Winston Byblow

Threshold tracking primary motor cortex inhibition: the influence of current direction

Publisher: Wiley

Date: 09-2016

DOI: 10.1111/EJN.13369

Abstract: Paired-pulse transcranial magnetic stimulation (TMS) can be used to probe inhibitory activity in primary motor cortex (M1). Recruitment of descending volleys with TMS depends on the induced current direction in M1. Anterior-posterior (AP) stimulation preferentially activates late indirect- (I-) waves that are most susceptible to paired-pulse TMS. Threshold tracking TMS can assess intracortical inhibition however, previous studies have only used a current direction that preferentially recruits early I-waves [posterior-anterior (PA)]. Our objective was to examine intracortical inhibition with threshold tracking TMS designed to preferentially recruit early vs. late I-waves with PA and AP stimulation respectively. Electromyographic recordings were obtained from the right first dorsal interosseous muscle of 15 participants (21-50 years). Motor evoked potentials elicited by TMS over left M1 were recorded for PA, AP and lateromedial (LM) induced currents, with I-wave recruitment calculated as the onset latency difference between PA-LM and AP-LM. Short- and long-interval intracortical inhibition (SICI and LICI) were examined across a range of conditioning stimulus intensities and interstimulus intervals (3 and 100-260 ms) with threshold tracking TMS for PA and AP stimulation. SICI and LICI were greater for AP compared with PA current direction using threshold tracking. In addition, the efficacy of late I-wave recruitment was associated with the extent of SICI for AP but not PA stimulation, and was not associated with LICI. These findings indicate that threshold tracking with an AP-induced current provides a more robust and sensitive measure of M1 intracortical inhibition than PA.

Combining Theta Burst Stimulation With Training After Subcortical Stroke

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 07-2010

DOI: 10.1161/STROKEAHA.110.583278

Abstract: Background and Purpose— Repetitive transcranial magnetic stimulation of the primary motor cortex (M1) may improve outcomes after stroke. The aim of this study was to determine the effects of M1 theta burst stimulation (TBS) and standardized motor training on upper-limb function of patients with chronic stroke. Methods— Ten patients with chronic subcortical stroke and upper-limb impairment were recruited to this double-blind, crossover, sham-controlled study. Intermittent TBS of the ipsilesional M1, continuous TBS of the contralesional M1, and sham TBS were delivered in separate sessions in conjunction with standardized training of a precision grip task using the paretic upper limb. Results— Training after real TBS improved paretic-hand grip-lift kinetics, whereas training after sham TBS resulted in deterioration of grip-lift. Ipsilesional M1 excitability increased after intermittent TBS of the ipsilesional M1 but decreased after continuous TBS of the contralesional M1. Action Research Arm Test scores deteriorated when training followed continuous TBS of the contralesional M1, and this was correlated with reduced ipsilesional corticomotor excitability. Conclusions— Generally, TBS and training led to task-specific improvements in grip-lift. Specifically, continuous TBS of the contralesional M1 led to an overall decrement in upper-limb function, indicating that the contralesional hemisphere may play a pivotal role in recovery after stroke.

Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide

Publisher: Cold Spring Harbor Laboratory

Date: 05-11-2020

DOI: 10.1101/2020.11.04.366856

Abstract: Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Subcortical regions play critical roles in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behavior at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioral data in 828 in iduals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behavior to non-lesioned subcortical volumes (Bonferroni-corrected, p .004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behavior was associated with a smaller ipsilesional thalamic volume in both early (n=179 d =0.68) and subacute (n=274, d =0.46) stroke. In chronic stroke (n=404), worse sensorimotor behavior was associated with smaller ipsilesional putamen ( d =0.52) and nucleus accumbens ( d =0.39) volumes, and a larger ipsilesional lateral ventricle ( d =-0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment n=256) was associated with smaller ipsilesional putamen ( d =0.72) and larger lateral ventricle ( d =-0.41) volumes, while several measures of activity limitations (n=116) showed no significant relationships. In the full cohort across all time (n=828), sensorimotor behavior was associated with the volumes of the ipsilesional nucleus accumbens ( d =0.23), putamen ( d =0.33), thalamus ( d =0.33), and lateral ventricle ( d =-0.23). We demonstrate significant relationships between post-stroke sensorimotor behavior and reduced volumes of subcortical gray matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings may provide additional targets for improving post-stroke sensorimotor outcomes.

Global brain health modulates the impact of lesion damage on post-stroke sensorimotor outcomes

Publisher: Cold Spring Harbor Laboratory

Date: 29-04-2022

DOI: 10.1101/2022.04.27.489791

Abstract: Sensorimotor performance after stroke is strongly related to focal injury measures such as corticospinal tract lesion load. However, the role of global brain health is less clear. Here, we examined the impact of brain age, a measure of neurobiological aging derived from whole brain structural neuroimaging, on sensorimotor outcomes. We hypothesized that stroke lesion damage would result in older brain age, which would in turn be associated with poorer sensorimotor outcomes. We also expected that brain age would mediate the impact of lesion damage on sensorimotor outcomes and that these relationships would be driven by post-stroke secondary atrophy (e.g., strongest in the ipsilesional hemisphere in chronic stroke). We further hypothesized that structural brain resilience, which we define in the context of stroke as the brain’s ability to maintain its global integrity despite focal lesion damage, would differentiate people with better versus worse outcomes. We analyzed cross-sectional high-resolution brain MRI and outcomes data from 963 people with stroke from 38 cohorts worldwide using robust linear mixed-effects regressions to examine the relationship between sensorimotor behavior, lesion damage, and brain age. We used a mediation analysis to examine whether brain age mediates the impact of lesion damage on stroke outcomes and if associations are driven by ipsilesional measures in chronic (≥180 days) stroke. We assessed the impact of brain resilience on sensorimotor outcome using logistic regression with propensity score matching on lesion damage. Stroke lesion damage was associated with older brain age, which in turn was associated with poorer sensorimotor outcomes. Brain age mediated the impact of corticospinal tract lesion load on sensorimotor outcomes most strongly in the ipsilesional hemisphere in chronic stroke. Greater brain resilience, as indexed by younger brain age, explained why people have better versus worse sensorimotor outcomes when lesion damage was fixed. We present novel evidence that global brain health is associated with superior post-stroke sensorimotor outcomes and modifies the impact of focal damage. This relationship appears to be due to post-stroke secondary degeneration. Brain resilience provides insight into why some people have better outcomes after stroke, despite similar amounts of focal injury. Inclusion of imaging-based assessments of global brain health may improve prediction of post-stroke sensorimotor outcomes compared to focal injury measures alone. This investigation is important because it introduces the potential to apply novel therapeutic interventions to prevent or slow brain aging from other fields (e.g., Alzheimer’s disease) to stroke.

Adaptive threshold hunting reveals differences in interhemispheric inhibition between young and older adults

Publisher: Wiley

Date: 28-08-2018

DOI: 10.1111/EJN.14097

Abstract: Interhemispheric inhibition between bilateral motor cortices is important for the performance of unimanual activities and may be compromised with advancing age. Conventionally, interhemispheric inhibition is assessed using paired-pulse transcranial magnetic stimulation (TMS) with constant conditioning and test stimulation parameters. Adaptive threshold hunting TMS, whereby a target motor-evoked potential litude is maintained in the presence of the conditioning, may provide an alternative means of assessment. Furthermore, interhemispheric inhibition may suppress late indirect-waves more so than early indirect-waves which can be preferentially elicited using anterior-posterior (AP) and posterior-anterior (PA) induced currents, respectively. The aim of this study was to assess age-related effects on interhemispheric inhibition using both conventional and threshold hunting techniques with PA- and AP-induced current. In 15 young and 15 older adults, short (10 ms) and long (40 ms) interval interhemispheric inhibition was examined in the nondominant extensor carpi radialis muscle at rest and during voluntary extension of the contralateral wrist. With the conventional technique, there were no age-related differences in short-interval interhemispheric inhibition. With threshold hunting and AP-induced current, young adults exhibited greater short-interval interhemispheric inhibition during contralateral activation compared with rest and compared with older adults. Furthermore, long-interval interhemispheric inhibition was greater in older adults compared with young for both conventional and threshold hunting techniques. Age-related differences in interhemispheric inhibition are evident with threshold hunting using PA- and AP-induced current.

The Yips in Golf

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 11-2006

DOI: 10.1249/01.MSS.0000233792.93540.10

Bilateral Priming Before Wii-based Movement Therapy Enhances Upper Limb Rehabilitation and Its Retention After Stroke

Publisher: SAGE Publications

Date: 13-03-2014

DOI: 10.1177/1545968314523679

Abstract: Background. Motor deficits after a stroke are thought to be compounded by the development of asymmetric interhemispheric inhibition. Bilateral priming was developed to rebalance this asymmetry and thus improve therapy efficacy. Objective. This study investigated the effect of bilateral priming before Wii-based Movement Therapy to improve rehabilitation after stroke. Methods. Ten patients who had suffered a stroke (age, 23-77 years 3-123 months after stroke) underwent a 14-day program of Wii-based Movement Therapy for upper limb rehabilitation. Formal Wii-based Movement Therapy sessions were immediately preceded by 15 minutes of bilateral priming, whereby active flexion-extension of the less affected wrist drove mirror-symmetric passive movements of the more affected wrist through a custom device. Functional movement was assessed at weeks 0 (before therapy), 3 (after therapy), and 28 (follow-up) using the Wolf Motor Function Test (WMFT), upper limb Fugl-Meyer Assessment (FMA), upper limb range of motion, and Motor Activity Log (MAL). Case-matched controls were patients who had suffered a stroke who received Wii-based Movement Therapy but not bilateral priming. Results. Upper limb functional ability improved for both groups on all measures tested. Posttherapy improvement on the FMA for primed patients was twice that of the unprimed patients (37.3% vs 14.6%, respectively) and was significantly better maintained at 28 weeks ( P = .02). Improvements on the WMFT and MAL were similar for both groups, but the pattern of change in range of motion was strikingly different. Conclusions. Bilateral priming before Wii-based Movement Therapy led to a greater magnitude and retention of improvement compared to control, especially measured with the FMA. These data suggest that bilateral priming can enhance the efficacy of Wii-based Movement Therapy, particularly for patients with low motor function after a stroke.

