Primary Motor Cortex Area Research Articles

P 16 The implementation of Near-Infrared-Spectroscopy (NIRS) in sports science – a verification of suitability using the compound movement squat

Introduction Near - Infrared Spectroscopy (NIRS) serves as a promising tool to examine cortical activity in a sports-scientific context. The associated feasibility of said method remains to be validated as exercise - induced confounders such as increases in extracerebral blood flow have been postulated ( Tachtsidis and Scholkmann, 2016 ). Additionally, the relationship between force and cortical activity is yet to be investigated in compound movements. Both parameters show a linear relationship in isolated movements ( Shibuya et al., 2014 ) yet it remains unclear whether this relationship applies to compound movements. Here we assessed the feasibility of NIRS for the compound movement barbell squat (BS). Complementarily the relationship between force levels and cortical activity during the squat was examined. We hypothesized that the extracerebral blood flow superimposes the signal and can be eliminated. Furthermore, we hypothesized a linear relationship between force during BS and cortical activity in the leg area of bilateral primary motor cortex (M1). Methods Ten healthy young adults participated in this study (n = 10; age: 25.7 ± 2.214 years). All subjects performed the BS task, five 90° squats per activity block, on three separate days with varying NIRS - configurations to control for and eliminate extracerebral effects. The experimental setup corresponds to a block design with varying force levels (L0%, L20%, L40%) which were individually adjusted in succession to Maximum Strength Tests. Our standard NIRS - configuration (A) covered the cortical motor system. The second configuration (B) additionally covered bilateral auditory cortices, frontopolar areas, as well as primary visual cortex. A third configuration incorporated a short - distance - channel to use this channel in a short separation regression (C). Cortical activation was assumed to be reflected by increased oxyhemoglobin (HbO2) and a corresponding decline or unchanged deoxyhemoglobin (HHb). Results For (A) and (B), HbO2showed a significant increase in the entire detection range when comparing the varying force levels during BS ( p 0.0023 ). For (C), HbO2 showed a significant increase in bilateral superior parietal lobule (SPL) (L20%, L40%) when compared to L0% ( p 0.01 ). HbO2 showed no significant increase when comparing the different force levels to baseline values. HHb showed no regionally consistent, significant decline for all comparisons. Discussion Short separation regression potentially enables the disentanglement of extracerebral blood flow from cerebral blood flow. There is a relationship between force and cortical activity in the squat when comparing force levels, although in bilateral SPL as opposed to M1 as seen in isolated movements. This implies a different modulator for compound movements compared to isolated movements.

The motor cortical representation of a muscle is not homogeneous in brain connectivity.

Functional connectivity patterns of the motor cortical representational area of single muscles have not been extensively mapped in humans, particularly for the axial musculature. Functional connectivity may provide a neural substrate for adaptation of muscle activity in axial muscles that have both voluntary and postural functions. The purpose of this study was to combine brain stimulation and neuroimaging to both map the cortical representation of the external oblique (EO) in primary motor cortex (M1) and supplementary motor area (SMA), and to establish the resting-state functional connectivity associated with this representation. Motor-evoked potentials were elicited from the EO muscle in stimulation locations encompassing M1 and SMA. The coordinates of locations with the largest motor-evoked potentials were confirmed with task-based fMRI imaging during EO activation. The M1 and SMA components of the EO representation demonstrated significantly different resting-state functional connectivity with other brain regions: the SMA representation of the EO muscle was significantly more connected to the putamen and cerebellum, and the M1 representation of the EO muscle was significantly more connected to somatosensory cortex and the superior parietal lobule. This study confirms the representation of a human axial muscle in M1 and SMA, and demonstrates for the first time that different parts of the cortical representation of a human axial muscle have resting-state functional connectivity with distinct brain regions. Future studies can use the brain regions of interest we have identified here to test the association between resting-state functional connectivity and control of the axial muscles.

