children (TDC). Standardized weighted low-resolution electromagnetic tomography (swLORETA) source analysis showed that lower GO-P3 component in children with ADHD was explained not only by a reduced contribution of the frontal areas but also by a stronger contribution of the anterior part of the caudate nucleus in these children compared with TDC. While the reduction of the NoGO-P3 component in children with ADHD was essentially explained by a reduced contribution of the dorsal ACC, the higher NoGO-P2 amplitude in these children was concomitant to the reduced contribution of the dorsolateral prefrontal cortex, the insula, and the cerebellum. These data corroborate previous findings showed by fMRI studies and offered insight relative to the precise time-related contribution of the caudate nucleus and the cerebellum during the automatic feature of inhibition processes in children with ADHD. These results were discussed regarding the involvement of the fronto-basal ganglia and fronto-cerebellum networks in inhibition and attention alterations in ADHD., SCOPUS: ar.j, info:eu-repo/semantics/published

Prior neuroimaging studies have supported the idea that the human insular cortex plays an important role in processing and representing internal bodily states, also termed "interoception." According to recent theoretical studies, interoception includes several aspects such as attention and accuracy. However, there is no consensus on the laterality and location of the insula to support each aspect of interoception. Thus, we aimed to identify the anatomical insular subdivisions involved in interoceptive attention and accuracy; we examined 28 healthy volunteers who completed the behavioral heartbeat counting task and interoceptive attention paradigm using functional magnetic resonance imaging. First, interoceptive attention induced significant activation in the bilateral frontal operculum, precentral gyrus, middle insula, middle cingulate cortex, and supplementary motor area. Then, we compared the activation in anatomically predefined insular subdivisions during interoceptive attention. The highest activation of the middle short gyrus was noted within the insular cortex, followed by the anterior short gyrus and posterior short gyrus, while no significant hemispheric differences were observed. Finally, the interoceptive accuracy index, measured using the heartbeat counting task, strongly correlated with the activity of the right dorsal anterior insula/frontal operculum. These findings suggest that interoceptive attention is associated with the bilateral dorsal mid-anterior insula, which supports the processing and representation of bodily signals. In contrast, the more dorsal anterior portion of the right insula plays a key role in obtaining accurate interoception.

AIM To explore the feasibility and possible effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the supplementary motor area (SMA) on tic severity and motor system neurophysiology in children with Tourette syndrome. METHOD Ten children with Tourette syndrome (eight males, two females; 9-15y) participated in this open-label, phase 1 clinical trial. Treatment consisted of 1800 low-frequency (1Hz) neuronavigated robotic rTMS (100% resting motor threshold) to the SMA, bilaterally for 15 sessions. The primary outcome was a change in Yale Global Tic Severity Scale (YGTSS) total score from baseline to posttreatment. Secondary outcome measures included changes in magnetic resonance spectroscopy metabolite concentrations, TMS neurophysiology measures, TMS motor maps, and clinical assessments (anxiety, depression) from baseline to the end of treatment. RESULTS The YGTSS score decreased from baseline after treatment (p

Introduction The brain's role in bladder control has become an important area of study in the last 15 years. Typically, the brain's role in urinary urgency has been studied by repeated infusion and withdrawal of fluid, per catheter, to provoke urgency sensation during a whole brain magnetic resonance imaging (MRI) scan. Since this technique generally requires a large group size, we tested a more intense infusion-withdrawal protocol in an attempt to improve signal to noise ratio and repeatability of the signal which would, in turn, allow us to further probe subtypes of urgency urinary incontinence. Methods A total of 12 women over the age of 60 were recruited to test a new "intense" infusion withdrawal protocol. They underwent this new protocol during a functional brain MRI scan. The primary outcome was comparison of activity within the insula, medial pre-frontal cortex and dorsal anterior cingulate cortex/supplementary motor area (dACC/SMA). Immediate test-retest repeatability was measured using intraclass correlation. Secondary exploratory evaluation of differences in the whole brain between protocols was conducted. Results There was no significant difference in signal in any of the a priori regions of interest between protocols. Test-retest repeatability in the new protocol was poor compared to the original protocol, and variability was higher. Three participants were not able to tolerate the "intense" protocol. Conclusion The small improvement in signal to noise ratio of the new protocol was not sufficient to overcome the poorly tolerated intense filling protocol.

Behavioral findings suggest that aging alters the involvement of cortical sensorimotor mechanisms in postural control. However, corresponding accounts of the underlying neural mechanisms remain sparse, especially the extent to which these mechanisms are affected during more demanding tasks. Here, we set out to elucidate cortical correlates of altered postural stability in younger and older adults. 3D body motion tracking and high-density electroencephalography (EEG) were measured while 14 young adults (mean age = 24 years, 43% women) and 14 older adults (mean age = 77 years, 50% women) performed a continuous balance task under four different conditions. Manipulations were applied to the base of support (either regular or tandem (heel-to-toe) stance) and visual input (either static visual field or dynamic optic flow). Standing in tandem, the more challenging position, resulted in increased sway for both age groups, but for the older adults, only this effect was exacerbated when combined with optic flow compared to the static visual display. These changes in stability were accompanied by neuro-oscillatory modulations localized to midfrontal and parietal regions. A cluster of electro-cortical sources localized to the supplementary motor area showed a large increase in theta spectral power (4-7 Hz) during tandem stance, and this modulation was much more pronounced for the younger group. Additionally, the older group displayed widespread mu (8-12 Hz) and beta (13-30 Hz) suppression as balance tasks placed more demands on postural control, especially during tandem stance. These findings may have substantial utility in identifying early cortical correlates of balance impairments in otherwise healthy older adults.