Amplitude of muscle stretch modulates corticomotor gain during passive movement

Publisher: Elsevier BV

Date: 2005

DOI: 10.1016/J.BRAINRES.2004.10.062

Abstract: Previous studies have shown that the excitability of corticomotor projections to forearm muscles exhibit phasic modulation during passive movement (flexion-extension) about the wrist joint. We examined the stimulus-response properties of flexor carpi radialis (FCR) and extensor carpi radialis (ECR) to transcranial magnetic stimulation (TMS) applied over the contralateral motor cortex while the wrist was moved passively at two different sinusoidal frequency- litude relationships. Movement velocity (and therefore, the rate of change in muscle length) at the time of stimulation was held constant. Motor evoked potential (MEP) litudes were facilitated during passive muscle shortening and suppressed during passive muscle lengthening with suppression being more evident at higher stimulation intensities. For both FCR and ECR, during the shortening phase, responses were facilitated during the large litude movement relative to the small litude movement. It is suggested that the altered gain may be related to the thixotropic properties of muscle.

Primary motor cortex disinhibition during motor skill learning

Publisher: American Physiological Society

Date: 07-2014

DOI: 10.1152/JN.00893.2013

Abstract: Motor learning requires practice over a period of time and depends on brain plasticity, yet even for relatively simple movements, there are multiple practice strategies that can be used for skill acquisition. We investigated the role of intracortical inhibition in the primary motor cortex (M1) during motor skill learning. Event-related transcranial magnetic stimulation (TMS) was used to assess corticomotor excitability and inhibition thought to involve synaptic and extrasynaptic γ-aminobutyric acid (GABA). Short intracortical inhibition (SICI) was assessed using 1- and 2.5-ms interstimulus intervals (ISIs). Participants learned a novel, sequential pinch-grip task on a computer in either a repetitive or interleaved practice structure. Both practice structures showed equivalent levels of motor performance at the end of acquisition and at retention 1 wk later. There was a novel task-related modulation of 1-ms SICI. Repetitive practice elicited a greater reduction of 1- and 2.5-ms SICI, i.e., disinhibition, between rest and task acquisition, compared with interleaved practice. These novel findings support the use of a repetitive practice structure for motor learning because the associated effects within M1 have relevance for motor rehabilitation.

A template-based procedure for determining white matter integrity in the internal capsule early after stroke

Publisher: Elsevier BV

Date: 2014

DOI: 10.1016/J.NICL.2013.12.006

Repetitive stimulation of premotor cortex affects primary motor cortex excitability and movement preparation

Publisher: Elsevier BV

Date: 07-2009

DOI: 10.1016/J.BRS.2009.01.001

Abstract: Repetitive transcranial magnetic stimulation can be used to explore functional connectivity between cortical areas. To determine the effects of two theta burst stimulation (TBS) patterns (intermittent, iTBS and continuous, cTBS) of left dorsal premotor cortex (PMd). Left PMd was identified in 11 participants using functional magnetic resonance imaging (fMRI), during performance of complex sequential finger movements. Each participant received iTBS, cTBS, or sham TBS of left PMd in three separate sessions within a randomized, single-blind design. The speed and accuracy of simple and complex sequential reaction time (RT) task performance was measured before and after TBS. The excitability of primary motor cortex (M1) bilaterally, and interhemispheric facilitation from left PMd to right M1, were also measured before and after TBS. iTBS sped up the preparation of complex sequences performed with the right hand, with no detectable changes in M1 excitability. RT performance was maintained after cTBS, in the presence of increased left M1 excitability and suppressed right M1 excitability. Facilitatory and inhibitory TBS protocols applied to left PMd differentially alter corticomotor excitability and behavior, which suggests that these protocols affect different neuronal populations.

A global pause generates nonselective response inhibition during selective stopping

Publisher: Cold Spring Harbor Laboratory

Date: 03-03-2023

DOI: 10.1101/2023.03.02.530898

Abstract: 1 Response inhibition is essential for terminating inappropriate actions. Selective response inhibition may be required when stopping part of a multicomponent action. However, a persistent response delay ( stopping-interference effect ) indicates nonselective response inhibition during selective stopping. This study aimed to elucidate whether nonselective response inhibition is the consequence of a global pause process during attentional capture or specific to a nonselective cancel process during selective stopping. We hypothesised that the stopping-interference effect would be larger in response to stop than ignore signals, owing to stronger nonselective response inhibition for explicit selective stopping. Twenty healthy human participants of either sex performed a bimanual anticipatory response inhibition paradigm with selective stop and ignore signals. Frontocentral and sensorimotor beta (β)-bursts were recorded with electroencephalography. Corticomotor excitability (CME) and short-interval intracortical inhibition (SICI) in primary motor cortex were recorded with transcranial magnetic stimulation. Behaviourally, responses in the non-signalled hand were delayed during selective ignore and stop trials. The response delay was largest during selective stop trials and indicated that the stopping-interference effect could not be attributed entirely to attentional capture. A stimulus-nonselective increase in frontocentral β-bursts occurred during stop and ignore trials, whilst sensorimotor response inhibition was reflected in maintenance of β-bursts and SICI relative to disinhibition observed during go trials. Signatures of response inhibition in the sensorimotor cortex contralateral to the responding hand were not associated with the magnitude of stopping-interference. Therefore, nonselective response inhibition during selective stopping results primarily from a nonselective pause process but does not entirely account for the stopping-interference effect. 2 Selective stopping is a complex form of response inhibition where a person must execute and cancel part of an action at the same time. A stopping-interference effect exemplifies the complexity of selective stopping. The present study examined whether nonselective response inhibition during selective stopping results from a global pause during attentional capture or is specific to a deliberate cancel process. Behaviourally, the interference effect was larger during selective stop stimuli than selective ignore stimuli. However, neurophysiological signatures of nonselective response inhibition were elicited in response to both stop and ignore stimuli. These findings indicate that nonselective response inhibition during selective stopping results primarily from a nonselective pause process but does not entirely account for the stopping-interference effect.

Cathodal transcranial direct current stimulation of the primary motor cortex improves selective muscle activation in the ipsilateral arm.

Publisher: American Physiological Society

Date: 06-2011

DOI: 10.1152/JN.00171.2011

Abstract: Proximal upper limb muscles are represented bilaterally in primary motor cortex. Goal-directed upper limb movement requires precise control of proximal and distal agonist and antagonist muscles. Failure to suppress antagonist muscles can lead to abnormal movement patterns, such as those commonly experienced in the proximal upper limb after stroke. We examined whether noninvasive brain stimulation of primary motor cortex could be used to improve selective control of the ipsilateral proximal upper limb. Thirteen healthy participants performed isometric left elbow flexion by contracting biceps brachii (BB agonist) and left forearm pronation (BB antagonist) before and after 20 min of cathodal transcranial direct current stimulation (c-tDCS) or sham tDCS of left M1. During the tasks, motor evoked potentials (MEPs) in left BB were acquired using single-pulse transcranial magnetic stimulation of right M1 150–270 ms before muscle contraction. As expected, left BB MEPs were facilitated before flexion and suppressed before pronation. After c-tDCS, left BB MEP litudes were reduced compared with sham stimulation, before pronation but not flexion, indicating that c-tDCS enhanced selective muscle activation of the ipsilateral BB in a task-specific manner. The potential for c-tDCS to improve BB antagonist control correlated with BB MEP litude for pronation relative to flexion, expressed as a selectivity ratio. This is the first demonstration that selective muscle activation in the proximal upper limb can be improved after c-tDCS of ipsilateral M1 and that the benefits of c-tDCS for selective muscle activation may be most effective in cases where activation strategies are already suboptimal. These findings may have relevance for the use of tDCS in rehabilitation after stroke.

Intracortical Inhibition During Volitional Inhibition of Prepared Action

Publisher: American Physiological Society

Date: 06-2006

DOI: 10.1152/JN.01334.2005

Abstract: Volitional inhibition is the voluntary prevention of a prepared movement. Here we ask whether primary motor cortex (M1) is a site of convergence of cortical activity associated with movement preparation and volitional inhibition. Volitional inhibition was studied by presenting a stop signal before execution of an anticipated response that requires a key lift to intercept a revolving dial. Motor evoked potentials (MEPs) were elicited in intrinsic hand muscles by transcranial magnetic stimulation (TMS) to assess corticomotor excitability and short interval intracortical inhibition (sICI) during task performance. The closer the stop cue was presented to the anticipated response, the harder it was for subjects to inhibit their response. Corticomotor pathway excitability was temporally modulated during volitional inhibition. Using subthreshold TMS, corticomotor excitability was reduced for Stop trials relative to Go trials from 140 ms after the cue. sICI was significantly greater for Stop trials compared with Go trials at a time that preceded the onset of muscle activity associated with the anticipated response. These results provide evidence that volitional inhibition is exerted at a cortical level and that inhibitory networks within M1 contribute to volitional inhibition of prepared action.