Efficacy of transcranial direct current stimulation over primary motor cortex (anode) and contralateral supraorbital area (cathode) on clinical pain severity and mobility performance in persons with knee osteoarthritis: An experimenter- and participant-blinded, randomized, sham-controlled pilot clinical study

BackgroundPrevious studies indicate that transcranial direct current stimulation (tDCS) with anode over motor cortex (M1) and cathode over contralateral supraorbital region (SO) may be effective in reducing pain, but these studies are limited in number and have not focused on older adults with osteoarthritis (OA). ObjectiveTo evaluate the preliminary efficacy and safety of M1-SO applied tDCS on clinical pain severity and mobility performance in adults with knee OA pain. MethodsForty 50- to 70-year-old community-dwelling participants with knee OA were randomly assigned to receive five daily sessions of 2 mA tDCS for 20 min (n = 20) or sham tDCS (n = 20). We measured clinical pain severity via Numeric Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Short-Form McGill Pain Questionnaire. In addition, we measured mobility performance using the 6-Minute Walk Test and the Short Physical Performance Battery. Moreover, we obtained a sensation/safety questionnaire and measured cognition changes using the PROMIS-Applied Cognition-Abilities-Short Form 8a. ResultsActive tDCS over M1-SO significantly reduced Numeric Rating Scale of pain compared to sham tDCS after completion of the five daily sessions, and remained up to three weeks. No other measures were significantly different from sham. Participants tolerated tDCS over M1-SO well without serious adverse effects or cognition changes. ConclusionAlthough not consistent in all pain measurements, our findings demonstrate promising clinical efficacy for reduction in pain perception for older adults with knee OA. Trial registrationClinicalTrials.gov Identifier NCT02512393.

T002 Non-invasive brain stimulation for Parkinson’s disease

In advanced Parkinson’s disease (PD), the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation(DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, though whether a causal interaction exists remains largely undetermined. Most trials of non-invasive brain stimulation in PD have applied repetitive trans-cranial magnetic stimulation(rTMS) targeting the primary motor cortex and cortical areas of the motor circuit. The current studies suggest a possible therapeutic potential of rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible regarding functional independence and quality of life. Approaches to potentiate the efficacy of rTMS include increasing stimulation intensity and novel stimulation parameters, which derive their rationale from studies on brain physiology. These novel parameters intend to simulate normal firing patterns or to act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia in motor control and its contribution to the pathogenesis of motor disorders. There may be a diagnostic potential of TMS in better characterizing individual traits in the perspective of personalized medicine.

Abstract WP112: Residual Damage is Reduced Following Human Umbilical Tissue Derived Cell Infusion in a Non-human Primate Model of Cortical Injury

Introduction: Stroke is the leading cause of long-term disability in the United States due to impairments that endure after brain injury. While studies in rodent models have evaluated numerous neurorestorative treatments following stroke, none have received FDA approval. We evaluated a therapy using human umbilical tissue-derived cells (hUTC) as a potential neurorestorative treatment in our non-human primate model of cortical injury limited to the hand area of primary motor cortex. Given treatment 24 hours after injury, hUTC treated monkeys showed a significantly greater degree of recovery of fine motor function compared to vehicle treated controls (Moore et al., 2013). To explore the effect of hUTC, histopathological markers of inflammation and oxidative stress were assessed. Hypothesis: Treatment with hUTC will enhance the recruitment of glia to the injury and reduce the cascade of inflammation and oxidative stress. Methods: Using immunohistochemistry, activated microglia (LN3), reactive astrocytes (GFAP), oxidative damage (4HNE), and accumulated hemosiderin (Perls’ Prussian Blue) were quantified in ipsilesional primary motor cortex and underlying white matter. Microglia were counted using unbiased stereology. A Sholl Analysis was performed on traced perilesional astrocytes. The area of oxidative damage and hemosiderin was assessed using densitometry. Results: Compared to vehicle controls, density of activated microglia in the hUTC treated group approached a significant increase in the perilesional gray and white matter (p=0.070; p=0.092). Astrocytes exhibited more complex processes in treated monkeys (p=0.042). Staining for 4HNE was significantly reduced in white matter underlying the lesion in treated monkeys (p=0.033). Lastly, both the area and intensity of Perls’ staining for hemosiderin was significantly reduced in the perilesional area of treated monkeys (p=0.045; p=0.001). Conclusions: Treatment with hUTC resulted in increased activation of microglia and complexity of reactive astrocyte processes as well as reduced post-lesion oxidative damage and hemosiderin deposition. This suggests the hUTC treatment enhanced recovery, in part, by recruitment of glial cells that limited the damage following cortical injury.

