Connectivity Of Supplementary Motor Area Research Articles

Cortical modulations before lower limb motor blocks are associated with freezing of gait in Parkinson’s disease: an EEG source localization study

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

Changes in Clinical and Network Functional Connectivity Parameters in Motor Networks and Cerebellum Based on Resting-State Functional Magnetic Resonance Imaging Data in Patients with Post-Stroke Hemiparesis Receiving Interactive Brain Stimulation Neurotherapy

Introduction. Interactive brain stimulation (IBS) neurotherapy is an advanced neurofeedback technology (NFB) that involves the organization of a feedback “target” based on signals recorded by functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). The NFB allows patients to volitionally self-regulate their current brain activity and may therefore be a useful treatment option for diseases with altered activation and functional connectivity (FC) patterns.
 Our objective was to assess the effects of IBS on the FC changes in motor networks and correlations between clinical and network parameters in patients with post-stroke hand paresis.
 Materials and methods. Patients with a history of stroke 2 months were randomized into a main group (n = 7) and a control group (n = 7). All the patients followed the stroke physical rehabilitation for 3 weeks. The main group received IBS training, where the patients learned to imagine movements of the paretic hand trying to amplify the fMRI signal from the primary motor cortex (M1) and the supplementary motor area (SMA) on the lesion side with simultaneous desynchronizing the μ- and β-2 EEG rhythms in the central leads. Clinical tests and MRI were performed prior to and immediately after the treatment. FC matrices were constructed using CONN software based on resting-state fMRI data.
 Results. By the end of the training, M1–M1 functional connectivity in the control group weakened, while no changes were observed in the main group. The FC strength was positively correlated with the grip strength (ρ = 0.69; p 0.01) and with the results of the Box and Blocks test (BBT score, ρ = 0.72; p 0.01) and the Fugl-Meyer assessment for upper extremity (FM-UE score, ρ = 0.87; p 0.005). Ipsilesional SMA connectivity with contralesional cerebellum weakened (p 0.05 in the main group). Its strength was negatively correlated with the BBT and FM-UE scores (both tests ρ = –0.44; p 0.05).
 Conclusions. Volitional control of M1 and SMA activity in the lesion hemisphere during the post-stroke IBS training alters the architecture of the entire motor network affecting clinically significant FC types. We studied a possible mechanism of this technology and its potential use in treatment programs.

Identifying the neurostimulation target for treatment of cognitive impairment in aging and early cerebral small vessel disease

To develop individualized approaches to the use of neuromodulation as a non-pharmacological treatment of cognitive impairment (CI) based on the assessment of compensatory brain reserves in functional MRI (fMRI). Twenty-one adults over 45 years of age, representing a continuum from healthy norm to mild cognitive impairment due to aging and early cerebral small vessel disease, were studied. All participants underwent fMRI while performing two executive tasks - a modified Stroop task and selective counting. To assess the ability to compensate for CI in real life, functional activation and connectivity were analyzed using the BRIEF-MoCA score as a covariate, which is the difference in ratings between the Behavior Rating Inventory of Executive Function (BRIEF) and the Montreal Cognitive Assessment Scale (MoCA). Both fMRI tasks were associated with activation of areas of the frontoparietal control network, as well as supplementary motor area (SMA) and the pre-SMA, the lateral premotor cortex, and the cerebellum. An increase in pre- SMA connectivity was observed during the tasks. The BRIEF-MoCA score correlated firstly with connectivity of the left dorsolateral prefrontal cortex (DLPFC) and secondly with involvement of the occipital cortex during the counting task. The developed technique allows identification of the functionally relevant target within the left DLPFC in patients with CI in aging and early cerebral microangiopathy.

Dynamic alternations of interhemispheric functional connectivity in brachial plexus avulsion injury patients with nerve transfer: a resting state fMRI study.