Priming the motor system enhances the effects of upper limb therapy in chronic stroke

Publisher: Oxford University Press (OUP)

Date: 20-03-2008

DOI: 10.1093/BRAIN/AWN051

Abstract: After stroke, the function of primary motor cortex (M1) between the hemispheres may become unbalanced. Techniques that promote a re-balancing of M1 excitability may prime the brain to be more responsive to rehabilitation therapies and lead to improved functional outcomes. The present study examined the effects of Active-Passive Bilateral Therapy (APBT), a putative movement-based priming strategy designed to reduce intracortical inhibition and increase excitability within the ipsilesional M1. Thirty-two patients with upper limb weakness at least 6 months after stroke were randomized to a 1-month intervention of self-directed motor practice with their affected upper limb (control group) or to APBT for 10-15 min prior to the same motor practice (APBT group). A blinded clinical rater assessed upper limb function at baseline, and immediately and 1 month after the intervention. Transcranial magnetic stimulation was used to assess M1 excitability. Immediately after the intervention, motor function of the affected upper limb improved in both groups (P < 0.005). One month after the intervention, the APBT group had better upper limb motor function than control patients (P < 0.05). The APBT group had increased ipsilesional M1 excitability (P < 0.025), increased transcallosal inhibition from ipsilesional to contralesional M1 (P < 0.01) and increased intracortical inhibition within contralesional M1 (P < 0.005). None of these changes were found in the control group. APBT produced sustained improvements in upper limb motor function in chronic stroke patients and induced specific and sustained changes in motor cortex inhibitory function. We speculate that APBT may have facilitated plastic reorganization in the brain in response to motor therapy. The utility of APBT as an adjuvant to physical therapy warrants further consideration.

The PREP algorithm predicts potential for upper limb recovery after stroke

Publisher: Oxford University Press (OUP)

Date: 10-06-2012

DOI: 10.1093/BRAIN/AWS146

Abstract: Stroke is a leading cause of adult disability and the recovery of motor function is important for independence in activities of daily living. Predicting motor recovery after stroke in in idual patients is difficult. Accurate prognosis would enable realistic rehabilitation goal-setting and more efficient allocation of resources. The aim of this study was to test and refine an algorithm for predicting the potential for recovery of upper limb function after stroke. Forty participants were prospectively enrolled within 3 days of ischaemic stroke. First, shoulder abduction and finger extension strength were graded 72 h after stroke onset to compute a shoulder abduction and finger extension score. Secondly, transcranial magnetic stimulation was used to assess the functional integrity of descending motor pathways to the affected upper limb. Third, diffusion-weighted magnetic resonance imaging was used to assess the structural integrity of the posterior limbs of the internal capsules. Finally, these measures were combined in the PREP algorithm for predicting an in idual's potential for upper limb recovery at 12 weeks, measured with the Action Research Arm Test. A cluster analysis was used to independently group patients according to Action Research Arm Test score at 12 weeks, for comparison with predictions from the PREP algorithm. There was excellent correspondence between the cluster analysis of Action Research Arm Test score at 12 weeks and predictions made with the PREP algorithm. The algorithm had positive predictive power of 88%, negative predictive power of 83%, specificity of 88% and sensitivity of 73%. This study provides preliminary data in support of the PREP algorithm for the prognosis of upper limb recovery in in idual patients. PREP may enable tailored planning of rehabilitation and more accurate stratification of patients in clinical trials.

Ipsilateral Motor Pathways after Stroke: Implications for Non-Invasive Brain Stimulation

Publisher: Frontiers Media SA

Date: 2013

DOI: 10.3389/FNHUM.2013.00184

Stop and Go: The Neural Basis of Selective Movement Prevention

Publisher: MIT Press - Journals

Date: 06-2009

DOI: 10.1162/JOCN.2009.21081

Abstract: Converging lines of evidence show that volitional movement prevention depends on the right prefrontal cortex (PFC), especially the right inferior frontal gyrus (IFG). Selective movement prevention refers to the rapid prevention of some, but not all, movement. It is unknown whether the IFG, or other prefrontal areas, are engaged when movement must be selectively prevented, and whether additional cortical areas are recruited. We used rapid event-related fMRI to investigate selective and nonselective movement prevention during performance of a temporally demanding anticipatory task. Most trials involved simultaneous index and middle finger extension. Randomly interspersed trials required the prevention of one, or both, finger movements. Regions of the right hemisphere, including the IFG, were active for selective and nonselective movement prevention, with an overlap in the inferior parietal cortex and the middle frontal gyrus. Selective movement prevention caused a significant delay in movement initiation of the other digit. These trials were associated with activation of the medial frontal cortex. The results provide support for a right-hemisphere network that temporarily “brakes” all movement preparation. When movement is selectively prevented, the supplementary motor cortex (SMA re-SMA) may participate in conflict resolution and subsequent reshaping of excitatory drive to the motor cortex.

Cutaneous anesthesia of the forearm enhances sensorimotor function of the hand

Publisher: American Physiological Society

Date: 15-02-2013

DOI: 10.1152/JN.00813.2012

Abstract: Temporary deafferentation of the upper limb, with ischemic or anesthetic nerve block, has rapid effects on sensorimotor cortex. Cutaneous anesthesia of the forearm has recently been found to improve sensory and motor function of the paretic hand in chronic stroke patients. However, the neurophysiological mechanisms are unknown. The aim of this study was to investigate the behavioral and neurophysiological effects of cutaneous forearm anesthesia. Twenty-five healthy right-handed adults participated in this double-blind, randomized study. Participants completed two sessions, with either a topical anesthesia cream (EMLA) or placebo applied to their left forearm in each session. Thresholds for cutaneous sensation and spatial acuity of the left hand were measured before and after the intervention. Transcranial magnetic stimulation was used to measure corticomotor excitability and short-interval intracortical inhibition in the left first dorsal interosseous and abductor digiti minimi muscles before and after the intervention. Manual dexterity was assessed with the grooved pegboard task after the intervention in each session. Left-hand dexterity improved to a greater extent after treatment with EMLA than placebo, and this was related to improved spatial acuity at the fingertips. Corticomotor excitability remained stable, and short-interval intracortical inhibition increased after EMLA treatment. We have confirmed and extended previous reports that cutaneous forearm anesthesia results in improved spatial acuity and manual dexterity of the ipsilateral hand. The neurophysiological mechanisms involve an increase in intracortical inhibition, which may improve the precision of voluntary movement. These results lend support to the therapeutic application of EMLA in movement rehabilitation.

‘I-wave’ Recruitment Determines Response to tDCS in the Upper Limb, but Only So Far

Publisher: Elsevier BV

Date: 11-2015

DOI: 10.1016/J.BRS.2015.07.027

Abstract: Anodal transcranial direct current stimulation (a-tDCS) can facilitate primary motor cortex (M1), but the modulation of motor evoked potentials (MEPs) by a-tDCS varies between participants, and may depend on the balance between early versus late I-wave recruitment, as assessed by the difference in MEP latency between latero-medial and anterior-posterior cortical currents induced by transcranial magnetic stimulation (TMS). To date, the dependence of tDCS after-effects on I-wave recruitment has only been investigated in intrinsic hand muscles. In order to better understand the effects of tDCS across the upper limb, the present study examined I-wave recruitment and MEP modulation by a-tDCS or dual-hemisphere tDCS in muscles of the forearm (Extensor Carpi Radialis ECR) and proximal upper limb (Biceps Brachii BB). We conducted a randomized double-blind study with 18 healthy adults. Each received anodal, dual-hemisphere, or sham tDCS over M1 in separate sessions (tDCS, 1 mA for 15 min). Linear regression analyzes showed a-tDCS modulated MEP size dependent on the latency difference in the ECR (P = 0.01) but not BB (P = 0.28). In iduals with small MEP latency differences showed the expected facilitation of ECR MEPs after a-tDCS, whereas those with large MEP latency differences had suppressed ECR MEPs after a-tDCS. This relationship was not present after dual-hemisphere or sham tDCS in either muscle (all P > 0.32). I-wave recruitment can predict the after-effects of a-tDCS in the distal but not proximal upper limb. These findings provide further insight into the variability of tDCS after-effects, and the relationship between I-wave recruitment and putative mechanisms of tDCS.

Conventional or threshold-hunting TMS? A tale of two SICIs

Publisher: Elsevier BV

Date: 11-2018

DOI: 10.1016/J.BRS.2018.07.047

Abstract: In human primary motor cortex (M1), the paired-pulse transcranial magnetic stimulation (TMS) paradigm of short-interval intracortical inhibition (SICI) can be expressed conventionally as a percent change in the relative litude of a conditioned motor evoked potential to non-conditioned or adaptive threshold-hunting a target motor evoked potential litude in the absence or presence of a conditioning stimulus, and noting the relative change in stimulation intensity. The suitability of each approach may depend on the induced current direction, which probe separate M1 interneuronal populations. To examine the influence of conditioning stimulus intensity, interstimulus interval (ISI) and current direction for adaptive threshold-hunting and conventional SICI using equivalent TMS intensities. In 16 participants (21-32 years), SICI was examined using adaptive threshold-hunting and conventional paired-pulse TMS with posterior-anterior and anterior-posterior stimulation, ISIs of 2 and 3 ms, and a range of conditioning intensities. Inhibition with adaptive threshold-hunting was greater for anterior-posterior stimulation with an ISI of 3 ms (23.6 ± 9.0%) compared with 2 ms (7.5 ± 7.8%, P < 0.001) and posterior-anterior stimulation at both ISIs (2 ms 8.6 ± 8.7%, 3 ms 5.9 ± 4.8% P < 0.001). There was an association between inhibition obtained with conventional and adaptive threshold-hunting for posterior-anterior but not anterior-posterior stimulation (2 ms only, r = 0.68, P = 0.03). More inhibition was evident with anterior-posterior than posterior-anterior current for both adaptive threshold-hunting and conventional paired-pulse TMS. Assessment of SICI with anterior-posterior stimulation was not directly comparable between the two approaches. However, the amount of inhibition was dependent on conditioning stimulus intensity and ISI for both SICI techniques.