The role of hearing ability and speech distortion in the facilitation of articulatory motor cortex

Excitability of articulatory motor cortex is facilitated when listening to speech in challenging conditions. Beyond this, however, we have little knowledge of what listener-specific and speech-specific factors engage articulatory facilitation during speech perception. For example, it is unknown whether speech motor activity is independent or dependent on the form of distortion in the speech signal. It is also unknown if speech motor facilitation is moderated by hearing ability. We investigated these questions in two experiments. We applied transcranial magnetic stimulation (TMS) to the lip area of primary motor cortex (M1) in young, normally hearing participants to test if lip M1 is sensitive to the quality (Experiment 1) or quantity (Experiment 2) of distortion in the speech signal, and if lip M1 facilitation relates to the hearing ability of the listener. Experiment 1 found that lip motor evoked potentials (MEPs) were larger during perception of motor-distorted speech that had been produced using a tongue depressor, and during perception of speech presented in background noise, relative to natural speech in quiet. Experiment 2 did not find evidence of motor system facilitation when speech was presented in noise at signal-to-noise ratios where speech intelligibility was at 50% or 75%, which were significantly less severe noise levels than used in Experiment 1. However, there was a significant interaction between noise condition and hearing ability, which indicated that when speech stimuli were correctly classified at 50%, speech motor facilitation was observed in individuals with better hearing, whereas individuals with relatively worse but still normal hearing showed more activation during perception of clear speech. These findings indicate that the motor system may be sensitive to the quantity, but not quality, of degradation in the speech signal. Data support the notion that motor cortex complements auditory cortex during speech perception, and point to a role for the motor cortex in compensating for differences in hearing ability.

Neural correlates of motor recovery after robot-assisted stroke rehabilitation: a case series study

ABSTRACTRobot-assisted bilateral arm therapy (RBAT) has shown promising results in stroke rehabilitation; however, connectivity mapping of the sensorimotor networks after RBAT remains unclear. We used fMRI before and after RBAT and a dose-matched control intervention (DMCI) to explore the connectivity changes in 6 subacute stroke patients. Sensorimotor functions improved in the RBAT and DMCI groups after treatment. Enhanced activation changes were observed in bilateral primary motor cortex (M1) and bilateral supplementary motor area (SMA) after RBAT. Dynamic causal model analysis revealed that interhemispheric connections were enhanced in RBAT patients. These preliminary findings suggest that intracortical and intercortical coupling might underlie poststroke RBAT.

Mirror Neurons System Engagement in Late Adolescents and Adults While Viewing Emotional Gestures.

Observing others’ actions enhances muscle-specific cortico-spinal excitability, reflecting putative mirror neurons activity. The exposure to emotional stimuli also modulates cortico-spinal excitability. We investigated how those two phenomena might interact when they are combined, i.e., while observing a gesture performed with an emotion, and whether they change during the transition between adolescence and adulthood, a period of social and brain maturation. We delivered single-pulse transcranial magnetic stimulation (TMS) over the hand area of the left primary motor cortex of 27 healthy adults and adolescents and recorded their right first dorsal interossus (FDI) muscle activity (i.e., motor evoked potential – MEP), while they viewed either videos of neutral or angry hand actions and facial expressions, or neutral objects as a control condition. We reproduced the motor resonance and the emotion effects – hand-actions and emotional stimuli induced greater cortico-spinal excitability than the faces/control condition and neutral videos, respectively. Moreover, the influence of emotion was present for faces but not for hand actions, indicating that the motor resonance and the emotion effects might be non-additive. While motor resonance was observed in both groups, the emotion effect was present only in adults and not in adolescents. We discuss the possible neural bases of these findings.