Aim Sports activities provide social interaction for humans. Commitment to a given team is a salient feature of being a sports fan and becomes a prominent part of self-identification for fanatics. Emotion, subjective hedonic experience, and non-romantic love are related to fan behaviors. Few studies have evaluated the neural basis of sports fanaticism. Methods Thirty men, including 16 football fanatics and 14 non-fanatics, with a mean age of 27.4 ± 6.4 years (range, 20-48 years) were enrolled. Subjects underwent functional MRI while watching a set of goals scored by favorite, rival, and neutral teams. Results The analysis of variance in a general linear model revealed a significant Group × Condition interaction effect in the bilateral dorsal anterior cingulate cortex (dACC) that was more prominent in the left hemisphere. In the post-hoc comparisons, fanatics showed increased activation in bilateral dACC, supplementary motor area, superior frontal cortex, right dorsolateral prefrontal cortex, and right insula for Favorite > Neutral contrast and an increased activation in bilateral dACC and supplementary motor area for Rival > Neutral contrast. Seed-based connectivity analyses using the areas with significant activation differences revealed increased connectivity between dACC and several regions, including the left posterior lateral temporal area, insula, bilateral medial temporal area, and medial superior frontal area as well as the basal ganglia in fanatics compared to non-fanatics. Conclusion Our results suggest that football fanatics exhibit a different brain activation and connectivity pattern from non-fanatics, both under favorable and unfavorable conditions. This brain activity and connectivity pattern under emotionally laden conditions may represent higher responses to rewards, higher emotional valence attribution, and stronger motivational state of football fanatics, which might underlie their unusual behavioral responses.

OBJECTIVE Bipolar disorder (BD) has been associated with abnormal reward functioning including pleasure-seeking and impulsivity. Here we sought to clarify whether these changes can be attributed to abnormalities in the neural processing of reward valuation or error prediction. Moreover, we tested whether abnormalities in these processes are associated with familial vulnerability to BD. METHODS We obtained functional magnetic resonance imaging data from patients with recently diagnosed BD (n = 85), their unaffected first-degree relatives (n = 44), and healthy control participants (n = 66) while they were performing a monetary card game. We used a region-of-interest approach to test for group differences in the activation of the midbrain, the ventral striatum, and the prefrontal cortex during reward valuation and error prediction. RESULTS Patients with BD showed decreased prediction error signal in ventrolateral prefrontal cortex and the unaffected relatives showed decreased prediction error signal in the supplementary motor area in comparison to healthy controls. There were no significant group differences in the activation of the ventral striatum during the task. In healthy controls, prediction error signal in dorsal anterior cingulate cortex correlated with an out-of-scanner measure of motor inhibition but this association was absent in patients and relatives. CONCLUSIONS The findings indicate that abnormal reward processing in BD is primarily related to deficits in the engagement of prefrontal regions involved in inhibitory control during error prediction. In contrast, deficient activation in supplementary motor cortex involved in planning of movement emerged as a familial vulnerability to BD.

It is widely accepted that unexpected sensory consequences of self‐action engage the cerebellum. However, we currently lack consensus on where in the cerebellum, we find fine‐grained differentiation to unexpected sensory feedback. This may result from methodological diversity in task‐based human neuroimaging studies that experimentally alter the quality of self‐generated sensory feedback. We gathered existing studies that manipulated sensory feedback using a variety of methodological approaches and performed activation likelihood estimation (ALE) meta‐analyses. Only half of these studies reported cerebellar activation with considerable variation in spatial location. Consequently, ALE analyses did not reveal significantly increased likelihood of activation in the cerebellum despite the broad scientific consensus of the cerebellum's involvement. In light of the high degree of methodological variability in published studies, we tested for statistical dependence between methodological factors that varied across the published studies. Experiments that elicited an adaptive response to continuously altered sensory feedback more frequently reported activation in the cerebellum than those experiments that did not induce adaptation. These findings may explain the surprisingly low rate of significant cerebellar activation across brain imaging studies investigating unexpected sensory feedback. Furthermore, limitations of functional magnetic resonance imaging to probe the cerebellum could play a role as climbing fiber activity associated with feedback error processing may not be captured by it. We provide methodological recommendations that may guide future studies.

Objective To report clinical experience with presurgical evaluation in patients with insulo‐opercular epilepsy. Quantitative analysis on PET imaging and stereoelectroencephalography (SEEG) signals was used to summarize their electroclinical features. Methods Twenty‐two patients with focal epilepsy arising from the insular and/or opercular cortex according to SEEG were retrospectively analyzed. Presurgical noninvasive data were analyzed in detail. Interictal PET data of patients were then statistically compared with those of healthy controls to identify the interictal hypometabolic network. The epileptogenicity index (EI) of ictal SEEG signal was computed to identify areas of spread at the beginning of seizure onset. Results Focal tonic seizures of the face and/or neck (16/22, 73%) were the most prevalent early objective signs. Epileptic discharges in the interictal and ictal scalp‐EEG mostly showed an ipsilateral perisylvian distribution. Statistical analysis of interictal PET showed significant hypometabolism in the insular lobe, central operculum, supplementary motor area, middle cingulate cortex, bilateral caudate nuclei, and putamen. According to the EI analysis, insulo‐opercular epilepsy could be classified as insulo‐opercular epilepsy (50%), opercular epilepsy (41%), and insular cortex epilepsy (9%). Significance Clinical diagnosis of insulo‐opercular epilepsy is challenging because of its complex seizure semiology and nonlocalizing discharges on scalp‐EEG. A common hypometabolic network involving the insulo‐opercular cortex, mesial frontal cortex and subcortical nuclei may be involved in the organization of the insulo‐opercular epilepsy network. Furthermore, quantified SEEG analysis suggested that pure insular epilepsy is rare, and the close connection between insular and opercular cortex necessitates SEEG implantation to define the epileptogenic zone.

AIMS: In the human brain, supplementary motor area (SMA) is involved in the control of pelvic floor muscles. SMA dysfunction has been implicated in several disorders involving pelvic floor muscles, including urinary incontinence and urologic pain. Here we aimed to provide a proof-of-concept study to demonstrate the feasibility of modulating resting pelvic floor muscle activity (tone) as well as SMA activity with non-invasive 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. Pelvic floor muscle 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 pelvic floor muscles (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.

Mirror neurons (MN) have been proposed as the neural substrate for a wide range of clinical, social and cognitive phenomena. Over the last decade, a commonly used tool for investigating MN activity in the human brain has been functional magnetic resonance (f MRI ) repetition suppression (RS ) paradigms. However, the available evidence is mixed, largely owing to inconsistent application of the methodological criteria necessary to infer MN properties. This raises concerns about the degree to which one can infer the presence (or absence) of MN activity from earlier accounts that adopted RS paradigms. We aimed to clarify this issue using a well‐validated f MRI RS paradigm and tested for mirror properties by rigorously applying the widely accepted criteria necessary to demonstrate MN activity using traditional univariate techniques and Multivariate Pattern Analysis (MVPA ). While univariate whole brain analysis in healthy adults showed uni‐modal RS effects within the supplementary motor area, no evidence for cross‐modal RS effects consistent with mirror neuron activity was found. MVPA on the other hand revealed a region along the anterior intraparietal sulcus that met the criteria for MN activity. Taken together, these results clarify disparate evidence from earlier RS studies, highlighting that traditional univariate analysis of RS data may not be sensitive for detecting MN activity when rigorously applying the requisite criteria. In light of these findings, we recommend that short of increasing sample sizes substantially, future studies using RS paradigms to investigate MN s across the human brain consider the use of MVPA.