Brachial plexus avulsion injury (BPAI) is a severe peripheral nerve injury that leads to functional reorganization of the brain. However, the interhemispheric coordination following contralateral cervical 7 nerve transfer remains unclear. In this study, 69 BPAI patients underwent resting-state functional magnetic resonance imaging examination to assess the voxel-mirrored homotopic connectivity (VMHC), which reveals the interhemispheric functional connection. The motor function of the affected upper extremity was measured using the Fugl-Meyer Assessment of Upper Extremity (FMA-UE) scale. The VMHC analysis showed significant differences between the bilateral precentral gyrus, supplementary motor area (SMA), middle frontal gyrus (MFG), and insula. Compared to the preoperative group, the VMHC of the precentral gyrus significantly increased in the postoperative short-term group (PO-ST group) but decreased in the postoperative long-term group (PO-LT group). Additionally, the VMHC of the SMA significantly increased in the PO-LT group. Furthermore, the VMHC of the precentral gyrus in the PO-ST group and the SMA in the PO-LT group were positively correlated with the FMA-UE scores. These findings highlight a positive relationship between motor recovery and increased functional connectivity of precentral gyrus and SMA, which provide possible therapeutic targets for future neuromodulation interventions to improve rehabilitation outcomes for BPAI patients.

Role of supplementary motor area in cervical dystonia and sensory tricks.

Sensory trick is a characteristic feature of cervical dystonia (CD), where a light touch on the area adjacent to the dystonia temporarily improves symptoms. Clinical benefit from sensory tricks can be observed before tactile contact is made or even by imagination. The supplementary motor area (SMA) may dynamically interact with the sensorimotor network and other brain regions during sensory tricks in patients with CD. In this study, we examined the functional connectivity of the SMA at rest and during sensory trick performance and imagination in CD patients compared to healthy controls using functional magnetic resonance imaging. The functional connectivity between the SMA and left intraparietal sulcus (IPS) region was lower in CD patients at rest and it increased with sensory trick imagination and performance. SMA-right cerebellum connectivity also increased with sensory trick imagination in CD patients, while it decreased in healthy controls. In CD patients, SMA connectivity increased in the brain regions involved in sensorimotor integration during sensory trick performance and imagination. Our study results showed a crucial role of SMA in sensorimotor processing during sensory trick performance and imagination and suggest the IPS as a novel potential therapeutic target for brain modulation.

Aberrant functional connectivity within the salience network is related to cognitive deficits and disorganization in psychosis

In schizophrenia and schizoaffective disorder cognitive deficits are a reliable characteristic predicting a poor functional outcome. It has been theorized that both the default mode network (DMN) and the salience network (SN) play a crucial role in cognitive processes and aberrant functional connectivity within these networks in psychotic patients has been reported. The goal of this study was to reveal potential links between aberrant functional connectivity within these networks and impaired cognitive performance in psychosis.We chose two approaches for cognitive assessment, first the MATRICS Consensus Cognitive Battery (MCCB) combined into a global score and second the disorganization factor derived from a five-factor model of the Positive and Negative Syndrome Scale (PANSS) known to be relevant for cognitive performance. DMN and SN were identified using independent component analysis on resting-state functional magnetic resonance imaging data.We found significantly decreased connectivity within the right supplementary motor area (SMA) and bilateral putamen in patients with psychosis (n = 70; 27F/43M) compared to healthy controls (n = 72; 28F/44M). Within patients, linear regression analysis revealed that aberrant SMA connectivity was associated with impaired global cognition, while dysfunctional bilateral putamen connectivity predicted disorganization. There were no significant changes in connectivity within the DMN.Results support the hypothesis that SN dysfunctional connectivity is important in the pathobiology of cognitive deficits in psychosis. For the first time we were able to show the involvement of dysfunctional SMA connectivity in this context. We interpret the decreased SN connectivity as evidence of reduced functionality in recruiting brain areas necessary for cognitive processing.