Motor recovery at 6 months after admission is related to structural and functional reorganization of the spine and brain in patients with spinal cord injury.

This study aimed to explore structural and functional reorganization of the brain in the early stages of spinal cord injury (SCI) and identify brain areas that contribute to motor recovery. We studied 25 patients with SCI, including 10 with good motor recovery and 15 with poor motor recovery, along with 25 matched healthy controls. The mean period post-SCI was 9.2 ± 3.5 weeks in good recoverers and 8.8 ± 2.6 weeks in poor recoverers. All participants underwent structural and functional MRI on a 3-T magnetic resonance system. We evaluated differences in cross-sectional spinal cord area at the C2/C3 level, brain cortical thickness, white matter microstructure, and functional connectivity during the resting state among the three groups. We also evaluated associations between structural and functional reorganization and the rate of motor recovery. After SCI, compared with good recoverers, poor recoverers had a significantly decreased cross-sectional spinal cord area, cortical thickness in the right supplementary motor area and premotor cortex, and fractional anisotropy (FA) in the right primary motor cortex and posterior limb of the internal capsule. Meanwhile, poor recoverers showed decreased functional connectivity between the primary motor cortex and higher order motor areas (supplementary motor area and premotor cortex), while good recoverers showed increased functional connectivity among these regions. The structural and functional reorganization of the spine and brain was associated with motor recovery rate in all SCI patients. In conclusion, structural and functional reorganization of the spine and brain directly affected the motor recovery of SCI. Less structural atrophy and enhanced functional connectivity are associated with good motor recovery in patients with SCI. Multimodal imaging has the potential to predict motor recovery in the early stage of SCI. Hum Brain Mapp 37:2195-2209, 2016. © 2016 Wiley Periodicals, Inc.

Effects of an Exhaustive Exercise on Motor Skill Learning and on the Excitability of Primary Motor Cortex and Supplementary Motor Area.

We examined, on 28 healthy adult subjects, the possible correlations of an exhaustive exercise, and the consequent high blood lactate levels, on immediate (explicit) and delayed (implicit) motor execution of sequential finger movements (cognitive task). Moreover, we determined with transcranial magnetic stimulation whether changes in motor performance are associated with variations in excitability of primary motor area (M1) and supplementary motor area (SMA). We observed that, after an acute exhaustive exercise, the large increase of blood lactate is associated with a significant worsening of both explicit and implicit sequential visuomotor task paradigms, without gender differences. We also found that, at the end of the exhaustive exercise, there is a change of excitability in both M1 and SMA. In particular, the excitability of M1 was increased whereas that of SMA decreased and, also in this case, without gender differences. These results support the idea that an increase of blood lactate after an exhaustive exercise appears to have a protective effect at level of primary cortical areas (as M1), although at the expense of efficiency of adjacent cortical regions (as SMA).

Altered Spontaneous Brain Activity in Betel Quid Dependence: A Resting-state Functional Magnetic Resonance Imaging Study.

It has been suggested by the first voxel-based morphometry investigation that betel quid dependence (BQD) individuals are presented with brain structural changes in previous reports, and there may be a neurobiological basis for BQD individuals related to an increased risk of executive dysfunction and disinhibition, subjected to the reward system, cognitive system, and emotion system. However, the effects of BQD on neural activity remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered spontaneous cerebral activity in resting-state functional magnetic resonance imaging and those changes are usually earlier than structural alteration.Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an resting-state functional magnetic resonance imaging study to observe brain function alterations associated with the severity of BQD. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were both evaluated to stand for spontaneous cerebral activity. Gray matter volumes of these participants were also calculated for covariate.In comparison with healthy controls, BQD individuals demonstrated dramatically decreased ALFF and ReHo values in the prefrontal gurus along with left fusiform, and increased ALFF and ReHo values in the primary motor cortex area, temporal lobe as well as some regions of occipital lobe. The betel quid dependence scores (BQDS) were negatively related to decreased activity in the right anterior cingulate.The abnormal spontaneous cerebral activity revealed by ALFF and ReHo calculation excluding the structural differences in patients with BQD may help us probe into the neurological pathophysiology underlying BQD-related executive dysfunction and disinhibition. Diminished spontaneous brain activity in the right anterior cingulate cortex may, therefore, represent a biomarker of BQD individuals.