Abundant behavioral studies have demonstrated high comorbidity of reading and handwriting difficulties in developmental dyslexia (DD), a neurological condition characterized by unexpectedly low reading ability despite adequate nonverbal intelligence and typical schooling. The neural correlates of handwriting deficits remain largely unknown; however, as well as the extent that handwriting deficits share common neural bases with reading deficits in DD. The present work used functional magnetic resonance imaging to examine brain activity during handwriting and reading tasks in Chinese dyslexic children (n = 18) and age-matched controls (n = 23). Compared to controls, dyslexic children exhibited reduced activation during handwriting tasks in brain regions supporting sensory-motor processing (including supplementary motor area and postcentral gyrus) and visual-orthography processing (including bilateral precuneus and right cuneus). Among these regions, the left supplementary motor area and the right precuneus also showed a trend of reduced activation during reading tasks in dyslexics. Moreover, increased activation was found in the left inferior frontal gyrus and anterior cingulate cortex in dyslexics, which may reflect more efforts of executive control to compensate for the impairments of motor and visual-orthographic processing. Finally, dyslexic children exhibited aberrant functional connectivity among brain areas for cognitive control and sensory-motor processes during handwriting tasks. Together, these findings suggest that handwriting deficits in DD are associated with functional abnormalities of multiple brain regions implicated in motor execution, visual-orthographic processing, and cognitive control, providing important implications for the diagnosis and treatment of dyslexia.

Background Crohn's disease (CD) is a chronic recurrent intestinal inflammatory disease, often accompanied by poor adaptation and excessive stress response. However, the potential neurological mechanisms of these symptoms have not yet been studied in‐depth. Objective To investigate alterations in brain activity in patients with Crohn's disease and study the relationship between altered regions and clinical indices. Methods A total of 15 CD patients and 26 matched healthy controls were recruited. All participants underwent fMRI scans. The amplitude of low‐frequency fluctuations (ALFF) and regional homogeneity (ReHo) assessed differences in spontaneous regional brain activity. Differences between the groups were selected as seeds for functional connectivity (FC) analyses. Correlations between disease duration and ALFF/ReHo/FC values in abnormal regions were analyzed. Results Patients with CD had significantly higher ALFF values in the left superior frontal gyrus, anterior cingulate cortex, and supplementary motor area, and lower values in the left hippocampus. They also had higher ReHo values in the left anterior cingulate cortex, supplementary motor area, putamen, and the bilateral superior frontal gyri. FC strength in the left precentral and middle temporal gyri was found to be increased when the left superior frontal gyrus was used as the seed point. FC strength was also observed to be increased in the left postcentral, middle frontal gyri, inferior frontal orbital cortex, and right rolandic operculum when the left anterior cingulate cortex was used as the seed point. Conclusion CD demonstrated abnormal neural activity and FC in various regions primarily associated with emotional, pain and cognitive‐related functions, which provides more information to further understand the neural mechanisms of the disease., This study investigated the altered brain activity and connectivity in CD patients by using rs‐fMRI with ALFF, ReHo, FC analysis. CD demonstrated abnormal neural activity and functional connectivity in various regions mainly related to emotion and mood function, which provide more information to further understand of neural mechanisms of the disease.

Background Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID) with a high prevalence in clinical practice. Previous studies have identified that FCon is associated with functional and structural alterations in the primary brain regions involved in emotional arousal processing, sensory processing, somatic/motor-control, and self-referential processing. However, whether FCon is associated with abnormal structural connectivity (SC) among these brain regions remains unclear. Methods We selected the brain regions with functional and structural abnormalities as seed regions and employed diffusion tensor imaging (DTI) with probabilistic tractography to investigate SC changes in 29 patients with FCon and 31 healthy controls (HC). Key results Results showed lower fractional anisotropy (FA) in the fibers connecting the thalamus, a region involved in sensory processing, with the amygdala (AMY), hippocampal gyrus (HIPP), precentral (PreCen) and postcentral gyrus (PostCen), supplementary motor area (SMA) and precuneus in patients with FCon compared with HC. FCon had higher mean diffusivity (MD) and radial diffusivity (RD) in the thalamus connected to the AMY and HIPP. In addition, FCon had significantly increased RD of the thalamus-SMA tract. Sensation of incomplete evacuation was negatively correlated with FA of the thalamus-PostCen and thalamus-HIPP tracts, and there was a negative correlation between difficulty of defecation and FA of the thalamus-SMA tract. Conclusions and inferences These findings reflected that FCon is associated with alterations in SC between the thalamus and limbic/parietal cortex, highlighting the integrative role of the thalamus in brain structural network.

We studied gray matter volume covariance networks associated with normal pace walking (NPW) speed and dual-task costs (DTCs) during walking-while-talking (WWT)-a mobility stress test that involves walking while reciting alternate letters of the alphabet. Using a multivariate covariance-based analytic approach, we identified gray matter networks associated with NPW speed (mean 102.1 cm/s ±22.5 cm/s) and DTC (percent difference in gait speed between NPW and WWT, mean 25.9% ± 18.8%) in 139 older adults without dementia (M = 75.3 ± 6.1 years). The gray matter network associated with NPW was primarily composed of supplementary motor area, precuneus cortex, and the middle frontal gyrus. Greater expression of this NPW network was associated with better processing speed (trail-making test A [r = -0.30, p = 0.005]) and executive function (trail-making test B - A [r = -0.43, p < 0.0001]). The gray matter network associated with DTC was primarily composed of medial prefrontal, cingulate, and thalamic regions. Greater expression of this DTC network was associated with better episodic memory performance on the free and cued selective reminding test (r = 0.30, p = 0.007). These results suggest that NPW speed and DTC are supported by different networks, and are associated with different cognitive domains.

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.