Vitamin D and cardiometabolic outcomes in first episode psychosis (FEP): A prospective cohort study

In schizophrenia and schizoaffective disorder cognitive deficits are a reliable characteristic predicting a poor functional outcome. It has been theorized that both the default mode network (DMN) and the salience network (SN) play a crucial role in cognitive processes and aberrant functional connectivity within these networks in psychotic patients has been reported. The goal of this study was to reveal potential links between aberrant functional connectivity within these networks and impaired cognitive performance in psychosis.We chose two approaches for cognitive assessment, first the MATRICS Consensus Cognitive Battery (MCCB) combined into a global score and second the disorganization factor derived from a five-factor model of the Positive and Negative Syndrome Scale (PANSS) known to be relevant for cognitive performance. DMN and SN were identified using independent component analysis on resting-state functional magnetic resonance imaging data.We found significantly decreased connectivity within the right supplementary motor area (SMA) and bilateral putamen in patients with psychosis (n = 70; 27F/43M) compared to healthy controls (n = 72; 28F/44M). Within patients, linear regression analysis revealed that aberrant SMA connectivity was associated with impaired global cognition, while dysfunctional bilateral putamen connectivity predicted disorganization. There were no significant changes in connectivity within the DMN.Results support the hypothesis that SN dysfunctional connectivity is important in the pathobiology of cognitive deficits in psychosis. For the first time we were able to show the involvement of dysfunctional SMA connectivity in this context. We interpret the decreased SN connectivity as evidence of reduced functionality in recruiting brain areas necessary for cognitive processing.

Functional Connectivity of the Supplementary and Presupplementary Motor Areas in Postoperative Transition Between Stages of Frailty.

Frailty is a multietiological geriatric syndrome of run-down physical reserves with high vulnerability to stressors. Transitions between physical robustness and frailty often occur in the context of medical interventions. Studies suggest that neurological disorders contribute to faster progression of frailty. In a previous cross-sectional study we found altered functional connectivity of supplementary motor area (SMA) in (pre)frail compared to robust patients. We analyzed functional connectivity of the SMA and presupplementary motor area (pre-SMA) in patients with postoperative transitions between physical robustness and stages of frailty. We investigated 120 cognitively healthy patients (49.2% robust, 47.5% prefrail, 3.3% frail, 37.5% female, median age 71 [65-87] years) undergoing elective surgery from the BioCog project, a multicentric prospective cohort study on postoperative delirium and cognitive dysfunction. Assessments took place 14 days before and 3 months after surgery, comprising assessments of a modified frailty phenotype according to Fried and resting-state functional magnetic resonance imaging at 3 T. The associations between functional connectivity of the SMA and pre-SMA networks, preoperative frailty stages, and postoperative transitions were examined using mixed linear effects models. Nineteen patients showed physical improvement after surgery, 24 patients progressed to (pre)frailty and in 77 patients no transition was observed. At follow-up, 57 (47.5%) patients were robust, 52 (43.3%) prefrail, and 11 (9.2%) frail. Lower functional connectivity in the pre-SMA network was associated with more unfavorable postoperative transition types. An exploratory analysis suggested that the association was restricted to patients who were prefrail at baseline. There was no association of transition type with SMA functional connectivity in the primary analysis. In an exploratory analysis, transition from prefrailty to robustness was associated with higher functional connectivity and progression in robust patients was associated with higher SMA network segregation. Our findings implicate that dysfunctions of cortical networks involved in higher cognitive control of motion are associated with postoperative transitions between frailty stages. The pre-SMA may be a target for neurofeedback or brain stimulation in approaches to prevent frailty. Clinical Trials Registration Number: NCT02265263.

Global efficiency of the motor network is decreased in Parkinson's disease in comparison with essential tremor and healthy controls.