Novel role for transcranial magnetic stimulation to study post-traumatic respiratory neuroplasticity.

Transcranial magnetic stimulation-a tool used in humans: Transcranial magnetic stimulation (TMS) is a non-invasive widespread clinical tool used to stimulate cortical areas in human subjects. This technique utilizes a brief, highly intense magnetic field applied to cortical areas, which locally depolarized interneurons (Weber and Eisen, 2002). When applied to primary motor cortex areas, TMS induces volleys of action potentials which propagate along corticospinal pathways from supraspinal levels to their muscular targets where motor evoked potentials (MEP) can be recorded. Accordingly, MEP amplitude and latency values provide good indexes of corticospinal pathway integrity or alterations.

Analysis of Time-Dependent Brain Network on Active and MI Tasks for Chronic Stroke Patients.

Several researchers have analyzed brain activities by investigating brain networks. However, there is a lack of the research on the temporal characteristics of the brain network during a stroke by EEG and the comparative studies between motor execution and imagery, which became known to have similar motor functions and pathways. In this study, we proposed the possibility of temporal characteristics on the brain networks of a stroke. We analyzed the temporal properties of the brain networks for nine chronic stroke patients by the active and motor imagery tasks by EEG. High beta band has a specific role in the brain network during motor tasks. In the high beta band, for the active task, there were significant characteristics of centrality and small-worldness on bilateral primary motor cortices at the initial motor execution. The degree centrality significantly increased on the contralateral primary motor cortex, and local efficiency increased on the ipsilateral primary motor cortex. These results indicate that the ipsilateral primary motor cortex constructed a powerful subnetwork by influencing the linked channels as compensatory effect, although the contralateral primary motor cortex organized an inefficient network by using the connected channels due to lesions. For the MI task, degree centrality and local efficiency significantly decreased on the somatosensory area at the initial motor imagery. Then, there were significant correlations between the properties of brain networks and motor function on the contralateral primary motor cortex and somatosensory area for each motor execution/imagery task. Our results represented that the active and MI tasks have different mechanisms of motor acts. Based on these results, we indicated the possibility of customized rehabilitation according to different motor tasks. We expect these results to help in the construction of the customized rehabilitation system depending on motor tasks by understanding temporal functional characteristics on brain network for a stroke.

Brain structural and functional connectivity in Parkinson's disease with freezing of gait.

To use a multimodal approach to assess brain structural pathways and resting state (RS) functional connectivity abnormalities in patients with Parkinson's disease and freezing of gait (PD-FoG). T1-weighted, diffusion tensor (DT) MRI and RS functional MRI (fMRI) were obtained from 22 PD-FoG patients and 35 controls on a 3.0 T MR scanner. Patients underwent clinical, motor, and neuropsychological evaluations. Gray matter (GM) volumes and white matter (WM) damage were assessed using voxel based morphometry and tract-based spatial statistics, respectively. The pedunculopontine tract (PPT) was studied using tractography. RS fMRI data were analyzed using a model free approach investigating the main sensorimotor and cognitive brain networks. Multiple regression models were performed to assess the relationships between structural, functional, and clinical/cognitive variables. Analysis of GM and WM structural abnormalities was replicated in an independent sample including 28 PD-FoG patients, 25 PD patients without FoG, and 30 healthy controls who performed MRI scans on a 1.5 T scanner. Compared with controls, no GM atrophy was found in PD-FoG cases. PD-FoG patients showed WM damage of the PPT, corpus callosum, corticospinal tract, cingulum, superior longitudinal fasciculus, and WM underneath the primary motor, premotor, prefrontal, orbitofrontal, and inferior parietal cortices, bilaterally. In PD-FoG, right PTT damage was associated with a greater disease severity. Analysis on the independent PD sample showed similar findings in PD-FoG patients relative to controls as well as WM damage of the genu and body of the corpus callosum and right parietal WM in PD-FoG relative to PD no-FoG patients. RS fMRI analysis showed that PD-FoG is associated with a decreased functional connectivity of the primary motor cortex and supplementary motor area bilaterally in the sensorimotor network, frontoparietal regions in the default mode network, and occipital cortex in the visual associative network. This study suggests that FoG in PD can be the result of a poor structural and functional integration between motor and extramotor (cognitive) neural systems.