An intention to move distorts the perception of time. For example, a visual stimulus presented during the preparation of manual movements is perceived longer than actual. Although neural mechanisms underlying this action‐induced time distortion have been unclear, here we propose a new model in which the distortion is caused by a sensory–motor interaction mediated by alpha rhythm. It is generally known that viewing a stimulus induces a reduction in amplitude of occipital 10‐Hz wave (“alpha‐blocking”). Preparing manual movements are also known to reduce alpha power in the motor cortex (“mu‐suppression”). When human participants prepared movements while viewing a stimulus, we found that those two types of classical alpha suppression interacted in the third (time‐processing) region in the brain, inducing a prominent decrease in alpha power in the supplementary motor cortex (SMA). Interestingly, this alpha suppression in the SMA occurred in an asymmetric manner (such that troughs of alpha rhythm was more strongly suppressed than peaks), which can produce a gradual increase (slow shift of baseline) in neural activity. Since the neural processing in the SMA encodes a subjective time length for a sensory event, the increased activity in this region (by the asymmetric alpha suppression) would cause an overestimation of elapsed time, resulting in the action‐induced time distortion. Those results showed a unique role of alpha wave enabling communications across distant (visual, motor, and time‐processing) regions in the brain and further suggested a new type of sensory–motor interaction based on neural desynchronization (rather than synchronization).

Reach movements are characterized by multiple kinematic variables that can change with age or due to medical conditions such as movement disorders. While the neural control of reach direction is well investigated, the elements of the neural network regulating speed (the nondirectional component of velocity) remain uncertain. Here, we used a custom made magnetic resonance (MR)-compatible arm movement tracking system to capture the real kinematics of the arm movements while measuring brain activation with functional magnetic resonance imaging to reveal areas in the human brain in which BOLD-activation covaries with the speed of arm movements. We found significant activation in multiple cortical and subcortical brain regions positively correlated with endpoint (wrist) speed (speed-related activation), including contralateral premotor cortex (PMC), supplementary motor area (SMA), thalamus (putative VL/VA nuclei), and bilateral putamen. The hand and arm regions of primary sensorimotor cortex (SMC) and a posterior region of thalamus were significantly activated by reach movements but showed a more binary response characteristics (movement present or absent) than with continuously varying speed. Moreover, a subregion of contralateral SMA also showed binary movement activation but no speed-related BOLD-activation. Effect size analysis revealed bilateral putamen as the most speed-specific region among the speed-related clusters whereas primary SMC showed the strongest specificity for movement versus non-movement discrimination, independent of speed variations. The results reveal a network of multiple cortical and subcortical brain regions that are involved in speed regulation among which putamen, anterior thalamus, and PMC show highest specificity to speed, suggesting a basal-ganglia-thalamo-cortical loop for speed regulation.

Right-IFG and pre-SMA are associated with inhibitory responses. We used functional Magnetic Resonance Imaging to explore whether the contralateral homotopic regions can functionally replace them. An adolescent, with an extensive traumatic lesion of the right cerebral hemisphere having occurred 5 years earlier, performed a motor response inhibition task (Go/Nogo), which was properly accomplished and associated to activations in the left-IFC, precuneus and occipital cortex. Such functional remodelling is in line with the theory of 'near equipotentiality' of the cerebral hemispheres.

Summary Objective Genetic generalized epilepsies (GGEs) are characterized by generalized spike‐wave discharges (GSWDs) in electroencephalography (EEG) recordings without underlying structural brain lesions. The origin of the epileptic activity remains unclear, although several studies have reported involvement of thalamus and default mode network (DMN). The aim of the current study was to investigate the networks involved in the generation and temporal evolution of GSWDs to elucidate the origin and propagation of the underlying generalized epileptic activity. Methods We examined 12 patients with GGE and GSWDs using EEG–functional magnetic resonance imaging (fMRI) and identified involved brain areas on the basis of a classical general linear model (GLM) analysis. The activation time courses of these areas were further investigated to reveal their temporal sequence of activations and deactivations. Dynamic causal modeling (DCM) was used to determine the generator of GSWDs in GGE. Results We observed activity changes in the thalamus, DMN, dorsal attention network (DAN), salience network (SN), basal ganglia, dorsolateral prefrontal cortex, and motor cortex with supplementary motor area, however, with a certain heterogeneity between patients. Investigation of the temporal sequence of activity changes showed deactivations in the DMN and DAN and activations in the SN and thalamus preceding the onset of GSWDs on EEG by several seconds. DCM analysis indicated that the DMN gates GSWDs in GGE. Significance The observed interplay between DMN, DAN, SN, and thalamus may indicate a downregulation of consciousness. The DMN seems to play a leading role as a driving force behind these changes. Overall, however, there were also clear differences in activation patterns between patients, reflecting a certain heterogeneity in this cohort of GGE patients.

Functional magnetic resonance imaging (fMRI) is widely used for investigating brain activation patterns associated with chewing and clenching movements. Whether studies consistently identify similar brain loci engaged in these movements remains unknown. We investigated the consistency with which specific brain loci were reported to be activated during teeth-occluding movements, using the activation likelihood estimation (ALE) meta-analysis. Twenty fMRI studies that used fMRI to investigate brain activation during a chewing or clenching task in healthy participants were included. Data from the selected studies were pooled, and ALE methods were used to estimate the likelihood of finding a locus associated with the movements. We found that (i) The bilateral primary motor cortex/supplementary motor area/thalamus, the right primary somatosensory cortex (S1)/secondary somatosensory cortex and the posterior cerebellum (lobule VI) have been identified as reliable loci that show consistently activation when teeth occlude. (ii) The right S1 showed a significant likelihood of activation associated with both chewing and clenching, while the left S1 showed a greater likelihood of activation in chewing than in clenching. (iii) Both younger and older participants showed a significant likelihood of activation in the cerebellum. No significant cluster was identified in the contrast analysis. The fMRI studies reliably identified the sensorimotor cortex, the thalamus and the cerebellum as brain loci associated with chewing and clenching and illustrated a differential activation pattern between chewing and clenching. These findings support the use of fMRI as a potential tool for assessing brain activation patterns related to oral sensorimotor functions in humans.