BackgroundGraph theory (GT) is a mathematical field that analyses complex networks that can be applied to neuroimaging to quantify brain's functional systems in Parkinson's disease (PD) and essential tremor (ET).ObjectivesTo evaluate the functional connectivity (FC) measured by the global efficiency (GE) of the motor network in PD and compare it to ET and healthy controls (HC), and correlate it to clinical parameters.Methods103 subjects (54PD, 18ET, 31HC) were submitted to structural and functional MRI. A network was designed with regions of interest (ROIs) involved in motor function, and GT was applied to determine its GE. Clinical parameters were analyzed as covariates to estimate the impact of disease severity and medication on GE.ResultsGE of the motor circuit was reduced in PD in comparison with HC (p .042). Areas that most contributed to it were left supplementary motor area (SMA) and bilateral postcentral gyrus. Tremor scores correlated positively with GE of the motor network in PD subgroups. For ET, there was an increase in the connectivity of the anterior cerebellar network to the other ROIs of the motor circuit in comparison with PD.ConclusionsFC measured by the GE of the motor network is diminished in PD in comparison with HC, especially due to decreased connectivity of left SMA and bilateral postcentral gyrus. This finding supports the theory that there is a global impairment of the motor network in PD, and it does not affect just the basal ganglia, but also areas associated with movement modulation. The ET group presented an increased connectivity of the anterior cerebellar network to the other ROIs of the motor circuit when compared to PD, which reinforces what it is known about its role in this pathology.

Paired inhibitory stimulation and gait training modulates supplemental motor area connectivity in freezing of gait

Freezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD). Evidence suggests patients with FOG have increased cortical control of gait. The supplementary motor area (SMA) may be a key structure due to its connectivity with locomotor and cognitive networks. The objectives of this study were to determine (1) if SMA connectivity is disrupted in patients with FOG and (2) if "inhibitory" repetitive transcranial magnetic stimulation can decrease maladaptive SMA connectivity. Two experiments were performed. In experiment 1 resting-state (T2* BOLD imaging) was compared between 38 PD freezers and 17 PD controls. In experiment 2, twenty PD patients with FOG were randomized to either 10 sessions of real or sham rTMS to the SMA (1Hz, 110% motor threshold, 1200 pulses/session) combined with daily gait training. (Experiment 1) Freezers had increased connectivity between the left SMA and the vermis of the cerebellum and decreased connectivity between the SMA and the orbitofrontal cortex (pFDR-corr <0.05). (Experiment 2) 10 sessions of active TMS reduced SMA connectivity with the anterior cingulate, angular gyrus and the medial temporal cortex, whereas sham TMS did not reduce SMA connectivity. From a behavioral perspective, both groups showed nFOG-Q improvements (F(4, 25.7)=3.87, p=0.014). The SMA in freezers is hyper-connected to the cerebellum, a key locomotor region which may represent maladaptive compensation. In this preliminary study, 1Hz rTMS reduced SMA connectivity however, this was not specific to the locomotor regions. Intervention outcomes may be improved with subject specific targeting of SMA.

Brain Plasticity Mechanisms Underlying Motor Control Reorganization: Pilot Longitudinal Study on Post-Stroke Subjects.

Functional Electrical Stimulation (FES) has demonstrated to improve walking ability and to induce the carryover effect, long-lasting persisting improvement. Functional magnetic resonance imaging has been used to investigate effective connectivity differences and longitudinal changes in a group of chronic stroke patients that attended a FES-based rehabilitation program for foot-drop correction, distinguishing between carryover effect responders and non-responders, and in comparison with a healthy control group. Bayesian hierarchical procedures were employed, involving nonlinear models at within-subject level—dynamic causal models—and linear models at between-subjects level. Selected regions of interest were primary sensorimotor cortices (M1, S1), supplementary motor area (SMA), and angular gyrus. Our results suggest the following: (i) The ability to correctly plan the movement and integrate proprioception information might be the features to update the motor control loop, towards the carryover effect, as indicated by the reduced sensitivity to proprioception input to S1 of FES non-responders; (ii) FES-related neural plasticity supports the active inference account for motor control, as indicated by the modulation of SMA and M1 connections to S1 area; (iii) SMA has a dual role of higher order motor processing unit responsible for complex movements, and a superintendence role in suppressing standard motor plans as external conditions changes.