Non-invasive brain stimulation for Parkinson's disease: Current concepts and outlook 2015.

In advanced Parkinson's disease (PD), the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, though whether a causal interaction exists remains largely undetermined. Most trials of non-invasive brain stimulation in PD have applied repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex and cortical areas of the motor circuit. Published studies suggest a possible therapeutic potential of rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible regarding functional independence and quality of life. Approaches to potentiate the efficacy of rTMS, including increasing stimulation intensity and novel stimulation parameters, derive their rationale from studies of brain physiology. These novel parameters simulate normal firing patterns or act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia in motor control. There may also be diagnostic potential of TMS in characterizing individual traits for personalized medicine.

Pain-Related Brain Activity Evoked by Active and Dynamic Arm Movement: Delayed-Onset Muscle Soreness as a Promising Model for Studying Movement-Related Pain in Humans.

ObjectiveTo demonstrate delayed-onset muscle soreness (DOMS) is a suitable model for the study of movement-evoked pain, we attempted to identify brain regions specifically involved in pain evoked by active and dynamic movement under DOMS condition.SubjectTwelve healthy volunteersMethodsDOMS was induced in the left upper-arm flexor muscles by an eccentric elbow contraction exercise. Movement-evoked pain in the affected muscles was evaluated just before (day 0) and after (days 1–7 and 30) the exercise using a visual analog scale. Subjects underwent functional magnetic resonance imaging scans while performing repeated elbow flexion on day 2 (DOMS condition) and day 30 (painless condition). We compared brain activity between the DOMS and painless conditions.ResultsMovement-evoked pain reached peak intensity on day 2 and disappeared by day 30 in all subjects. No subject felt pain at rest on either of these days. Contralateral primary motor cortex (M1), parietal operculum and bilateral presupplementary motor area (pre-SMA) showed greater activity during active and dynamic arm movement with DOMS than during the same movement without pain. There was no difference in activation of brain regions known collectively as the “pain matrix,” except for the parietal operculum, between the two conditions.ConclusionActive and dynamic movement with pain selectively evoked activation of M1, pre-SMA, and parietal operculum, as assessed using DOMS. Our results demonstrate that DOMS is a promising experimental model for the study of movement-evoked pain in humans.

Alteration of Resting-State Brain Sensorimotor Connectivity following Spinal Cord Injury: A Resting-State Functional Magnetic Resonance Imaging Study.

Motor and sensory deficits after spinal cord injury (SCI) result in functional reorganization of the sensorimotor network. While several task-evoked functional magnetic resonance imaging (fMRI) studies demonstrated functional alteration of the sensorimotor network in SCI, there has been no study of the possible alteration of resting-state functional connectivity using resting-state fMRI. The aim of this study was to investigate the changes of brain functional connectivity in the sensorimotor cortex of patients with SCI. We evaluated the functional connectivity scores between brain areas within the sensorimotor network in 18 patients with SCI and 18 controls. Our findings demonstrated that, compared with control subjects, patients with SCI showed increased functional connectivity between primary motor cortex and other motor areas, such as the supplementary motor area and basal ganglia. However, decreased functional connectivity between primary somatosensory cortex and secondary somatosensory cortex also was found in patients with SCI, compared with controls. These findings therefore demonstrated alteration of the resting-state sensorimotor network in patients with SCI, who showed increased connectivity between motor components, and decreased connectivity between sensory components, within the sensorimotor network, suggesting that motor components within the motor network increased in functional connectivity in order to compensate for motor deficits, whereas the sensory network did not show any such increases or compensation for sensory deficits.