Glutamate has been implicated in exercise-induced fatigue, but the underlying mechanism is unknown. This study aimed to determine whether glutamate transporter-1 (GLT-1) has a key role in the regulation of exercise-induced fatigue. The expressions of GLT-1 and glial fibrillary acidic protein (GFAP) in the supplementary motor area of rats exposed to exhaustion were analyzed by immunohistochemistry. The expression of GLT-1 was further confirmed by Western blotting. The effects of GLT-1 on extracellular levels of glutamate and lactate and on exercise endurance were studied by microdialysis. GLT-1 expression was decreased in rats subjected to exercise-induced fatigue. Functional inhibition of GLT-1 using dihydrokainate and transcriptional inhibition of GLT-1 using antisense oligodeoxynucleotides led to a decrease in exercise endurance with a subsequent increase in extracellular glutamate concentration and decrease in extracellular lactate concentration. The expression of GLT-1 in the supplementary motor area is reduced after strenuous exercise, resulting in an increased extracellular glutamate concentration and decreased extracellular lactate level that may be responsible for the development of fatigue. GLT-1-mediated uptake of glutamate ameliorates exercise-induced fatigue in rat models.

To date, fractionation of the nicotine addiction phenotype has been limited to that based primarily on characteristics of cigarette use, although it is widely appreciated that a variety of individual factors are associated with tobacco use disorder. Identifying subtypes of tobacco use disorder based on such factors may lead to better understanding of potential treatment targets, individualize treatments and improve outcomes. In this preliminary study, to identify potential subgroups, we applied hierarchical clustering to a broad range of assessments measuring personality, IQ and psychiatric symptoms, as well as various environmental and experiential characteristics from 102 otherwise healthy cigarette smokers. The identified subgroups were further compared on various resting-state fMRI measures from a subset (N = 65) of individuals who also underwent resting-state fMRI scanning. The clustering dendrogram indicated that smokers can be divided into three subgroups. Each subgroup had unique clinical assessment characteristics. The division yielded imaging differences between subgroups in the supplementary motor area/middle cingulate cortex and the cuneus. Regression analyses showed that amplitude of low frequency fluctuations in the supplementary motor area/middle cingulate cortex differed between groups and were negatively correlated with the Toronto Alexithymia Scale subscale Difficulty Describing Feelings.

Complex motor sequencing and sensory integration are two key items in scales assessing neurological soft signs. However, the underlying neural mechanism and heritability of these two functions is not known. Using a healthy twin design, we adopted two functional brain imaging tasks focusing on fist‐edge‐palm (FEP) complex motor sequence and audiovisual integration (AVI). Fifty‐six monozygotic twins and 56 dizygotic twins were recruited in this study. The pre‐ and postcentral, temporal and parietal gyri, the supplementary motor area, and the cerebellum were activated during the FEP motor sequence, whereas the precentral, temporal, and fusiform gyri, the thalamus, and the caudate were activated during AVI. Activation in the supplementary motor area during FEP motor sequence and activation in the precentral gyrus and the thalamic nuclei during AVI exhibited significant heritability estimates, ranging from 0.5 to 0.62. These results suggest that activation in cortical motor areas, the thalamus and the cerebellum associated with complex motor sequencing and audiovisual integration function may be heritable.

To understand how the information derived from different motor cortical areas representing different body parts is organized in the basal ganglia, we examined the neuronal responses in the subthalamic nucleus (STN), and the external (GPe) and internal (GPi) segments of the globus pallidus (input, relay and output nuclei, respectively) to stimulation of the orofacial, forelimb and hindlimb regions of the primary motor cortex (MI) and supplementary motor area (SMA) in macaque monkeys under the awake state. Most STN and GPe/GPi neurons responded exclusively to stimulation of either the MI or SMA, and one‐fourth to one‐third of neurons responded to both. STN neurons responding to the hindlimb, forelimb and orofacial regions of the MI were located along the medial–lateral axis in the posterolateral STN, while neurons responding to the orofacial region of the SMA were located more medially than the others in the anteromedial STN. GPe/GPi neurons responding to the hindlimb, forelimb and orofacial regions of the MI were found along the dorsal–ventral axis in the posterolateral GPe/GPi, and neurons responding to the corresponding regions of the SMA were similarly but less clearly distributed in more anteromedial regions. Moreover, neurons responding to the distal and proximal forelimb MI regions were found along the lateral–medial axis in the STN and the ventral–dorsal axis in the GPe/GPi. Most STN and GPe/GPi neurons showed kinaesthetic responses with similar somatotopic maps. These observations suggest that the somatotopically organized inputs from the MI and SMA are well preserved in the STN and GPe/GPi with partial convergence.

Developmental Coordination Disorder (DCD) is as a neurodevelopmental condition characterized by poor motor proficiency, which impacts academic performance and activities of daily living. Several studies have determined that children with DCD activate different regions of the brain when performing motor skills in comparison to typically developing (TD) children. However, none have used Functional Near-Infrared Spectroscopy (fNIRS) to explore cortical activation in this population. With that, the goal of this preliminary study was to investigate cortical activation using fNIRS in six children with DCD and six TD children between ages of 8 and 12 years. Three fine-motor tasks were performed: Finger Tapping (FT), Curve Tracing (CT), and Paragraph Writing (PW). Tasks were presented in counterbalanced order and had a baseline of 30s. Cortical activity elicited during performance of the FT, CT, and PW tasks was measured by fNIRS, and activation areas within each group were statistically compared. Results indicated that participant groups used different focal activation areas as well as different neural networks to perform the tasks. These distinct patterns were also task-specific, with differences in the right Pre-Motor Cortex (Pre-MC) and Supplementary Motor Area (SMA) for CT, and the right Dorsolateral Prefrontal Cortex (DLPFC) and the right Pre-MC for the PW task. These results add to the body of research exploring neurological alterations in children with DCD, and establish the feasibility of using fNIRS technology with this population.

Cognitive flexibility is essential to cope with changing task demands and often it is necessary to adapt to combined changes in a coordinated manner. The present fMRI study examined how the brain implements such multi‐level adaptation processes. Specifically, on a “local,” hierarchically lower level, switching between two tasks was required across trials while the rules of each task remained unchanged for blocks of trials. On a “global” level regarding blocks of twelve trials, the task rules could reverse or remain the same. The current task was cued at the start of each trial while the current task rules were instructed before the start of a new block. We found that partly overlapping and partly segregated neural networks play different roles when coping with the combination of global rule reversal and local task switching. The fronto‐parietal control network (FPN) supported the encoding of reversed rules at the time of explicit rule instruction. The same regions subsequently supported local task switching processes during actual implementation trials, irrespective of rule reversal condition. By contrast, a cortico‐striatal network (CSN) including supplementary motor area and putamen was increasingly engaged across implementation trials and more so for rule reversal than for nonreversal blocks, irrespective of task switching condition. Together, these findings suggest that the brain accomplishes the coordinated adaptation to multi‐level demand changes by distributing processing resources either across time (FPN for reversed rule encoding and later for task switching) or across regions (CSN for reversed rule implementation and FPN for concurrent task switching).