Parcellation-based modeling of the supplementary motor area

IntroductionThe supplementary motor area (SMA) plays an important role in the initiation and coordination of internally and externally cued movements. Such movements include reaching, grasping, speaking, and bilateral hand coordination. While many studies discuss the SMA and its relationship to other parts of the motor network, there is minimal literature examining the connectivity of the SMA outside of the motor network. Using region-based fMRI studies, we built a neuroanatomical model to account for these extra-motor connections. MethodsThirty region-based fMRI studies were used to generate an activation likelihood estimation (ALE) using BrainMap software. Cortical parcellations overlapping the ALE were used to construct a preliminary model of the SMA connections outside the motor network. DSI-based fiber tractography was performed to determine the connectivity between cortical parcellations. The resulting connections were described using the cortical parcellation scheme developed by the Human Connectome Project (HCP). ResultsFour left hemisphere regions were found to comprise the SMA. These included areas SFL, SCEF, 6ma, and 6mp. Across mapped brains, these areas showed consistent interconnections between each other. Additionally, ipsilateral connections to the primary motor cortex, left inferior and middle frontal gyri, the anterior cingulate gyrus, and insula were demonstrated. Connections to the contralateral SMA, anterior cingulate, lateral premotor, and inferior frontal cortices were also identified. ConclusionsWe describe a preliminary cortical model for the underlying structural connectivity of the supplementary motor area outside the motor network. Future studies should further characterize the neuroanatomic underpinnings of this network for the purposes of medical application.

Cerebello-thalamo-cortical network is intrinsically altered in essential tremor: evidence from a resting state functional MRI study

Cerebello-thalamo-cortical network is suggested to be involved in the pathophysiology of Essential Tremor (ET). 23 patients with ET and 23 matched HC underwent a 3T-MRI with acquisition of a resting state sequence. Connectivity was investigated using a seed-based regression analyses approach. In ET patients were observed:Reduced connectivity between left primary motor cortex (M1) seed and right premotor cortex and cerebellum and bilateral premotor, parietal areas, supplementary motor area (SMA);Increased connectivity between left somatosensory cortex (S1) seed and parietal areas, M1, premotor cortex, SMA; reduced connectivity of this seed with cerebellum.Increased connectivity of SMA seed with premotor cortex and decreased with parietal and precentral areas;Increased connectivity between left thalamus seed and cerebellum;Reduced connectivity between right cerebellum seeds and other cerebellar areas, precentral and premotor areas.ET showed altered connectivity within the cortical sensory-motor network and between cerebral cortex and cerebellum. The increased connectivity between cerebellum and thalamus is consistent with their crucial role in tremor generation. These findings support the dynamical entrainment of multiple central oscillators throughout the cerebello-thalamo-cortical network in ET. This evidence is strengthened by the finding that this network is altered also when the core symptom is absent.

Resting-state functional connectivity of supplementary motor area associated with skin-picking symptom severity

Pathological skin picking (excoriation) is a relatively common disorder. Although it has been hypothesized to share a similar pathophysiological basis as other obsessive-compulsive (OC) spectrum disorders, to date, little work has specifically examined the precise neurobiological mechanisms involved in excoriation. Disruption in functional circuits involving the right inferior frontal gyrus (rIFG) and supplementary motor area (SMA) may be particularly relevant to skin-picking pathology as these regions have been implicated in other OC-spectrum disorders for their roles in response inhibition and voluntary motor action, respectively. To this end, the present study examined the associations between skin-picking symptom severity and resting-state functional connectivity of the rIFG and bilateral SMA. Participants endorsing elevated symptoms of excoriation completed a self-report measure of symptom severity and resting-state functional magnetic resonance imaging scan. Results indicated that symptom severity was associated with weaker connectivity between the SMA and clusters within the orbitofrontal cortex and angular gyrus. Contrary to hypotheses, there were no effects of symptom severity on functional connectivity of the rIFG. Overall, these findings suggest that skin-picking symptom severity may be associated with disruption in higher-order motor networks contributing to deficits in top-down regulation of motor behavior.

