Biology subjects

Byblow, W. D.

Publications and source records attributed to Byblow, W. D..

10 recordsLinked to original sources

bioRxiv2023

A global pause generates nonselective response inhibition during selective stopping

1Response 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 ({beta})-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 {beta}-bursts occurred during stop and ignore trials, whilst sensorimotor response inhibition was reflected in maintenance of {beta}-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 Significance statementSelective 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.

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bioRxiv2022

Proactive interhemispheric disinhibition supports response preparation during selective stopping

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. Significance statementResponse 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.

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bioRxiv2022

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

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 brains 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., Alzheimers disease) to stroke.

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bioRxiv2021

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

Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is involved in sensorimotor behavior but has not been widely studied within the context of post-stroke upper limb sensorimotor impairment. The hippocampus 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 hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke. We hypothesized that smaller ipsilesional hippocampal 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 (>180 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 hippocampal 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 hippocampal 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) hippocampal volume, such that impairment was worse for participants with smaller ipsilesional hippocampal 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) hippocampal volumes, whereby women showed progressively worsening sensorimotor impairment with smaller hippocampal volumes compared to men. The present study has identified a novel association between chronic post-stroke sensorimotor impairment and ipsilesional, but not contralesional, hippocampal volume. This finding was not due to lesion size and may be stronger in women. We also provide supporting evidence that smaller hippocampal volume post-stroke is likely a consequence of ipsilesional damage, which could provide a link between vascular disease and other disorders, such as dementia.

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bioRxiv2021

The proportional recovery rule redux: Arguments for its biological and predictive relevance

The proportional recovery rule (PRR) posits that most stroke survivors can expect to reduce a fixed proportion of their motor impairment. As a statistical model, the PRR explicitly relates change scores to baseline values - an approach that has the potential to introduce artifacts and flawed conclusions. We describe approaches that can assess associations between baseline and changes from baseline while avoiding artifacts due either to mathematical coupling or regression to the mean due to measurement error. We also describe methods that can compare different biological models of recovery. Across several real datasets, we find evidence for non-artifactual associations between baseline and change, and support for the PRR compared to alternative models. We conclude that the PRR remains a biologically-relevant model of recovery, and also introduce a statistical perspective that can be used to assess future models.

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bioRxiv2020

Non-lesioned subcortical brain volumes are associated with post-stroke sensorimotor behavior across 28 cohorts worldwide: An ENIGMA Stroke Recovery study

Background and PurposeUp 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. MethodsWe pooled high-resolution T1-weighted MRI brain scans and behavioral data in 828 individuals 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<0.004). 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. ResultsWorse 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). ConclusionsWe 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.

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bioRxiv2019

Muscle synergies are associated with intermuscular coherence in an isometric upper limb task.

To elucidate the underlying physiological mechanism of muscle synergies, we investigated the functional corticomuscular and intermuscular binding during an isometric upper limb task in 14 healthy participants. Cortical activity was recorded using 32-channel encephalography (EEG) and muscle activity using 16-channel electromyography (EMG). Using non-negative matrix factorization (NMF), we calculated muscle synergies from two different tasks. A preliminary multidirectional task was used to identify synergy preferred directions. A subsequent coherence task, consisting of generating forces isometrically in the synergy PDs, was used to assess the functional connectivity properties of synergies. Functional connectivity was estimated using corticomuscular coherence (CMC) and intermuscular coherence (IMC). Overall, we were able to extract four different synergies from the multidirectional task. A significant alpha band IMC was present consistently in all extracted synergies. Moreover, alpha band IMC was higher between muscles with higher weights within a synergy. In contrast, no significant CMC was found between the motor cortex area and synergy muscles. In addition, there is a relationship between a synergy muscle weight and the level of IMC. Our findings suggest the existence of a consistent shared input between muscles of each synergy. Finally, the existence of a shared input onto synergistic muscles within a synergy supports the idea of neurally-derived muscle synergies that build human movement.

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bioRxiv2019

Effects of arm weight support on neuromuscular activation during reaching in chronic stroke patients

To better understand how arm weight support (WS) can be used to alleviate upper limb impairment after stroke, we investigated the effects of WS on muscle activity, muscle synergy expression, and corticomotor excitability (CME) in 13 chronic stroke patients and 6 age-similar healthy controls. For patients, lesion location and corticospinal tract integrity were assessed using magnetic resonance imaging. Upper limb impairment was assessed using the Fugl-Meyer upper extremity assessment with patients categorised as either mild or moderate-severe. Three levels of WS were examined: low=0, medium=50 and high=100 % of full support. Surface EMG was recorded from 8 upper limb muscles, and muscle synergies were decomposed using non-negative matrix factorisation from data obtained during reaching movements to an array of 14 targets using the paretic or dominant arm. Interactions between impairment level and WS were found for the number of targets hit, and EMG measures. Overall, greater WS resulted in lower EMG levels, although the degree of modulation between WS levels was less for patients with moderate-severe compared to mild impairment. Healthy controls expressed more synergies than patients with moderate-severe impairment. Healthy controls and patients with mild impairment showed more synergies with high compared to low weight support. Transcranial magnetic stimulation was used to elicit motor-evoked potentials (MEPs) to which stimulus-response curves were fitted as a measure of corticomotor excitability (CME). The effect of WS on CME varied between muscles and across impairment level. These preliminary findings demonstrate that WS has direct and indirect effects on muscle activity, synergies, and CME and warrants further study in order to reduce upper limb impairment after stroke.

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bioRxiv2018

Biomarker-based patient selection improves stroke rehabilitation trial efficiency

Background and PurposeInter-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.\n\nMethodsA retrospective analysis of data from 207 patients (103 women, mean (SD) 70.6 (15.1) years) was used to estimate sample 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 sample and for subsets defined by motor evoked potential (MEP) status.\n\nResultsSelecting patients according to MEP status reduced the required sample size by 75% compared to an unselected sample. The estimated time needed to recruit the required sample was also reduced by 72% for patients with MEPs, and was increased by 2-3-fold for patients without MEPs.\n\nConclusionsUsing biomarkers to select patients can improve stroke rehabilitation trial efficiency by reducing the sample size and recruitment time needed to detect a clinically meaningful effect of the tested intervention.

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bioRxiv2018

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

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 individual 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 participants maximal voluntary force. Five epochs were analysed throughout the fatiguing task to identify progressive changes of EMG amplitude, 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 amplitude 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.

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