Advances in neuroimaging have enabled the mapping of white matter connections across the entire brain, allowing for a more thorough examination of the extent of white matter disconnection after stroke. To assess how cortical disconnection contributes to motor impairments, we examined the relationship between structural brain connectivity and upper and lower extremity motor function in individuals with chronic stroke. Forty-three participants [mean age: 59.7 (±11.2) years; time poststroke: 64.4 (±58.8) months] underwent clinical motor assessments and MRI scanning. Nonparametric correlation analyses were performed to examine the relationship between structural connectivity amid a subsection of the motor network and upper/lower extremity motor function. Standard multiple linear regression analyses were performed to examine the relationship between cortical necrosis and disconnection of three main cortical areas of motor control [primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA)] and motor function. Anatomical connectivity between ipsilesional M1/SMA and the (1) cerebral peduncle, (2) thalamus, and (3) red nucleus were significantly correlated with upper and lower extremity motor performance (P ≤ 0.003). M1-M1 interhemispheric connectivity was also significantly correlated with gross manual dexterity of the affected upper extremity (P = 0.001). Regression models with M1 lesion load and M1 disconnection (adjusted for time poststroke) explained a significant amount of variance in upper extremity motor performance (R2 = 0.36-0.46) and gait speed (R2 = 0.46), with M1 disconnection an independent predictor of motor performance. Cortical disconnection, especially of ipsilesional M1, could significantly contribute to variability seen in locomotor and upper extremity motor function and recovery in chronic stroke. Hum Brain Mapp 39:120-132, 2018. © 2017 Wiley Periodicals, Inc.

Reduced executive control is one of the central components of model on the development and maintenance of Internet gaming disorder (IGD). Among the various executive control problems, high impulsivity has consistently been associated with IGD. We performed voxel-based morphometric analysis with diffeomorphic anatomical registration by using an exponentiated Lie algebra algorithm (DARTEL) to investigate the relationship of gray matter abnormalities to impulsivity in IGD. Thirty-one young male adults whose excessive Internet gaming began in early adolescence, and 30 age-matched male healthy controls were examined. IGD subjects showed smaller gray matter volume (GMV) in brain regions implicated in executive control, such as the anterior cingulate cortex and the supplementary motor area. The GMVs in the anterior cingulate cortex and the supplementary motor area were negatively correlated with self-reporting scales of impulsiveness. IGD subjects also exhibited smaller GMV in lateral prefrontal and parietal cortices comprising the left ventrolateral prefrontal cortex and the left inferior parietal lobule when compared with healthy controls. The GMVs in the left ventrolateral prefrontal cortex were negatively correlated with lifetime usage of Internet gaming. These findings suggest that gray matter abnormalities in areas related to executive control may contribute to high impulsivity of young adults with IGD. Furthermore, alterations in the prefrontal cortex were related with long-term excessive Internet gaming during adolescence.

We tested the hypothesis that Gilles de la Tourette syndrome (GTS) is characterized by perturbed connectivity within cortico-subcortical motor networks. To this end, we performed a dynamic causal modelling (DCM) analysis of fMRI data collected during a finger opposition task in 24 normal controls and 24 GTS patients. The DCM analysis allowed us to assess whether any GTS-specific patterns of brain activity were related to intrinsic and/or to task-dependent connectivity. While no abnormalities were found for task-dependent connectivity, intrinsic connectivity was abnormally increased in the premotor network, with stronger connections from the supplementary motor area (SMA), from the dorsolateral premotor cortex and from the putamen to the right superior frontal gyrus, an area where GTS showed over-activation in a previous univariate analysis. We also found a positive correlation between the connectivity strength from the right basal ganglia to the right primary motor cortex (M1) and disease severity measured by the Yale Global Tic Severity Scale (YGTSS). This pattern was mirrored by a negative correlation between the connection strength from the right SMA to the right area M1 and the YGTSS score. These two reverse correlation effects showed a specific relationship with individual disease severity: the greater the imbalance between subcortical and premotor connectivity towards area M1, the higher the YGTSS score. These results reveal the existence of perturbed intrinsic connectivity patterns in the motor networks of GTS patients with two competing forces operating in a tug of war-like mechanism: aberrant subcortical afferents to M1, compensated for by inputs from the premotor cortex.

Response inhibition mechanisms are mediated via cortical and subcortical networks. At the cortical level, the superior frontal gyrus, including the supplementary motor area (SMA) and inferior frontal areas, is important. There is an ongoing debate about the functional roles of these structures during response inhibition as it is unclear whether these structures process different codes or contents of information during response inhibition. In the current study, we examined this question with a focus on theta frequency oscillations during response inhibition processes. We used a standard Go/Nogo task in a sample of human participants and combined different EEG signal decomposition methods with EEG beamforming approaches. The results suggest that stimulus coding during inhibitory control is attained by oscillations in the upper theta frequency band (∼7 Hz). In contrast, response selection codes during inhibitory control appear to be attained by the lower theta frequency band (∼4 Hz). Importantly, these different codes seem to be processed in distinct functional neuroanatomical structures. Although the SMA may process stimulus codes and response selection codes, the inferior frontal cortex may selectively process response selection codes during inhibitory control. Taken together, the results suggest that different entities within the functional neuroanatomical network associated with response inhibition mechanisms process different kinds of codes during inhibitory control. These codes seem to be reflected by different oscillations within the theta frequency band. Hum Brain Mapp 38:5681-5690, 2017. © 2017 Wiley-Liss, Inc.