Predicting Long-Term After-Effects of Theta-Burst Stimulation on Supplementary Motor Network Through One-Session Response.

To understand the neural mechanism of repetitive transcranial magnetic stimulation (rTMS), the after-effects following one session or multiple days of stimulation have been widely investigated. However, the relation between the short-term effect (STE) and long-term effect (LTE) of rTMS is largely unknown. This study aims to explore whether the after-effects of 5-day rTMS on supplementary motor area (SMA) network could be predicted by one-session response. A primary cohort of 38 healthy participants underwent five daily sessions of real or sham continuous theta-burst stimulation (cTBS) on the left SMA. Resting-state functional magnetic resonance imaging (fMRI) data were acquired at the first (before and after the first stimulation) and sixth experimental day. The SMA connectivity changes after the first cTBS and after 5 days of stimulation were defined as STE and LTE, respectively. Compared to the baseline, significant STE and LTE were found in the bilateral paracentral gyrus (ParaCG) after real stimulation, suggesting shared neural correlates of short- and long-term stimulations. Region-of-interest analysis indicated that the resting-state functional connectivity between SMA and ParaCG increased after real stimulation, while no significant change was found after sham stimulation. Leave-one-out cross-validation indicated that the LTE in ParaCG could be predicted by the STE after real but not sham stimulations. In an independent cohort, the after-effects of rTMS on ParaCG and short- to long-term prediction were reproduced at the region-of-interest level. These imaging evidences indicate that one-session rTMS can aid to predict the regions responsive to long-term stimulation and the individualized response degree.

Functional connectivity of supplementary motor area during finger-tapping in major depression

Psychomotor disturbance has been consistently regarded as an essential feature of depressive disorders. Studying objectively measurable motor behaviors like finger-tapping may help advance the diagnostic methods.Twenty-five patients with major depressive disorder (MDD) and 15 healthy participants underwent functional magnetic resonance imaging (fMRI) measurements while tapping their index fingers. The finger-tapping (FT) task was performed by the right hand (the tapping frequency varied between 1, 2 and 4 Hz) or both hands either in synchrony or alternation (the tapping frequency varied between 1 and 2 Hz). A mixed-model ANOVA was used for between- and within-group comparisons of the task accuracy and fMRI percent signal change in the supplementary motor area (SMA) during 26-second sequences of finger-tapping. Furthermore, using seed-based correlation analyses we compared the connectivity of the SMA between the two samples.At the behavioral level, no significant group differences in FT performance between the patient and control groups was observed. The mean fMRI percent signal change of the SMA was significantly elevated at higher levels of speed in both groups. In the MDD group, an increased connectivity of the left SMA with the bilateral cortical and cerebellar motor- and vision-related regions was found. Most importantly, a decreased connectivity between the SMA and the basal ganglia was found at frequencies of 4 Hz.Our findings support the contention that, in depression, brain connectivity measures during motor performance may reveal deviant neural processes that are potentially relevant to measurable (bio)markers for individual diagnosis and treatment.

Sex Effect on Presurgical Language Mapping in Patients With a Brain Tumor.

