The excitability of ipsilateral motor evoked potentials is not task-specific and spatially distinct from the contralateral motor hotspot.

OBJECTIVE: The role of ipsilateral descending motor pathways in voluntary movement of humans is still a matter of debate, with partly contradictory results. The aim of our study therefore was to examine the excitability of ipsilateral motor evoked potentials (iMEPs) regarding site and the specificity for unilateral and bilateral elbow flexion extension tasks. METHODS: MR-navigated transcranial magnetic stimulation mapping of the dominant hemisphere was performed in twenty healthy participants during tonic unilateral (iBB), bilateral homologous (bBB) or bilateral antagonistic elbow flexion-extension (iBB-cAE), the map center of gravity (CoG) and iMEP area from BB were obtained. RESULTS: The map CoG of the ipsilateral BB was located more anterior-laterally than the hotspot of the contralateral BB within the primary motor cortex, with a significant difference in CoG in iBB and iBB-cAE, but not bBB compared to the hotspot for the contralateral BB (each p < 0.05). However, different tasks had no effect on the size of the iMEPs. CONCLUSION: Our data demonstrated that excitability of ipsilateral and contralateral MEP differ spatially in a task-specific manner suggesting the involvement of different motor networks within the motor cortex.

Corticomotor pathway function and recovery after stroke: a look back and a way forward.

Stroke is a leading cause of adult disability that results in motor deficits and reduced independence. Regaining independence relies on motor recovery, particularly regaining function of the hand and arm. This review presents evidence from human studies that have used transcranial magnetic stimulation (TMS) to identify neurophysiological mechanisms underlying upper limb motor recovery early after stroke. TMS studies undertaken at the subacute stage after stroke have identified several neurophysiological factors that can drive motor impairment, including membrane excitability, the recruitment of corticomotor neurons, and glutamatergic and GABAergic neurotransmission. However, the inherent variability and subsequent poor reliability of measures derived from motor evoked potentials (MEPs) limit the use of TMS for prognosis at the individual patient level. Currently, prediction tools that provide the most accurate information about upper limb motor outcomes for individual patients early after stroke combine clinical measures with a simple neurophysiological biomarker based on MEP presence or absence, i.e. MEP status. Here, we propose a new compositional framework to examine MEPs across several upper limb muscles within a threshold matrix. The matrix can provide a more comprehensive view of corticomotor function and recovery after stroke by quantifying the evolution of subthreshold and suprathreshold MEPs through compositional analyses. Our contention is that subthreshold responses might be the most sensitive to reduced output of corticomotor neurons, desynchronized firing of the remaining neurons, and myelination processes that occur early after stroke. Quantifying subthreshold responses might provide new insights into post-stroke neurophysiology and improve the accuracy of prediction of upper limb motor outcomes.

Applications of Repetitive Transcranial Magnetic Stimulation to Improve Upper Limb Motor Performance After Stroke: A Systematic Review.

BACKGROUND: Noninvasive brain stimulation (NIBS) is a promising technique for improving upper limb motor performance post-stroke. Its application has been guided by the interhemispheric competition model and typically involves suppression of contralesional motor cortex. However, the bimodal balance recovery model prompts a more tailored application of NIBS based on ipsilesional corticomotor function. OBJECTIVE: To review and assess the application of repetitive transcranial magnetic stimulation (rTMS) protocols that aimed to improve upper limb motor performance after stroke. METHODS: A PubMed search was conducted for studies published between 1st January 2005 and 1st November 2022 using rTMS to improve upper limb motor performance of human adults after stroke. Studies were grouped according to whether facilitatory or suppressive rTMS was applied to the contralesional hemisphere. RESULTS: Of the 492 studies identified, 70 were included in this review. Only 2 studies did not conform to the interhemispheric competition model, and facilitated the contralesional hemisphere. Only 21 out of 70 (30%) studies reported motor evoked potential (MEP) status as a biomarker of ipsilesional corticomotor function. Around half of the studies (37/70, 53%) checked whether rTMS had the expected effect by measuring corticomotor excitability (CME) after application. CONCLUSION: The interhemispheric competition model dominates the application of rTMS post-stroke. The majority of recent and current studies do not consider bimodal balance recovery model for the application of rTMS. Evaluating CME after the application rTMS could confirm that the intervention had the intended neurophysiological effect. Future studies could select patients and apply rTMS protocols based on ipsilesional MEP status.

Reliability of a TMS-derived threshold matrix of corticomotor function.