Are ipsilateral motor evoked potentials subject to intracortical inhibition?

Publisher: American Physiological Society

Date: 03-2016

DOI: 10.1152/JN.01139.2015

Abstract: Paired-pulse transcranial magnetic stimulation (TMS) can be used to examine intracortical inhibition in primary motor cortex (M1), termed short-interval intracortical inhibition (SICI). To our knowledge, SICI has only been demonstrated in contralateral motor evoked potentials (MEPs). Ipsilateral MEPs (iMEPs) are assumed to reflect excitability of an uncrossed oligosynaptic pathway, and can sometimes be evoked in proximal upper-limb muscles using high-intensity TMS. We examined whether iMEPs in the biceps brachii (BB) would be suppressed by subthreshold conditioning, therefore demonstrating SICI of iMEPs. TMS was delivered to the dominant M1 to evoke conditioned (C) and nonconditioned (NC) iMEPs in the nondominant BB of healthy participants during weak bilateral elbow flexion. The conditioning stimulus intensities tested were 85%, 100%, and 115% of active motor threshold (AMT), at 2 ms and 4 ms interstimulus intervals (ISI). The iMEP ratio (C/NC) was calculated for each condition to assess the amount of inhibition. Inhibition of iMEPs was present at 2 ms ISI with 100% and 115% AMT (both P 0.03), mediated by a reduction in persistence and size (all P 0.05). To our knowledge, this is the first demonstration of SICI of iMEPs. This technique may be useful as a tool to better understand the role of ipsilateral M1 during functional motor tasks.

Neurophysiological and behavioural effects of dual-hemisphere transcranial direct current stimulation on the proximal upper limb

Publisher: Springer Science and Business Media LLC

Date: 09-01-2016

DOI: 10.1007/S00221-015-4547-7

Abstract: Dual-hemisphere transcranial direct current stimulation over the primary motor cortex (M1-M1 tDCS) is assumed to modulate neural excitability in a polarity-dependent manner and improve motor performance of the hand. In the proximal upper limb, the neurophysiological and behavioural after-effects of M1-M1 tDCS are not well known. This study investigated the after-effects of M1-M1 tDCS on contralateral, ipsilateral and transcallosal excitability to the proximal upper limb muscle biceps brachii (BB). Circle tracing was used to assess motor performance before and after tDCS as this task requires coordination of proximal and distal musculature. Sixteen healthy right-handed adults participated in the study, each receiving M1-M1 tDCS (1 mA, 15 min) or sham tDCS in separate sessions. The anode was positioned over right M1 and cathode over left M1. M1-M1 tDCS suppressed transcallosal inhibition from the M1 under the cathode (P 0.6). The study provides important information regarding inconsistent neurophysiological and behavioural changes following tDCS that have implications for future tDCS research on the motor system.

Proactive interhemispheric disinhibition supports response preparation during selective stopping

Publisher: Cold Spring Harbor Laboratory

Date: 10-09-2022

DOI: 10.1101/2022.09.08.507205

Abstract: Response inhibition is essential for terminating inappropriate actions. A substantial delay may occur in the response of the non-stopped effector when only part of a multi-effector action is terminated. This stopping-interference effect has been attributed to nonselective response inhibition processes and can be reduced with proactive cueing. This study aimed to elucidate the role of interhemispheric primary motor cortex (M1-M1) influences during selective stopping with proactive cueing. We hypothesized that stopping-interference would be reduced as stopping certainty increased, owing to proactive recruitment of interhemispheric facilitation or interhemispheric inhibition when cued to respond or stop, respectively. Twenty-three healthy human participants performed a bimanual anticipatory response inhibition paradigm with cues signaling the likelihood of a stop-signal occurring. Dual-coil transcranial magnetic stimulation was used to determine corticomotor excitability (CME), interhemispheric inhibition (IHI), and interhemispheric facilitation (IHF) in the left hand at rest and during response preparation. Response times slowed and stopping-interference decreased with cues signaling increased stopping certainty. Proactive response inhibition was marked by a reduced rate of rise and faster cancel time in electromyographical bursts during stopping. There was a nonselective release of IHI but not CME from rest to in-task response preparation, while IHF was not observed in either context. An effector-specific CME but not IHF or IHI reduction was observed when the left hand was cued to stop. These findings indicate that the stopping-interference effect can be reduced through proactive suppression. Interhemispheric M1-M1 channels modulate inhibitory tone that supports responding, but not selective stopping, in a proactive response inhibition context. Response inhibition is essential for terminating inappropriate actions and, in some cases, may be required for only part of a multi-effector action. The present study examined interhemispheric influences between the primary motor cortices during selective stopping with proactive cueing. Stopping selectivity was greater with increased stopping certainty and marked by proactive response inhibition of the hand cued to stop. Inhibitory interhemispheric influences were released during response preparation but were not affected by proactive cueing. These findings indicate that between-hand stopping can be selective with proactive cueing, but cue-related improvements are unlikely to reflect advance engagement of interhemispheric influences between primary motor cortices.

Mirror Symmetric Bimanual Movement Priming Can Increase Corticomotor Excitability and Enhance Motor Learning

Publisher: Public Library of Science (PLoS)

Date: 22-03-2012

DOI: 10.1371/JOURNAL.PONE.0033882

Lateralization of motor imagery following stroke

Publisher: Elsevier BV

Date: 08-2007

DOI: 10.1016/J.CLINPH.2007.05.008

Abstract: Motor imagery may activate the primary motor cortex (M1) and promote functional recovery following stroke. We investigated whether the hemisphere affected by stroke affects performance and M1 activity during motor imagery. Twelve stroke patients (6 left, 6 right hemisphere) and eight healthy age-matched adults participated. Experiment 1 assessed the speed and ease of actual and imagined motor performance. Experiment 2 measured corticomotor excitability during imagined movement of each hand separately, and both hands together, using transcranial magnetic stimulation. For control participants, imagined movements were performed more slowly than actual movements, and right-hand MEPs were facilitated when they imagined moving their right hand or both hands together. Patients reported being able to imagine movements with either hand, despite no measurable facilitation of MEPs in the stroke-affected hand. In left hemisphere patients, MEPs were facilitated in the left hand during imagery of the right hand and both hands together. In right hemisphere patients, motor imagery did not facilitate MEPs in either hand. Motor imagery does not appear to facilitate the ipsilesional M1 following stroke. Motor imagery may play a role in rehabilitating movement planning, but its role in directly facilitating corticomotor output appears limited.

A dissociation between propriospinal facilitation and inhibition after bilateral transcranial direct current stimulation

Publisher: American Physiological Society

Date: 06-2014

DOI: 10.1152/JN.00879.2013

Abstract: Propriospinal premotoneurons (PN) are essential for accurate control of the upper limb. They receive bilateral input from premotor (PM) and primary motor (M1) cortices. In humans, excitability of PNs can be estimated from motor-evoked potentials (MEPs) by pairing a descending volley using transcranial magnetic stimulation (TMS) to summate with an ascending volley from peripheral nerve stimulation at the C 3 –C 4 level of the spinal cord. Transcranial direct current stimulation (tDCS) alters excitability of cortical and subcortical areas. A recent study demonstrated that cathodal tDCS can suppress facilitatory (FAC) and inhibitory (INH) components of PN excitability, presumably via effects on corticoreticulospinal neurons (Bradnam LV, Stinear CM, Lewis GN, Byblow WD. J Neurophysiol 103: 2382–2389, 2010). The present study investigated the effects of bilateral tDCS with healthy subjects. The cathode was placed over left dorsal PM or M1 and the anode over right M1 in separate sessions (PM-M1, M1-M1, or Sham). TMS of right M1 elicited MEPs in left biceps brachii across a range of TMS intensities chosen to examine PN-mediated FAC and INH. Conditioning was applied using median nerve stimulation with an interstimulus interval that coincided with TMS and peripheral volleys summating at the C 3 –C 4 level. All participants showed FAC at TMS intensities near active motor threshold and INH at slightly higher intensities. After tDCS, FAC was reduced for M1-M1 compared with Sham but not after PM-M1 stimulation. Contrary to an earlier study with cathodal tDCS, INH was unchanged across all sessions. The difference between these and earlier findings may relate to dual- vs. single-hemisphere M1 stimulation. M1-M1 tDCS may be a useful adjuvant to techniques that aim to reduce upper limb impairment after stroke.

Primary motor cortex and movement prevention: Where Stop meets Go

Publisher: Elsevier BV

Date: 05-2009

DOI: 10.1016/J.NEUBIOREV.2008.08.013

Abstract: Processes that engage frontal cortex and the basal ganglia are responsible for the prevention of planned movements. Here, we review the role of primary motor cortex (M1) in this function. M1 receives and integrates input from a range of cortical and subcortical sites. It is also the final cortical processing site for voluntary motor commands, before they descend to the spinal cord. Inhibitory networks within M1 may be an important mechanism for the prevention or suppression of movement. Transcranial magnetic stimulation (TMS) has been used to evaluate corticospinal excitability and intracortical inhibition in humans, during the performance of a range of movement selection and prevention tasks. This review explores how M1 intracortical inhibition is selectively reduced to initiate desired voluntary movements, while movement prevention is associated with rapid, non-selective recruitment of inhibition within M1. The relationship between deficient intracortical inhibition and behavioural inhibition is also explored. Ex les of neuropathology are reviewed, including focal dystonia, attention deficit hyperactivity disorder and Tourette syndrome. The strengths and limitations of TMS in the study of movement prevention are also discussed. While the precise functional links between M1 neuronal populations and the fronto-basal-ganglia network activated by movement prevention have yet to be elucidated, it is clear that M1 plays a critical role in the final processing stage of response inhibition.