Differences between males and females in brain development and in the organization and hemispheric lateralization of brain functions have been described, including in language. Sex differences in language organization may have important implications for language mapping performed to assess, and minimize neurosurgical risk to, language function. This study examined the effect of sex on the activation and functional connectivity of the brain, measured with presurgical functional magnetic resonance imaging (fMRI) language mapping in patients with a brain tumor. We carried out a retrospective analysis of data from neurosurgical patients treated at our institution who met the criteria of pathological diagnosis (malignant brain tumor), tumor location (left hemisphere), and fMRI paradigms [sentence completion (SC); antonym generation (AG); and resting-state fMRI (rs-fMRI)]. Forty-seven patients (22 females, mean age = 56.0 years) were included in the study. Across the SC and AG tasks, females relative to males showed greater activation in limited areas, including the left inferior frontal gyrus classically associated with language. In contrast, males relative to females showed greater activation in extended areas beyond the classic language network, including the supplementary motor area (SMA) and precentral gyrus. The rs-fMRI functional connectivity of the left SMA in the females was stronger with inferior temporal pole (TP) areas, and in the males with several midline areas. The findings are overall consistent with theories of greater reliance on specialized language areas in females relative to males, and generalized brain areas in males relative to females, for language function. Importantly, the findings suggest that sex could affect fMRI language mapping. Thus, considering sex as a variable in presurgical language mapping merits further investigation.

REAL-TIME BIOFEEDBACK INTEGRATED INTO NEUROMUSCULAR TRAINING INCREASES BRAIN FUNCTIONAL CONNECTIVITY AND REDUCES HIGH-RISK KNEE BIOMECHANICS

Background: Anterior cruciate ligament (ACL) injury is associated with alterations in the central nervous system and resultant sensorimotor control (Courtney et al., 2005; Grooms et al., 2017). Our prospective data indicates that altered knee-motor functional brain connectivity is associated with increased risk for ACL injury (Diekfuss et al., revisions invited), revealing novel neural targets for neuromuscular training interventions. Specifically, interventions that integrate concomitant sensorimotor feedback with injury prevention techniques have the potential to enhance brain functional connectivity to optimize ACL injury risk reduction strategies. To deliver concomitant sensorimotor feedback, we have developed an augmented neuromuscular training (aNMT) system that utilizes interactive, real-time biofeedback to simultaneously target multiple biomechanical variables associated with ACL injury risk (Bonnette et al., in press; Figure 1A). aNMT calculates and maps key biomechanical parameters to an interactive graphical shape that responds in real time as a function of participants’ movements. Participants are instructed to perform exercises to achieve a goal shape, which equates to producing biomechanical parameters associated with ACL injury risk reduction, while deviations toward injury risk factors result in specific shape distortions. We hypothesized that aNMT would significantly improve biomechanics associated with ACL injury risk and also increase knee-motor functional connectivity. We further predicted that the identified connectivity changes would be associated with the hypothesized changes in biomechanics. Methods: Over six weeks of training, participants (n = 25) performed a series of aNMT-based progressive exercises (e.g., squat, overhead squat, squat jump, tuck jump, single-leg Romanian dead lift, pistol squat) and completed a drop vertical jump (DVJ) task while fully instrumented for 3D motion analysis pre- and post-training. Peak knee abduction moment (pKAM; bilateral average) from the DVJ was used as the biomechanical outcome variable. Resting-state functional magnetic resonance imaging (fMRI) scans were also collected pre- and post-training on a subset of the cohort (n = 17). Thirteen additional participants were recruited to serve as untrained controls and completed the DVJ and resting-state fMRI on two testing sessions separated by approximately 6 weeks. Twenty-five knee-motor regions of interest (ROIs) were created based on the areas of brain activation derived from previously published data (Grooms et al., 2015; Kapreli et al., 2007). Paired-samples t tests with a false discovery rate correction for multiple comparisons determined differences in functional connectivity among these 25 ROIs (post &gt; pre). Fisher-transformed Pearson correlation coefficients between the average residual blood oxygen level dependent (BOLD) signal time series extracted from ROIs that demonstrated significant group level changes were associated with pKAM in DVJ task at pre- and post-training. The pre- and post-training Pearson correlation coefficients were subsequently compared using the cocor package (Diedenhofen &amp; Musch, 2015) to determine if the two relationships were significantly different. Results: Results showed that pKAM in the aNMT group was significantly lower following aNMT (p &lt; .05), while no significant changes were found between the two time points for controls (p &gt; .05). Results also revealed significantly greater functional connectivity between the right supplementary motor area (SMA) and the left thalamus at post-training relative to pre-training for the aNMT group, t(16) = 3.37, p = .04 (Figure 1B). No significant differences between the two time points were observed for the controls (all p &gt; .05). The association between pKAM and the right SMA and left thalamus at pre-training (r = -.22; Figure 1C) was significantly different compared to that at post-training (r = .26; Figure 1D), p &lt; .05, with a positive relationship between pKAM and SMA and thalamus activation following aNMT biofeedback. No similar changes in pKAM and right SMA and left thalamus connectivity were observed for the untrained controls, p &gt; .05. Conclusions/Significance: The right SMA is involved in the planning and coordination of movement, and the left thalamus is associated with neuromotor control. The increased functional connectivity between these regions, combined with the reduction in pKAM, which is associated with reduced risk of ACL injury, indicate a possible neural mechanism for improved motor adaption associated with aNMT biofeedback. These findings have distinct implications for ACL injury prevention strategies. Biofeedback tools such as aNMT can be designed to target specifically the neural drivers of aberrant movement biomechanics underlying increased ACL injury risk. [Figure: see text]