Transcranial magnetic stimulation (TMS) studies typically focus on suprathreshold motor evoked potentials (MEPs), overlooking small MEPs representing subthreshold corticomotor pathway activation. Assessing subthreshold excitability could provide insights into corticomotor pathway integrity and function, particularly in neurological conditions like stroke. The aim of the study was to examine the test-retest reliability of metrics derived from a novel compositional analysis of MEP data from older adults. The study also compared the composition between the dominant (D) and non-dominant (ND) sides and explored the association between subthreshold responses and resting motor threshold. In this proof-of-concept study, 23 healthy older adults participated in two identical experimental sessions. Stimulus-response (S-R) curves and threshold matrices were constructed using single-pulse TMS across intensities to obtain MEPs in four upper limb muscles. S-R curves had reliable slopes for every muscle (Intraclass Correlation Coefficient range = 0.58-0.88). Subliminal and suprathreshold elements of the threshold matrix showed good-excellent reliability (D subliminal ICC = 0.83; ND subliminal ICC = 0.79; D suprathreshold ICC = 0.92; ND suprathreshold ICC = 0.94). By contrast, subthreshold elements of the matrix showed poor reliability, presumably due to a floor effect (D subthreshold ICC = 0.39; ND subthreshold ICC = 0.05). No composition differences were found between D and ND sides (suprathreshold BF01 = 3.85; subthreshold BF01 = 1.68; subliminal BF01 = 3.49). The threshold matrix reliably assesses subliminal and suprathreshold MEPs in older adults. Further studies are warranted to evaluate the utility of compositional analyses for assessing recovery of corticomotor pathway function after neurological injury.

Modulation of ipsilateral motor evoked potentials during bimanual coordination tasks.

Introduction: Ipsilateral motor evoked potentials (iMEPs) are difficult to obtain in distal upper limb muscles of healthy participants but give a direct insight into the role of ipsilateral motor control. Methods: We tested a new high-intensity double pulse transcranial magnetic stimulation (TMS) protocol to elicit iMEPs in wrist extensor and flexor muscles during four different bimanual movements (cooperative-asymmetric, cooperative-symmetric, non-cooperative-asymmetric and non-cooperative-symmetric) in 16 participants. Results: Nine participants showed an iMEP in the wrist extensor in at least 20% of the trials in each of the conditions and were classified as iMEP+ participants. iMEP persistence was greater for cooperative (50.5 ± 28.8%) compared to non-cooperative (31.6 ± 22.1%) tasks but did not differ between asymmetric and symmetric tasks. Area and amplitude of iMEPs were also increased during cooperative (area = 5.41 ± 3.4 mV × ms; amplitude = 1.60 ± 1.09 mV) compared to non-cooperative (area = 3.89 ± 2.0 mV × ms; amplitude = 1.12 ± 0.56 mV) tasks and unaffected by task-symmetry. Discussion: The upregulation of iMEPs during common-goal cooperative tasks shows a functional relevance of ipsilateral motor control in bimanual movements. The paired-pulse TMS protocol is a reliable method to elicit iMEPs in healthy participants and can give new information about neural control of upper limb movements. With this work we contribute to the research field in two main aspects. First, we describe a reliable method to elicit ipsilateral motor evoked potentials in healthy participants which will be useful in further advancing research in the area of upper limb movements. Second, we add new insight into the motor control of bimanual movements. We were able to show an upregulation of bilateral control represented by increased ipsilateral motor evoked potentials in cooperative, object-oriented movements compared to separate bimanual tasks. This result might also have an impact on neurorehabilitation after stroke.

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

To elucidate the underlying physiological mechanisms of muscle synergies, we investigated long-range functional connectivity by cortico-muscular (CMC), intermuscular (IMC) and cortico-synergy (CSC) coherence. Fourteen healthy participants executed an isometric upper limb task in synergy-tuned directions. Cortical activity was recorded using 32-channel electroencephalography (EEG) and muscle activity using 16-channel electromyography (EMG). Using non-negative matrix factorisation (NMF), we calculated muscle synergies from two different tasks. A preliminary multidirectional task was used to identify synergy-preferred directions (PDs). A subsequent coherence task, consisting of generating forces isometrically in the synergy PDs, was used to assess the functional connectivity properties of synergies. Overall, we were able to identify four different synergies from the multidirectional task. A significant alpha band IMC was consistently present in all extracted synergies. Moreover, IMC alpha band was higher between muscles with higher weights within a synergy. Interestingly, CSC alpha band was also significantly higher across muscles with higher weights within a synergy. In contrast, no significant CMC was found between the motor cortex area and synergy muscles. The presence of a shared input onto synergistic muscles within a synergy supports the idea of neurally derived muscle synergies that build human movement. Our findings suggest cortical modulation of some of the synergies and the consequential existence of shared input between muscles within cortically modulated synergies.

A global pause generates nonselective response inhibition during selective stopping.

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.

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

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (ß = 0.21; 95% CI 0.04-0.38, p = 0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (ß = -0.28; 95% CI -0.41 to -0.15, p < 0.001) and across multiple domains of function (ß = -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). DISCUSSION: 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.

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

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.

Proactive Interhemispheric Disinhibition Supports Response Preparation during Selective Stopping.