Priming sensorimotor cortex to enhance task-specific training after subcortical stroke

Publisher: Elsevier BV

Date: 07-2014

DOI: 10.1016/J.CLINPH.2013.11.020

Abstract: This double-blind sham-controlled crossover study investigated the interactions between primary sensory and motor cortex after stroke and their response to Theta Burst Stimulation (TBS). Thirteen chronic subcortical stroke patients with upper limb impairment performed standardised dexterity training primed with ipsilesional M1 intermittent TBS (iTBSiM1), contralesional M1 continuous TBS (cTBScM1) or sham TBS. The effects on sensorimotor integration, corticomotor excitability, sensation and grip-lift kinetics were examined. After iTBSiM1, improvements in paretic grip-lift performance were accompanied by an immediate facilitation of ipsilesional M1 excitability and a subsequent increase in ipsilesional short latency afferent inhibition (SAI) during training. Precision grip-lift performance improved after cTBScM1 and training, alongside increased ipsilesional M1 excitability with no effect on ipsilesional SAI. There were no effects on sensory performance. Primary motor cortex iTBS not only modulates M1 corticospinal excitability but also increases M1 receptiveness to sensory input. Priming with iTBSiM1 may enhance ipsilesional sensorimotor integration and facilitate better quality sensorimotor training after subcortical stroke.

Theta Burst Stimulation of Human Primary Motor Cortex Degrades Selective Muscle Activation in the Ipsilateral Arm

Publisher: American Physiological Society

Date: 11-2010

DOI: 10.1152/JN.00365.2010

Abstract: This study investigated whether repetitive transcranial magnetic stimulation (TMS) delivered as continuous theta burst stimulation (cTBS) to left M1 degraded selective muscle activation in the contralateral and ipsilateral upper limb in healthy participants. Contralateral motor-evoked potentials (cMEPs) were elicited in left and right biceps brachii (BB) before either elbow flexion or forearm pronation. A neurophysiological index, the excitability ratio (ER), was computed from the relative size of BB cMEPs before each type of movement. Short interval intracortical inhibition (SICI) was assessed in cMEPs of right BB with paired-pulse TMS of left M1. Ipsilateral MEPs (iMEPs) and silent periods (iSPs) were measured in left BB with single-pulse TMS of left M1. Low-intensity cTBS was expected to suppress corticospinal output from left M1. A sham condition was also included. Real but not sham cTBS caused increases in BB ER bilaterally. In the right arm, ER increased because BB cMEPs before flexion were less facilitated, whereas cMEPs in the pronation task were unaffected. This was accompanied by an increase in left M1 SICI. In the left arm, ER increased because BB cMEPs before pronation were facilitated but were unaffected in the flexion task. There was also facilitation of left BB iMEPs. These changes in the left arm are consistent with inappropriate facilitation of left BB α-motoneurons (αMNs) before pronation. This is the first demonstration that cTBS of M1 can alter excitability of neurons controlling ipsilateral proximal musculature and degrade ipsilateral upper limb motor control, providing evidence that ipsilateral and contralateral M1 shape the spatial and temporal characteristics of proximal muscle activation appropriate for the task at hand.

Task-Dependent Modulation of Propriospinal Inputs to Human Shoulder

Publisher: American Physiological Society

Date: 10-2008

DOI: 10.1152/JN.90786.2008

Abstract: In the human upper limb a proportion of the descending corticospinal command may be relayed through cervical propriospinal premotoneurons. This may serve to coordinate movements involving multiple joints of the arm, such as reaching. The present study was conducted to determine whether a shoulder stabilizing muscle, infraspinatus (INF), is functionally integrated into the putative cervical propriospinal network, and whether there is task-dependent modulation of the network. Fourteen healthy adults participated in this study. Responses in the right INF were evoked by transcranial magnetic stimulation over the motor cortex and compared with responses conditioned by ulnar nerve stimulation. Interstimulus intervals were chosen to summate inputs at the level of the premotoneurons. Participants performed a forearm and shoulder muscle cocontraction task or a grip-lift task that also coactivated forearm and shoulder muscles. During the cocontraction task, INF motor-evoked potentials were significantly facilitated by ulnar nerve stimulation at low intensities and suppressed at higher intensities. Only facilitation reached significance during the grip-lift task. We have shown for the first time that propriospinal pathways may connect the hand to the rotator cuff of the shoulder. The modulation of facilitation/suppression during the grip-lift task suggests that inhibition of propriospinal premotoneurons is down-regulated in a task-dependent manner to increase the gain in the feedback reflex loop from forearm and hand muscles as required.

Primed Physical Therapy Enhances Recovery of Upper Limb Function in Chronic Stroke Patients

Publisher: SAGE Publications

Date: 15-07-2000

DOI: 10.1177/1545968315595285

Abstract: Background. Recovery of upper limb function is important for regaining independence after stroke. Objective. To test the effects of priming upper limb physical therapy with intermittent theta burst stimulation (iTBS), a form of noninvasive brain stimulation. Methods. Eighteen adults with first-ever chronic monohemispheric subcortical stroke participated in this randomized, controlled, triple-blinded trial. Intervention consisted of priming with real or sham iTBS to the ipsilesional primary motor cortex immediately before 45 minutes of upper limb physical therapy, daily for 10 days. Changes in upper limb function (Action Research Arm Test [ARAT]), upper limb impairment (Fugl-Meyer Scale), and corticomotor excitability, were assessed before, during, and immediately, 1 month and 3 months after the intervention. Functional magnetic resonance images were acquired before and at one month after the intervention. Results. Improvements in ARAT were observed after the intervention period when therapy was primed with real iTBS, but not sham, and were maintained at 1 month. These improvements were not apparent halfway through the intervention, indicating a dose effect. Improvements in ARAT at 1 month were related to balancing of corticomotor excitability and an increase in ipsilesional premotor cortex activation during paretic hand grip. Conclusions. Two weeks of iTBS-primed therapy improves upper limb function at the chronic stage of stroke, for at least 1 month postintervention, whereas therapy alone may not be sufficient to alter function. This indicates a potential role for iTBS as an adjuvant to therapy delivered at the chronic stage.

Somatosensory and transcranial direct current stimulation effects on manual dexterity and motor cortex function: A metaplasticity study

Publisher: Elsevier BV

Date: 07-2019

DOI: 10.1016/J.BRS.2019.02.010

Abstract: Non-invasive neuromodulation may provide treatment strategies for neurological deficits affecting movement, such as stroke. For ex le, weak electrical stimulation applied to the hand by wearing a "mesh glove" (MGS) can transiently increase primary motor cortex (M1) excitability. Conversely, transcranial direct current stimulation with the cathode over M1 (c-tDCS) can decrease corticomotor excitability. We applied M1 c-tDCS as a priming adjuvant to MGS and hypothesised metaplastic effects would be apparent in improved motor performance and modulation of M1 inhibitory and facilitatory circuits. Sixteen right-handed neurologically healthy in iduals participated in a repeated measures cross-over study nine minutes of sham- or c-tDCS followed by 30 min of suprasensory threshold MGS. Dexterity of the non-dominant (left) hand was assessed using the grooved pegboard task, and measures of corticomotor excitability, intracortical facilitation, short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI), and SAI in the presence of SICI (SAIxSICI), were obtained at baseline, post-tDCS, and 0, 30 and 60 min post-MGS. There was a greater improvement in grooved pegboard completion times with c-tDCS primed MGS than sham + MGS. There was also more pronounced disinhibition of SAI. However, disinhibition of SAI in the presence of SICI was less and rest motor threshold higher compared to sham + MGS. The results indicate a metaplastic modulation of corticomotor excitability with c-tDCS primed MGS. Further studies are warranted to determine how various stimulation approaches can induce metaplastic effects on M1 neuronal circuits to boost functional gains obtained with motor practice.

Functional Connectivity Between Secondary and Primary Motor Areas Underlying Hand–Foot Coordination

Publisher: American Physiological Society

Date: 07-2007

DOI: 10.1152/JN.00325.2007

Abstract: Coincident hand and foot movements are more reliably performed in the same direction than in opposite directions. Using transcranial magnetic stimulation (TMS) to assess motor cortex function, we examined the physiological basis of these movements across three novel experiments. Experiment 1 demonstrated that upper limb corticomotor excitability changed in a way that facilitated isodirectional movements of the hand and foot, during phasic and isometric muscle activation conditions. Experiment 2 demonstrated that motor cortex inhibition was modified with active, but not passive, foot movement in a manner that facilitated hand movement in the direction of foot movement. Together, these findings demonstrate that the coupling between motor representations within motor cortex is activity dependent. Because there are no known connections between hand and foot areas within primary motor cortex, experiment 3 used a dual-coil paired-pulse TMS protocol to examine functional connectivity between secondary and primary motor areas during active ankle dorsiflexion and plantarflexion. Dorsal premotor cortex (PMd) and supplementary motor area (SMA) conditioning, but not ventral premotor cortex (PMv) conditioning, produced distinct phases of task-dependent modulation of excitability of forearm representations within primary motor cortex (M1). Networks involving PMd–M1 facilitate isodirectional movements of hand and foot, whereas networks involving SMA–M1 facilitate corticomotor pathways nonspecifically, which may help to stabilize posture during interlimb coordination. These results may have implications for targeted neurorehabilitation after stroke.