Objective: The benefit of deep brain stimulation (DBS) for Parkinson's disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remains unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. Methods: A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of Unified Parkinson's Disease Rating Scale). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. Results: In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p

Background: Friedreich ataxia is characterized by progressive motor incoordination that is linked to peripheral, spinal, and cerebellar neuropathology. Cerebral abnormalities are also reported in Friedreich ataxia, but their role in disease expression remains unclear. Methods: In this cross-sectional functional magnetic resonance imaging study, 25 individuals with Friedreich ataxia and 33 healthy controls performed simple (self-paced single-finger) and complex (visually cued multifinger) tapping tasks to respectively gauge basic and attentionally demanding motor behavior. For each task, whole brain functional activations were compared between groups and correlated with disease severity and offline measures of motor dexterity. Results: During simple finger tapping, cerebral hyperactivation in individuals with Friedreich ataxia at the lower end of clinical severity and cerebral hypoactivation in those more severely affected was observed in premotor/ventral attention brain regions, including the supplementary motor area and anterior insula. Greater activation in this network correlated with greater offline finger tapping precision. Complex, attentionally demanding finger tapping was also associated with cerebral hyperactivation, but in this case within dorsolateral prefrontal regions of the executive control network and superior parietal regions of the dorsal attention system. Greater offline motor precision was associated with less activation in the dorsal attention network. Discussion: Compensatory activity is evident in the cerebral cortex in individuals with Friedreich ataxia. Early compensation followed by later decline in premotor/ventral attention systems demonstrates capacity-limited neural reserve, while the additional engagement of higher order brain networks is indicative of compensatory task strategies. Network-level changes in cerebral brain function thus potentially serve to mitigate the impact of motor impairments in Friedreich ataxia. © 2017 International Parkinson and Movement Disorder Society

We studied the neural mechanisms that are engaged during the experience of beauty derived from sorrow and from joy, two experiences that share a common denominator (beauty) but are linked to opposite emotional valences. Twenty subjects viewed and rerated, in a functional magnetic resonance imaging scanner, 120 images which each had classified into the following four categories: beautiful and sad; beautiful and joyful; neutral; ugly. The medial orbito-frontal cortex (mOFC) was active during the experience of both types of beauty. Otherwise, the two experiences engaged different parts of the brain: joyful beauty engaged areas linked to positive emotions while sorrowful beauty engaged areas linked to negative experiences. Separate regions of the cerebellum were engaged during experience of the two conditions. A functional connectivity analysis indicated that the activity within the mOFC was modulated by the supplementary motor area/middle cingulate cortex, known to be engaged during empathetic experiences provoked by other peoples' sadness. Hum Brain Mapp 38:4185-4200, 2017. © 2017 Wiley Periodicals, Inc.

SummaryAims To analyze brain functional connectivity in the somatomotor and default-mode networks (DMNs) of patients with Huntington disease (HD), its relationship with gray matter (GM) volume loss, and functional changes after pridopidine treatment. Methods Ten patients and ten untreated controls underwent T1-weighted imaging and resting-state functional magnetic resonance imaging (fMRI); four patients were also assessed after 3 months of pridopidine treatment (90 mg/d). The seed-based functional connectivity patterns from the posterior cingulate cortex and the supplementary motor area (SMA), considered cortical hubs of the DMN and somatomotor networks, respectively, were computed. FMRIB Software Library voxel-based morphometry measured GM volume. Results Patients had GM volume decrease in all cortical and subcortical areas of the somatomotor network with preservation of the SMA, and increased somatomotor and DMN connectivity. In DMN structures, functional connectivity impairment preceded volume loss. Pridopidine reduced the intensity of these aberrant connections. Conclusion The abnormal connectivity of the somatomotor and DMN observed in HD patients may represent an early dysfunction marker, as it preceded volume loss in DMN. Pridopidine reduced connectivity of these networks in all four treated patients, suggesting that connectivity is sensitive to treatment response.

The neuronal mechanisms underlying arithmetic calculations are not well understood but the differences between mental addition and subtraction could be particularly revealing. Using fMRI and dynamic causal modeling (DCM), this study aimed to identify the distinct neuronal architectures engaged by the cognitive processes of simple addition and subtraction. Our results revealed significantly greater activation during subtraction in regions along the dorsal pathway, including the left inferior frontal gyrus (IFG), middle portion of dorsolateral prefrontal cortex (mDLPFC), and supplementary motor area (SMA), compared with addition. Subsequent analysis of the underlying changes in connectivity - with DCM - revealed a common circuit processing basic (numeric) attributes and the retrieval of arithmetic facts. However, DCM showed that addition was more likely to engage (numeric) retrieval-based circuits in the left hemisphere, while subtraction tended to draw on (magnitude) processing in bilateral parietal cortex, especially the right intraparietal sulcus (IPS). Our findings endorse previous hypotheses about the differences in strategic implementation, dominant hemisphere, and the neuronal circuits underlying addition and subtraction. Moreover, for simple arithmetic, our connectivity results suggest that subtraction calls on more complex processing than addition: auxiliary phonological, visual, and motor processes, for representing numbers, were engaged by subtraction, relative to addition. Hum Brain Mapp 38:3210-3225, 2017. © 2017 Wiley Periodicals, Inc.

The contribution of the motor cortex to the semantic retrieval of verbs remains a subject of debate in neuroscience. Here, we examined whether additional engagement of the cortical motor system was required when access to verbs semantics was hindered during a verb generation task. We asked participants to produce verbs related to presented noun cues that were either strongly associated with a single verb to prompt fast and effortless verb retrieval, or were weakly associated with multiple verbs and more difficult to respond to. Using power suppression of magnetoencephalography beta oscillations (15–30 Hz) as an index of cortical activation, we performed a whole‐brain analysis in order to identify the cortical regions sensitive to the difficulty of verb semantic retrieval. Highly reliable suppression of beta oscillations occurred 250 ms after the noun cue presentation and was sustained until the onset of verbal response. This was localized to multiple cortical regions, mainly in the temporal and frontal lobes of the left hemisphere. Crucially, the only cortical regions where beta suppression was sensitive to the task difficulty, were the higher order motor areas on the medial and lateral surfaces of the frontal lobe. Stronger activation of the premotor cortex and supplementary motor area accompanied the effortful verb retrieval and preceded the preparation of verbal responses for more than 500 ms, thus, overlapping with the time window of verb retrieval from semantic memory. Our results suggest that reactivation of verb‐related motor plans in higher order motor circuitry promotes the semantic retrieval of target verbs.