Differential modulation of motor network connectivity during movements of the upper and lower limbs

Voluntary movements depend on a well-regulated interplay between the primary motor cortex (M1) and premotor areas. While to date the neural underpinnings of hand movements are relatively well understood, we only have rather limited knowledge on the cortical control of lower-limb movements. Given that our hands and feet have different roles for activities of daily living, with hand movements being more frequently used in a lateralized fashion, we hypothesized that such behavioral differences also impact onto network dynamics underlying upper and lower limb movements. We, therefore, used functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) to investigate differences in effective connectivity underlying isolated movements of the hands or feet in 16 healthy subjects. The connectivity analyses revealed that both movements of the hand and feet were accompanied by strong facilitatory coupling of the respective contralateral M1 representations with premotor areas of both hemispheres. However, excitatory influences were significantly lower for movements of the feet compared to hand movements. During hand movements, the M1hand representation ipsilateral to the movement was strongly inhibited by premotor regions and the contralateral M1 homologue. In contrast, interhemispheric inhibition was absent between the M1foot representations during foot movements. Furthermore, M1foot ipsilateral to the moving foot exerted promoting influences onto contralateral M1foot. In conclusion, the generally stronger and more lateralized coupling pattern associated with hand movements suggests distinct fine-tuning of cortical control to underlie voluntary movements with the upper compared to the lower limb.

Inter-individual variability in cortical excitability and motor network connectivity following multiple blocks of rTMS

The responsiveness to non-invasive neuromodulation protocols shows high inter-individual variability, the reasons of which remain poorly understood. We here tested whether the response to intermittent theta-burst stimulation (iTBS) – an effective repetitive transcranial magnetic stimulation (rTMS) protocol for increasing cortical excitability – depends on network properties of the cortical motor system. We furthermore investigated whether the responsiveness to iTBS is dose-dependent.To this end, we used a sham-stimulation controlled, single-blinded within-subject design testing for the relationship between iTBS aftereffects and (i) motor-evoked potentials (MEPs) as well as (ii) resting-state functional connectivity (rsFC) in 16 healthy subjects. In each session, three blocks of iTBS were applied, separated by 15min.We found that non-responders (subjects not showing an MEP increase of ≥10% after one iTBS block) featured stronger rsFC between the stimulated primary motor cortex (M1) and premotor areas before stimulation compared to responders. However, only the group of responders showed increases in rsFC and MEPs, while most non-responders remained close to baseline levels after all three blocks of iTBS. Importantly, there was still a large amount of variability in both groups.Our data suggest that responsiveness to iTBS at the local level (i.e., M1 excitability) depends upon the pre-interventional network connectivity of the stimulated region. Of note, increasing iTBS dose did not turn non-responders into responders. The finding that higher levels of pre-interventional connectivity precluded a response to iTBS could reflect a ceiling effect underlying non-responsiveness to iTBS at the systems level.

Hand use predicts the structure of representations in sensorimotor cortex.

Fine finger movements are controlled by the population activity of neurons in the hand area of primary motor cortex. Experiments using microstimulation and single-neuron electrophysiology suggest that this area represents coordinated multi-joint, rather than single-finger movements. However, the principle by which these representations are organized remains unclear. We analyzed activity patterns during individuated finger movements using functional magnetic resonance imaging (fMRI). Although the spatial layout of finger-specific activity patterns was variable across participants, the relative similarity between any pair of activity patterns was well preserved. This invariant organization was better explained by the correlation structure of everyday hand movements than by correlated muscle activity. This also generalized to an experiment using complex multi-finger movements. Finally, the organizational structure correlated with patterns of involuntary co-contracted finger movements for high-force presses. Together, our results suggest that hand use shapes the relative arrangement of finger-specific activity patterns in sensory-motor cortex.