Acute aerobic exercise modulates primary motor cortex inhibition

Publisher: Springer Science and Business Media LLC

Date: 02-09-2016

DOI: 10.1007/S00221-016-4767-5

Abstract: Aerobic exercise can enhance neuroplasticity although presently the neural mechanisms underpinning these benefits remain unclear. One possible mechanism is through effects on primary motor cortex (M1) function via down-regulation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The aim of the present study was to examine how corticomotor excitability (CME) and M1 intracortical inhibition are modulated in response to a single bout of moderate intensity aerobic exercise. Ten healthy right-handed adults were participants. Single- and paired-pulse transcranial magnetic stimulation was applied over left M1 to obtain motor-evoked potentials in the right flexor pollicis brevis. We examined CME, cortical silent period (SP) duration, short- and long-interval intracortical inhibition (SICI, LICI), and late cortical disinhibition (LCD), before and after acute aerobic exercise (exercise session) or an equivalent duration without exercise (control session). Aerobic exercise was performed on a cycle ergometer for 30 min at a workload equivalent to 60 % of maximal cardiorespiratory fitness (VO

Can motor imagery and hypnotic susceptibility explain Conversion Disorder with motor symptoms?

Publisher: Elsevier BV

Date: 08-2016

DOI: 10.1016/J.NEUROPSYCHOLOGIA.2016.06.030

Abstract: Marked distortions in sense of agency can be induced by hypnosis in susceptible in iduals, including alterations in subjective awareness of movement initiation and control. These distortions, with associated disability, are similar to those experienced with Conversion Disorder (CD), an observation that has led to the hypothesis that hypnosis and CD share causal mechanisms. The purpose of this review is to explore the relationships among motor imagery (MI), hypnotic susceptibility, and CD, then to propose how MI ability may contribute to hypnotic responding and CD. Studies employing subjective assessments of mental imagery have found little association between imagery abilities and hypnotic susceptibility. A positive association between imagery abilities and hypnotic susceptibility becomes apparent when objective measures of imagery ability are employed. A candidate mechanism to explain motor responses during hypnosis is kinaesthetic MI, which engages a strategy that involves proprioception or the "feel" of movement when no movement occurs. Motor suppression imagery (MSI), a strategy involving inhibition of movement, may provide an alternate objective measurable phenomenon that underlies both hypnotic susceptibility and CD. Evidence to date supports the idea that there may be a positive association between kinaesthetic MI ability and hypnotic susceptibility. Additional evidence supports a positive association between hypnotic susceptibility and CD. Disturbances in kinaesthetic MI performance in CD patients indicate that MI mechanisms may also underlie CD symptoms. Further investigation of the above relationships is warranted to explain these phenomena, and establish theoretical explanations underlying sense of agency.

A global pause generates nonselective response inhibition during selective stopping

Publisher: Oxford University Press (OUP)

Date: 07-2023

DOI: 10.1093/CERCOR/BHAD239

Abstract: Selective response inhibition may be required when stopping a part of a multicomponent action. A persistent response delay (stopping-interference effect) indicates nonselective response inhibition during selective stopping. This study aimed to elucidate whether nonselective response inhibition is the consequence of a global pause process during attentional capture or specific to a nonselective cancel process during selective stopping. Twenty healthy human participants performed a bimanual anticipatory response inhibition paradigm with selective stop and ignore signals. Frontocentral and sensorimotor beta-bursts were recorded with electroencephalography. Corticomotor excitability and short-interval intracortical inhibition in primary motor cortex were recorded with transcranial magnetic stimulation. Behaviorally, responses in the non-signaled hand were delayed during selective ignore and stop trials. The response delay was largest during selective stop trials and indicated that stopping-interference could not be attributed entirely to attentional capture. A stimulus-nonselective increase in frontocentral beta-bursts occurred during stop and ignore trials. Sensorimotor response inhibition was reflected in maintenance of beta-bursts and short-interval intracortical inhibition relative to disinhibition observed during go trials. Response inhibition signatures were not associated with the magnitude of stopping-interference. Therefore, nonselective response inhibition during selective stopping results primarily from a nonselective pause process but does not entirely account for the stopping-interference effect.

Selective Inhibition of Movement

Publisher: American Physiological Society

Date: 03-2007

DOI: 10.1152/JN.01284.2006

Abstract: In studies of volitional inhibition, successful task performance usually requires the prevention of all movement. In reality, movements are selectively prevented in the presence of global motor output. The aim of this study was to investigate the ability to prevent one movement while concurrently executing another, referred to as selective inhibition. In two experiments, participants released switches with either their index and middle fingers (unimanual) or their left and right index fingers (bimanual) to stop two moving indicators at a fixed target (Go trials). Stop trials occurred when either one or both indicators automatically stopped before reaching the target, signaling that prevention of the prepared movement was required. Stop All and selective Stop trials were randomly interspersed among more frequently occurring Go trials. We found that selective inhibition is harder to perform than nonselective inhibition, for both unimanual and bimanual task contexts. During selective inhibition trials, lift time of the responding digit was delayed in both experiments by ≤100 ms, demonstrating the generality of the result. A nonselective neural inhibitory pathway may temporarily “brake” the required response, followed by selective excitation of the to-be-moved digit's cortical representation. After selective inhibition trials, there were persistent asynchronies between finger lift times of subsequent Go trials. The persistent effects reflect the behavioral consequences of nonspecific neural inhibition combined with selective neural disinhibition.

Functional potential in chronic stroke patients depends on corticospinal tract integrity

Publisher: Oxford University Press (OUP)

Date: 21-11-2006

DOI: 10.1093/BRAIN/AWL333

Abstract: Determining whether a person with stroke has reached their full potential for recovery is difficult. While techniques such as transcranial magnetic stimulation (TMS) and MRI have some prognostic value, their role in rehabilitation is undefined. This study used TMS and MRI to determine which factors predict functional potential, defined as an in idual's capacity for further functional improvement at least 6 months following stroke. We studied 21 chronic stroke patients with upper limb impairment. The functional integrity of the corticospinal tracts (CSTs) was assessed using TMS and functional MRI. The presence or absence of motor-evoked responses (MEPs) to TMS in the affected upper limb, and the lateralization of cortical activity during affected hand use were determined. The structural integrity of the CST was assessed using MRI, and diffusion tensor imaging was used to measure the asymmetry in fractional anisotropy (FA) of the internal capsules. A multiple linear regression analysis was performed, to predict both clinical score at inception and change in clinical score for 17 patients who completed a 30 day programme of motor practice with the affected upper limb. The main findings were that in patients with MEPs, meaningful gains were still possible 3 years after stroke, although the capacity for improvement declined with time. In patients without MEPs, functional potential declines with increasing CST disruption, with no meaningful gains possible if FA asymmetry exceeds a value of 0.25. This study is the first to demonstrate the complementary nature of TMS and MRI techniques in predicting functional potential in chronic stroke patients. An algorithm is proposed for the selection of in idualized rehabilitation strategies, based on the prediction of functional potential. These strategies could include neuromodulation using a range of emerging techniques, to prime the motor system for a plastic response to rehabilitation.

The fall and rise of corticomotor excitability with cancellation and reinitiation of prepared action

Publisher: American Physiological Society

Date: 12-2014

DOI: 10.1152/JN.00366.2014

Abstract: The sudden cancellation of a motor action, known as response inhibition (RI), is fundamental to human motor behavior. The behavioral selectivity of RI can be studied by cueing cancellation of only a subset of a planned response, which markedly delays the remaining executed components. The present study examined neurophysiological mechanisms that may contribute to these delays. In two experiments, human participants received single- and paired-pulse transcranial magnetic stimulation while performing a bimanual anticipatory response task. Participants performed most trials bimanually (Go trials) and were sometimes cued to cancel the response with one hand while responding with the other (Partial trials). Motor evoked potentials were recorded from left first dorsal interosseous (FDI) as a measure of corticomotor excitability (CME) during Go and Partial trials. CME was temporally modulated during Partial trials in a manner that reflected anticipation, suppression, and subsequent initiation of a reprogrammed response. There was an initial increase in CME, followed by suppression 175 ms after the stop signal, even though the left hand was not cued to stop. A second increase in excitability occurred prior to the (delayed) response. We propose an activation threshold model to account for nonselective RI. To investigate the inhibitory component of our model, we investigated short-latency intracortical inhibition (sICI), but results indicated that sICI cannot fully explain the observed temporal modulation of CME. These neurophysiological and behavioural results indicate that the default mode for reactive partial cancellation is suppression of a unitary response, followed by response reinitiation with an inevitable time delay.

The Influence of Primary Motor Cortex Inhibition on Upper Limb Impairment and Function in Chronic Stroke: A Multimodal Study

Publisher: SAGE Publications

Date: 02-2019

DOI: 10.1177/1545968319826052

Abstract: Background. Stroke is a leading cause of adult disability owing largely to motor impairment and loss of function. After stroke, there may be abnormalities in γ-aminobutyric acid (GABA)-mediated inhibitory function within primary motor cortex (M1), which may have implications for residual motor impairment and the potential for functional improvements at the chronic stage. Objective. To quantify GABA neurotransmission and concentration within ipsilesional and contralesional M1 and determine if they relate to upper limb impairment and function at the chronic stage of stroke. Methods. Twelve chronic stroke patients and 16 age-similar controls were recruited for the study. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Threshold tracking paired-pulse transcranial magnetic stimulation protocols were used to examine short- and long-interval intracortical inhibition and late cortical disinhibition. Magnetic resonance spectroscopy was used to evaluate GABA concentration. Results. Short-interval intracortical inhibition was similar between patients and controls ( P = .10). Long-interval intracortical inhibition was greater in ipsilesional M1 compared with controls ( P .001). Patients who did not exhibit late cortical disinhibition in ipsilesional M1 were those with greater upper limb impairment and worse function ( P = .002 and P = .017). GABA concentration was lower within ipsilesional ( P = .009) and contralesional ( P = .021) M1 compared with controls, resulting in an elevated excitation-inhibition ratio for patients. Conclusion. These findings indicate that ipsilesional and contralesional M1 GABAergic inhibition are altered in this small cohort of chronic stroke patients. Further study is warranted to determine how M1 inhibitory networks might be targeted to improve motor function.