Supplementary motor area connectivity and dual-task walking variability in multiple sclerosis

BackgroundDespite 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 methodsAll 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. ResultsEighteen 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. ConclusionsThe 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.

Face perception enhances insula and motor network reactivity in Tourette syndrome.

Tourette syndrome is a neurodevelopmental disorder, characterized by motor and phonic tics. Tics are typically experienced as avolitional, compulsive, and associated with premonitory urges. They are exacerbated by stress and can be triggered by external stimuli, including social cues like the actions and facial expressions of others. Importantly, emotional social stimuli, with angry facial stimuli potentially the most potent social threat cue, also trigger behavioural reactions in healthy individuals, suggesting that such mechanisms may be particularly sensitive in people with Tourette syndrome. Twenty-one participants with Tourette syndrome and 21 healthy controls underwent functional MRI while viewing faces wearing either neutral or angry expressions to quantify group differences in neural activity associated with processing social information. Simultaneous video recordings of participants during neuroimaging enabled us to model confounding effects of tics on task-related responses to the processing of faces. In both Tourette syndrome and control participants, face stimuli evoked enhanced activation within canonical face perception regions, including the occipital face area and fusiform face area. However, the Tourette syndrome group showed additional responses within the anterior insula to both neutral and angry faces. Functional connectivity during face viewing was then examined in a series of psychophysiological interactions. In participants with Tourette syndrome, the insula showed functional connectivity with a set of cortical regions previously implicated in tic generation: the presupplementary motor area, premotor cortex, primary motor cortex, and the putamen. Furthermore, insula functional connectivity with the globus pallidus and thalamus varied in proportion to tic severity, while supplementary motor area connectivity varied in proportion to premonitory sensations, with insula connectivity to these regions increasing to a greater extent in patients with worse symptom severity. In addition, the occipital face area showed increased functional connectivity in Tourette syndrome participants with posterior cortical regions, including primary somatosensory cortex, and occipital face area connectivity with primary somatosensory and primary motor cortices varied in proportion to tic severity. There were no significant psychophysiological interactions in controls. These findings highlight a potential mechanism in Tourette syndrome through which heightened representation within insular cortex of embodied affective social information may impact the reactivity of subcortical motor pathways, supporting programmed motor actions that are causally implicated in tic generation. Medicinal and psychological therapies that focus on reducing insular hyper-reactivity to social stimuli may have potential benefit for tic reduction in people with Tourette syndrome.