Background and purpose We examined the resting-state functional connectivity (RSFC) of the supplementary motor area (SMA) in brain tumor patients. We compared the SMA subdivisions (pre-SMA, SMA proper, central SMA) in terms of RSFC projected from each region to the motor gyrus and language areas. Methods We retrospectively identified 14 brain tumor patients who underwent task-based and resting-state fMRI, and who completed motor and language paradigms that activated the SMA proper and pre-SMA, respectively. Regions of interest (ROIs) obtained from task-based fMRI were generated in both areas and the central SMA to produce RSFC maps. Degree of RSFC was measured from each subdivision to the motor gyrus and Broca's area (BA). Results All patients showed RSFC between the pre-SMA and language centers and between the SMA proper and motor gyrus. Thirteen of 14 patients showed RSFC from the central SMA to both motor and language areas. There was no significant difference between subdivisions in degree of RSFC to BA (pre-SMA, r = .801; central SMA, r = .803; SMA proper; r = .760). The pre-SMA showed significantly less RSFC to the motor gyrus (r = .732) compared to the central SMA (r = .842) and SMA proper (r = .883) (P = .016, P = .001, respectively). Conclusions The region between the pre-SMA and SMA proper produces reliable RSFC to the motor gyrus and language areas in brain tumor patients. This study is the first to examine RSFC of the central SMA in this population. Consequently, our results provide further validation to previous studies, supporting the existence of a central SMA with connectivity to both motor and language networks.

Background: Spasmodic dysphonia is a focal dystonia characterized by involuntary spasms in the laryngeal muscles that occur selectively during speaking. Although hereditary trends have been reported in up to 16% of patients, the causative etiology of spasmodic dysphonia is unclear, and the influences of various phenotypes and genotypes on disorder pathophysiology are poorly understood. In this study, we examined structural alterations in cortical gray matter and white matter integrity in relationship to different phenotypes and putative genotypes of spasmodic dysphonia to elucidate the structural component of its complex pathophysiology. Methods: Eighty-nine patients with spasmodic dysphonia underwent high-resolution magnetic resonance imaging and diffusion-weighted imaging to examine cortical thickness and white matter fractional anisotropy in adductor versus abductor forms (distinct phenotypes) and in sporadic versus familial cases (distinct genotypes). Results: Phenotype-specific abnormalities were localized in the left sensorimotor cortex and angular gyrus and the white matter bundle of the right superior corona radiata. Genotype-specific alterations were found in the left superior temporal gyrus, supplementary motor area, and the arcuate portion of the left superior longitudinal fasciculus. Conclusions: Our findings suggest that phenotypic differences in spasmodic dysphonia arise at the level of the primary and associative areas of motor control, whereas genotype-related pathophysiological mechanisms may be associated with dysfunction of regions regulating phonological and sensory processing. Identification of structural alterations specific to disorder phenotype and putative genotype provides an important step toward future delineation of imaging markers and potential targets for novel therapeutic interventions for spasmodic dysphonia.

Background The objective of this study was to investigate pedunculopontine nucleus network dysfunctions that mediate impaired postural control and sleep disorder in Parkinson's disease. Methods We examined (1) Parkinson's disease patients with impaired postural control and rapid eye movement sleep behavior disorder (further abbreviated as sleep disorder), (2) Parkinson's disease patients with sleep disorder only, (3) Parkinson's disease patients with neither impaired postural control nor sleep disorder, and (4) healthy volunteers. We assessed postural control with clinical scores and biomechanical recordings during gait initiation. Participants had video polysomnography, daytime sleepiness self-evaluation, and resting-state functional MRIs. Results Patients with impaired postural control and sleep disorder had longer duration of anticipatory postural adjustments during gait initiation and decreased functional connectivity between the pedunculopontine nucleus and the supplementary motor area in the locomotor network that correlated negatively with the duration of anticipatory postural adjustments. Both groups of patients with sleep disorder had decreased functional connectivity between the pedunculopontine nucleus and the anterior cingulate cortex in the arousal network that correlated with daytime sleepiness. The degree of dysfunction in the arousal network was related to the degree of connectivity in the locomotor network in all patients with sleep disorder, but not in patients without sleep disorder or healthy volunteers. Conclusions These results shed light on the functional neuroanatomy of pedunculopontine nucleus networks supporting the clinical manifestation and the interdependence between sleep and postural control impairments in Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society

Current theories of language recovery after stroke are limited by a reliance on small studies. Here, we aimed to test predictions of current theory and resolve inconsistencies regarding right hemispheric contributions to long-term recovery. We first defined the canonical semantic network in 43 healthy controls. Then, in a group of 43 patients with chronic post-stroke aphasia, we tested whether activity in this network predicted performance on measures of semantic comprehension, naming, and fluency while controlling for lesion volume effects. Canonical network activation accounted for 22%-33% of the variance in language test scores. Whole-brain analyses corroborated these findings, and revealed a core set of regions showing positive relationships to all language measures. We next evaluated the relationship between activation magnitudes in left and right hemispheric portions of the network, and characterized how right hemispheric activation related to the extent of left hemispheric damage. Activation magnitudes in each hemispheric network were strongly correlated, but four right frontal regions showed heightened activity in patients with large lesions. Activity in two of these regions (inferior frontal gyrus pars opercularis and supplementary motor area) was associated with better language abilities in patients with larger lesions, but poorer language abilities in patients with smaller lesions. Our results indicate that bilateral language networks support language processing after stroke, and that right hemispheric activations related to extensive left hemispheric damage occur outside of the canonical semantic network and differentially relate to behavior depending on the extent of left hemispheric damage. Hum Brain Mapp 38:1636-1658, 2017. © 2016 Wiley Periodicals, Inc.

Introduction Fatigue is a common problem in PD either in the early or later stage of the disease. Using resting-state functional MRI, we investigated the functional correlates of fatigue in a cohort of “drug-naive” patients with PD. Methods MRI at 3Tesla was collected in 40 patients with PD, 20 with and 20 without fatigue, and 20 matched healthy controls. Presence and the severity of fatigue were defined based on the 16-item Parkinson fatigue scale. Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major resting state networks between patients subgroups and healthy controls. In addition, we used voxel-based morphometry to test whether between-group functional changes were related to structural differences. Results Distressing fatigue was associated with a decreased connectivity in the supplementary motor area within the sensorimotor network and an increased connectivity in the prefrontal and posterior cingulate cortices within the default mode network (P < 0.05 corrected). Fatigue severity was correlated with both sensorimotor and default mode networks connectivity changes. Voxel-based morphometry analysis did not reveal any significant volume differences between all patients with PD and healthy controls and between patients with PD with and without fatigue (P < 0.05; family-wise error). Conclusions Our findings revealed that primary PD-related fatigue is associated with an altered default mode network and sensorimotor network connectivity in drug-naive patients. We hypothesize that these divergent motor and cognitive networks connectivity changes and their adaptive or maladaptive functional outcome may play a prominent role in the pathophysiology of fatigue in PD. © 2016 International Parkinson and Movement Disorder Society