Proportional recovery after stroke depends on corticomotor integrity

Publisher: Wiley

Date: 17-11-2015

DOI: 10.1002/ANA.24472

Abstract: For most patients, resolution of upper limb impairment during the first 6 months poststroke is 70% of the maximum possible. We sought to identify candidate mechanisms of this proportional recovery. We hypothesized that proportional resolution of upper limb impairment depends on ipsilesional corticomotor pathway function, is mirrored by proportional recovery of excitability in this pathway, and is unaffected by upper limb therapy dose. Upper limb impairment was measured in 93 patients at 2, 6, 12, and 26 weeks after first-ever ischemic stroke. Motor evoked potentials (MEPs) and motor threshold were recorded from extensor carpi radialis using transcranial magnetic stimulation, and fractional anisotropy (FA) in the posterior limbs of the internal capsules was determined with diffusion-weighted magnetic resonance imaging. Initial impairment score, presence of MEPs and FA asymmetry were the only predictors of impairment resolution, indicating a key role for corticomotor tract function. By 12 weeks, upper limb impairment resolved by 70% in patients with MEPs regardless of their initial impairment, and ipsilesional rest motor threshold also resolved by 70%. Resolution of impairment was insensitive to upper limb therapy dose. These findings indicate that upper limb impairment resolves by 70% of the maximum possible, regardless of initial impairment, but only for patients with intact corticomotor function. Impairment resolution seems to reflect spontaneous neurobiological processes that involve the ipsilesional corticomotor pathway. A better understanding of these mechanisms could lead to interventions that increase resolution of impairment above 70%.

Proactive modulation of long-interval intracortical inhibition during response inhibition

Publisher: American Physiological Society

Date: 08-2016

DOI: 10.1152/JN.00144.2016

Abstract: Daily activities often require sudden cancellation of preplanned movement, termed response inhibition. When only a subcomponent of a whole response must be suppressed (required here on Partial trials), the ensuing component is markedly delayed. The neural mechanisms underlying partial response inhibition remain unclear. We hypothesized that Partial trials would be associated with nonselective corticomotor suppression and that GABA B receptor-mediated inhibition within primary motor cortex might be responsible for the nonselective corticomotor suppression contributing to Partial trial response delays. Sixteen right-handed participants performed a bimanual anticipatory response inhibition task while single- and paired-pulse transcranial magnetic stimulation was delivered to elicit motor evoked potentials in the left first dorsal interosseous muscle. Lift times, litude of motor evoked potentials, and long-interval intracortical inhibition were examined across the different trial types (Go, Stop-Left, Stop-Right, Stop-Both). Go trials produced a tight distribution of lift times around the target, whereas those during Partial trials (Stop-Left and Stop-Right) were substantially delayed. The modulation of motor evoked potential litude during Stop-Right trials reflected anticipation, suppression, and subsequent reinitiation of movement. Importantly, suppression was present across all Stop trial types, indicative of a “default” nonselective inhibitory process. Compared with blocks containing only Go trials, inhibition increased when Stop trials were introduced but did not differ between trial types. The amount of inhibition was positively correlated with lift times during Stop-Right trials. Tonic levels of inhibition appear to be proactively modulated by task context and influence the speed at which unimanual responses occur after a nonselective “brake” is applied.

Chronic stroke sensorimotor impairment is related to smaller hippocampal volumes: An ENIGMA analysis

Publisher: Cold Spring Harbor Laboratory

Date: 28-10-2021

DOI: 10.1101/2021.10.26.465924

Abstract: Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippoc us is involved in sensorimotor behavior but has not been widely studied within the context of post-stroke upper limb sensorimotor impairment. The hippoc us is vulnerable to secondary degeneration after stroke, and damage to this region could further weaken sensorimotor circuits, leading to greater chronic sensorimotor impairment. The purpose of this study was to investigate the cross-sectional association between non-lesioned hippoc al volume and upper limb sensorimotor impairment in people with chronic stroke. We hypothesized that smaller ipsilesional hippoc al volumes would be associated with worse upper-limb sensorimotor impairment. Cross-sectional T1-weighted brain MRIs were pooled from 357 participants at the chronic stage after stroke ( days post-stroke) compiled from 18 research cohorts worldwide in the ENIGMA Stroke Recovery Working Group (age: median = 61 years, interquartile range = 18, range = 23-93 135 women and 222 men). Sensorimotor impairment was estimated from the Fugl-Meyer Assessment of Upper Extremity scores. Robust mixed-effects linear models were used to test associations between post-stroke sensorimotor impairment and hippoc al volumes (ipsilesional and contralesional separately Bonferroni-corrected, p - value 0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. We also performed an exploratory analysis to test whether sex differences influence the relationship between sensorimotor impairment and hippoc al volume. Upper limb sensorimotor impairment was positively associated with ipsilesional ( p = 0.005 d = 0.33) but not contralesional ( p = 0.96 d = 0.01) hippoc al volume, such that impairment was worse for participants with smaller ipsilesional hippoc al volume. This association remained significant independent of lesion volume or other covariates ( p = 0.001 d = 0.36). Evidence indicates an interaction between sensorimotor impairment and sex for both ipsilesional ( p = 0.008 d = −0.29) and contralesional ( p = 0.006 d = −0.30) hippoc al volumes, whereby women showed progressively worsening sensorimotor impairment with smaller hippoc al volumes compared to men. The present study has identified a novel association between chronic post-stroke sensorimotor impairment and ipsilesional, but not contralesional, hippoc al volume. This finding was not due to lesion size and may be stronger in women. We also provide supporting evidence that smaller hippoc al volume post-stroke is likely a consequence of ipsilesional damage, which could provide a link between vascular disease and other disorders, such as dementia.

Excitability changes in human forearm corticospinal projections and spinal reflex pathways during rhythmic voluntary movement of the opposite limb

Publisher: Wiley

Date: 29-10-2004

DOI: 10.1113/JPHYSIOL.2004.069088

Task-Dependent Modulation of Inputs to Proximal Upper Limb Following Transcranial Direct Current Stimulation of Primary Motor Cortex

Publisher: American Physiological Society

Date: 05-2010

DOI: 10.1152/JN.01046.2009

Abstract: Cathodal transcranial DC stimulation (c-tDCS) suppresses excitability of primary motor cortex (M1) controlling contralateral hand muscles. This study assessed whether c-tDCS would have similar effects on ipsi- and contralateral M1 projections to a proximal upper limb muscle. Transcranial magnetic stimulation (TMS) of left M1 was used to elicit motor evoked potentials (MEPs) in the left and right infraspinatus (INF) muscle immediately before and after c-tDCS of left M1, and at 20 and 40 min, post-c-tDCS. TMS was delivered as participants preactivated each INF in isolation (left, right) or both INF together (bilateral). After c-tDCS, ipsilateral MEPs in left INF and contralateral MEPs in right INF were suppressed in the left task but not in the bilateral or right tasks, indicative of task-dependent modulation. Ipsilateral silent period duration in the left INF was reduced after c-tDCS, indicative of altered transcallosal inhibition. These findings may have implications for the use of tDCS as an adjunct to therapy for the proximal upper limb after stroke.

Dopamine Gene Profiling to Predict Impulse Control and Effects of Dopamine Agonist Ropinirole

Publisher: MIT Press - Journals

Date: 07-2016

DOI: 10.1162/JOCN_A_00946

Abstract: Dopamine agonists can impair inhibitory control and cause impulse control disorders for those with Parkinson disease (PD), although mechanistically this is not well understood. In this study, we hypothesized that the extent of such drug effects on impulse control is related to specific dopamine gene polymorphisms. This double-blind, placebo-controlled study aimed to examine the effect of single doses of 0.5 and 1.0 mg of the dopamine agonist ropinirole on impulse control in healthy adults of typical age for PD onset. Impulse control was measured by stop signal RT on a response inhibition task and by an index of impulsive decision-making on the Balloon Analogue Risk Task. A dopamine genetic risk score quantified basal dopamine neurotransmission from the influence of five genes: catechol-O-methyltransferase, dopamine transporter, and those encoding receptors D1, D2, and D3. With placebo, impulse control was better for the high versus low genetic risk score groups. Ropinirole modulated impulse control in a manner dependent on genetic risk score. For the lower score group, both doses improved response inhibition (decreased stop signal RT) whereas the lower dose reduced impulsiveness in decision-making. Conversely, the higher score group showed a trend for worsened response inhibition on the lower dose whereas both doses increased impulsiveness in decision-making. The implications of the present findings are that genotyping can be used to predict impulse control and whether it will improve or worsen with the administration of dopamine agonists.

Biomarker-based patient selection improves stroke rehabilitation trial efficiency

Publisher: Cold Spring Harbor Laboratory

Date: 02-11-2018

DOI: 10.1101/459776

Abstract: Inter-subject variability complicates trials of novel stroke rehabilitation therapies, particularly in the sub-acute phase after stroke. We tested whether selecting patients using motor evoked potential (MEP) status, a physiological biomarker of motor system function, could improve trial efficiency. A retrospective analysis of data from 207 patients (103 women, mean (SD) 70.6 (15.1) years) was used to estimate s le sizes and recruitment rates required to detect a 7-point difference between hypothetical control and treatment groups in upper-limb Fugl-Meyer and Action Research Arm Test scores at 90 days post-stroke. Analyses were carried out for the full s le and for subsets defined by motor evoked potential (MEP) status. Selecting patients according to MEP status reduced the required s le size by 75% compared to an unselected s le. The estimated time needed to recruit the required s le was also reduced by 72% for patients with MEPs, and was increased by 2-3-fold for patients without MEPs. Using biomarkers to select patients can improve stroke rehabilitation trial efficiency by reducing the s le size and recruitment time needed to detect a clinically meaningful effect of the tested intervention.

Contralesional Hemisphere Control of the Proximal Paretic Upper Limb following Stroke

Publisher: Oxford University Press (OUP)

Date: 12-2011

DOI: 10.1093/CERCOR/BHR344

Fatigue influences the recruitment, but not structure, of muscle synergies

Publisher: Cold Spring Harbor Laboratory

Date: 19-01-2018

DOI: 10.1101/250522

Abstract: The development of fatigue elicits multiple adaptations from the neuromuscular system. Muscle synergies are common patterns of neuromuscular activation that have been proposed as the building blocks of human movement. We wanted to identify possible adaptations of muscle synergies to the development of fatigue in the upper limb. Recent studies have reported that synergy structure remains invariant during the development of fatigue, but these studies did not examine isolated synergies. We propose a novel approach to characterize synergy adaptations to fatigue by taking advantage of the spatial tuning of synergies. This approach allows improved identification of changes to in idual synergies that might otherwise be confounded by changing contributions of overlapping synergies. To analyse upper limb synergies we applied non-negative matrix factorization to 14 EMG signals from muscles of 11 participants performing isometric contractions. A preliminary multidirectional task was used to identify synergy directional tuning. A subsequent fatiguing task was designed to fatigue the participants in their synergies’ preferred directions. Both tasks provided virtual reality feedback of the applied force direction and magnitude, and were performed at 40% of each participant’s maximal voluntary force. Five epochs were analysed throughout the fatiguing task to identify progressive changes of EMG litude, median frequency, synergy structure, and activation coefficients. Three to four synergies were sufficient to account for the variability contained in the original data. Synergy structure was conserved with fatigue, but interestingly synergy activation coefficients decreased on average by 24.5% with fatigue development. EMG litude did not change systematically with fatigue, whereas EMG median frequency consistently decreased across all muscles. These results support the notion of a neuromuscular modular organization as the building blocks of human movement, with adaptations to synergy recruitment occurring with fatigue. When synergy tuning properties are considered, the reduction of activation of muscle synergies may be a reliable marker to identify fatigue.

Primary Motor Cortex Excitability During Recovery After Stroke: Implications for Neuromodulation

Publisher: Elsevier BV

Date: 11-2015

DOI: 10.1016/J.BRS.2015.06.015

Abstract: Non-invasive brain stimulation techniques may be useful adjuvants to promote recovery after stroke. They are typically used to facilitate ipsilesional cortical excitability directly, or indirectly by suppressing contralesional cortical excitability and reducing interhemispheric inhibition from the contralesional to ipsilesional hemisphere. However, most of the evidence for this approach comes from studies of patients at the chronic stage of recovery. We hypothesized that corticomotor excitability and interhemispheric inhibition would initially be asymmetric, with greater interhemispheric inhibition from contralesional to ipsilesional M1. We also hypothesized that balancing of corticomotor excitability and interhemispheric inhibition would be associated with greater improvements in paretic upper-limb impairment and function. We conducted a retrospective analysis of longitudinal data collected from 46 patients during the first six months after stroke. Transcranial magnetic stimulation was used to measure rest motor threshold, stimulus-response curves, and ipsilateral silent periods from the extensor carpi radialis muscles of both upper limbs. Analyses of variance and linear regression modeling were used to evaluate the effect of time on corticomotor excitability and interhemispheric inhibition in both hemispheres, and associations between these effects and improvements in paretic upper-limb impairment and function. All participants had subcortical damage and only two had motor cortex involvement. As expected, ipsilesional corticomotor excitability was initially suppressed and increased over time, and this increase was associated with improved upper-limb impairment and function. However, interhemispheric inhibition was symmetrical and stable over time, and there was no evidence for a decrease in contralesional corticomotor excitability. Neuromodulation interventions applied during spontaneous recovery may be more beneficial if they facilitate ipsilesional corticomotor excitability directly.

Transcranial Direct Current Stimulation Improves Ipsilateral Selective Muscle Activation in a Frequency Dependent Manner

Publisher: Public Library of Science (PLoS)

Date: 27-03-2015

DOI: 10.1371/JOURNAL.PONE.0122434

Normalizing Motor Cortex Representations in Focal Hand Dystonia

Publisher: Oxford University Press (OUP)

Date: 12-12-2008

DOI: 10.1093/CERCOR/BHN224

Abstract: Task-specific focal dystonia is thought to have a neurological basis where stereotypical synchronous inputs and maladaptive plasticity play a role. As afferent input is a powerful driver of cortical reorganization, we propose that a period of asynchronous afferent stimulation may reverse maladaptive cortical changes and alleviate symptoms. Using transcranial magnetic stimulation (TMS), 3 hand muscles were mapped in 10 dystonics and 10 healthy controls. Mapping occurred before and after 1 h of nonassociative stimulation (NAS) to first dorsal interosseous (FDI) and abductor pollicis brevis (APB). Participants performed grip lift, handwriting, and cyclic drawing before and after NAS. Prior to NAS, dystonics had larger maps, and the centers of gravity (CoGs) of the FDI and APB maps were closer together. Dystonics demonstrated impairments in grip-lift, handwriting, and cyclic drawing tasks. Following NAS, map size was reduced in all muscles in dystonic participants and FDI and APB CoGs moved further apart. Among dystonics, NAS produced a reduction in movement variability during cyclic drawing. Thus, 1 h of NAS can reduce the magnitude, and increase the separation, of TMS representational maps. We suggest that these changes reflect some normalization of the representational abnormalities seen in focal dystonia and provide initial, limited evidence that such changes are associated with improvements in circle drawing.

Comparing anticipatory and stop-signal response inhibition with a novel, open-source selective stopping toolbox

Publisher: Springer Science and Business Media LLC

Date: 13-01-2023

DOI: 10.1007/S00221-022-06539-9

Abstract: Response inhibition is essential for terminating inappropriate actions and, in some cases, may be required selectively. Selective stopping can be investigated with multicomponent anticipatory or stop-signal response inhibition paradigms. Here we provide a freely available open-source Selective Stopping Toolbox (SeleST) to investigate selective stopping using either anticipatory or stop-signal task variants. This study aimed to evaluate selective stopping between the anticipatory and stop-signal variants using SeleST and provide guidance to researchers for future use. Forty healthy human participants performed bimanual anticipatory response inhibition and stop-signal tasks in SeleST. Responses were more variable and slowed to a greater extent during the stop-signal than in the anticipatory paradigm. However, the stop-signal paradigm better conformed to the assumption of the independent race model of response inhibition. The expected response delay during selective stop trials was present in both variants. These findings indicate that selective stopping can successfully be investigated with either anticipatory or stop-signal paradigms in SeleST. We propose that the anticipatory paradigm should be used when strict control of response times is desired, while the stop-signal paradigm should be used when it is desired to estimate stop-signal reaction time with the independent race model. Importantly, the dual functionality of SeleST allows researchers flexibility in paradigm selection when investigating selective stopping.

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 16-05-2023

DOI: 10.1212/WNL.0000000000207219

Abstract: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (β = 0.21 95% CI 0.04–0.38, p = 0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (β = −0.28 95% CI −0.41 to −0.15, p 0.001) and across multiple domains of function (β = −0.14 95% CI −0.22 to −0.06, p 0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI 3%–58%, p = 0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (odds ratio 1.04, 95% CI 1.01–1.08, p = 0.004). We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets.

Muscle synergies are associated with intermuscular coherence and cortico-synergy coherence in an isometric upper limb task

Publisher: Springer Science and Business Media LLC

Date: 22-09-2023

DOI: 10.1007/S00221-023-06706-6

Cathodal transcranial direct current stimulation suppresses ipsilateral projections to presumed propriospinal neurons of the proximal upper limb

Publisher: American Physiological Society

Date: 05-2011

DOI: 10.1152/JN.01084.2010

Abstract: This study investigated whether cathodal transcranial direct current stimulation (c-tDCS) of left primary motor cortex (M1) modulates excitability of ipsilateral propriospinal premotoneurons (PNs) in healthy humans. Transcranial magnetic stimulation (TMS) of the right motor cortex was used to obtain motor evoked potentials (MEPs) from the left biceps brachii (BB) while participants maintained contraction of the left BB. To examine presumed PN excitability, left BB MEPs were compared with those conditioned by median nerve stimulation (MNS) at the left elbow. Interstimulus intervals between TMS and MNS were set to produce summation at the C3–C4 level of the spinal cord. MNS facilitated BB MEPs elicited at TMS intensities near active motor threshold but inhibited BB MEPs at slightly higher intensities, indicative of putative PN modulation. c-tDCS suppressed the facilitatory and inhibitory effects of MNS. Sham tDCS did not alter either component. There was no effect of c-tDCS and sham tDCS on nonconditioned left BB MEPs or on the ipsilateral silent period of left BB. Right first dorsal interosseous MEPs were suppressed by c-tDCS. These results indicate that M1 c-tDCS can be used to modulate excitability of ipsilateral projections to presumed PNs controlling the proximal arm muscle BB. This technique may hold promise for promoting motor recovery of proximal upper limb function after stroke.

Simon Fraser University

Location: Canada

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University Of Windsor

Location: Canada

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The University Of Auckland

Location: New Zealand

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Linkage - International - Grant ID: LX0667145

Start Date: 2006

End Date: 12-2008

Amount: $10,792.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP200100234

Start Date: 02-2020

End Date: 12-2024

Amount: $543,500.00

Funder: Australian Research Council