Response inhibition is essential for terminating inappropriate actions. A substantial response delay may occur in the nonstopped effector when only part of a multieffector action is terminated. This stopping-interference effect has been attributed to nonselective response inhibition processes and can be reduced with proactive cuing. This study aimed to elucidate the role of interhemispheric primary motor cortex (M1-M1) influences during selective stopping with proactive cuing. We hypothesized that stopping-interference would be reduced as stopping certainty increased because of proactive recruitment of interhemispheric facilitation or inhibition when cued to respond or stop, respectively. Twenty-three healthy human participants of either sex 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 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, whereas IHF was not observed in either context. An effector-specific reduction in CME but no reinstatement of IHI was observed when the left hand was cued to stop. These findings indicate that stopping speed and selectivity are better with proactive cueing and that interhemispheric M1-M1 channels modulate inhibitory tone during response preparation to support going but not proactive response inhibition.SIGNIFICANCE STATEMENT Response inhibition is essential for terminating inappropriate actions and, in some cases, may be required for only part of a multieffector action. The present study examined interhemispheric influences between the primary motor cortices during selective stopping with proactive cuing. Stopping selectivity was greater with increased stopping certainty and was marked by proactive adjustments to the hand cued to stop and hand cued to respond separately. Inhibitory interhemispheric influences were released during response preparation but were not directly involved in proactive response inhibition. These findings indicate that between-hand stopping can be selective with proactive cuing, but cue-related improvements are unlikely to reflect the advance engagement of interhemispheric influences between primary motor cortices.

Arguments for the biological and predictive relevance of the proportional recovery rule.

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 arises in many scientific domains but 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 to regression to the mean. We also describe methods that can compare different biological models of recovery. Across several real datasets in stroke recovery, we find evidence for non-artifactual associations between baseline and change, and support for the PRR compared to alternative models. We also introduce a statistical perspective that can be used to assess future models. We conclude that the PRR remains a biologically relevant model of stroke recovery.

Intracortical facilitation and inhibition in human primary motor cortex during motor skill acquisition.

The primary motor cortex (M1) is critical for movement execution, but its role in motor skill acquisition remains elusive. Here, we examine the role of M1 intracortical circuits during skill acquisition. Paired-pulse transcranial magnetic stimulation (TMS) paradigms of short-interval intracortical facilitation (SICF) and inhibition (SICI) were used to assess excitatory and inhibitory circuits, respectively. We hypothesised that intracortical facilitation and inhibition circuits in M1 would be modulated to support acquisition of a novel visuomotor skill. Twenty-two young, neurologically healthy adults trained with their nondominant hand on a skilled and non-skilled sequential visuomotor isometric finger abduction task. Electromyographic recordings were obtained from the nondominant first dorsal interosseous (FDI) muscle. Corticomotor excitability, SICF, and SICI were examined before, at the midway point, and after the 10-block motor training. SICI was assessed using adaptive threshold-hunting procedures. Task performance improved after the skilled, but not non-skilled, task training, which likely reflected the increase in movement speed during training. The amplitudes of late SICF peaks were modulated with skilled task training. There was no modulation of the early SICF peak, SICI, and corticomotor excitability with either task training. There was also no association between skill acquisition and SICF or SICI. The findings indicate that excitatory circuitries responsible for the generation of late SICF peaks, but not the early SICF peak, are modulated in motor skill acquisition for a sequential visuomotor isometric finger abduction task.

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis.

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; ß=0.16) but not contralesional (P=0.96; ß=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; ß=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; ß=-0.26) and contralesional (P=0.006; ß=-0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; ß=-0.21) and extent of sensorimotor damage (P=0.003; ß=-0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.

Stopping Interference in Response Inhibition: Behavioral and Neural Signatures of Selective Stopping.

Response inhibition is an essential aspect of cognitive control that is necessary for terminating inappropriate preplanned or ongoing responses. Response-selective stopping represents a complex form of response inhibition where only a subcomponent of a multicomponent action must be terminated. In this context, a substantial response delay emerges on unstopped effectors after the cued effector is successfully stopped. This response delay has been termed the stopping interference effect. Converging lines of evidence indicate that this effect results from a global response inhibition mechanism that is recruited regardless of the stopping context. However, behavioral observations reveal that the stopping interference effect may not always occur during selective stopping. This review summarizes the behavioral and neural signatures of response inhibition during selective stopping. An overview of selective stopping contexts and the stopping interference effect is provided. A "restart" model of selective stopping is expanded on in light of recent neurophysiological evidence of selective and nonselective response inhibition. Factors beyond overt action cancellation that contribute to the stopping interference effect are discussed. Finally, a pause-then-cancel model of action stopping is presented as a candidate framework to understand stopping interference during response-selective stopping. The extant literature indicates that stopping interference may result from both selective and nonselective response inhibition processes, which can be amplified or attenuated by response conflict, task familiarity, and functional coupling.

Investigating the structure-function relationship of the corticomotor system early after stroke using machine learning.

BACKGROUND: Motor outcomes after stroke can be predicted using structural and functional biomarkers of the descending corticomotor pathway, typically measured using magnetic resonance imaging and transcranial magnetic stimulation, respectively. However, the precise structural determinants of intact corticomotor function are unknown. Identifying structure-function links in the corticomotor pathway could provide valuable insight into the mechanisms of post-stroke motor impairment. This study used supervised machine learning to classify upper limb motor evoked potential status using MRI metrics obtained early after stroke. METHODS: Retrospective data from 91 patients (49 women, age 35-97 years) with moderate to severe upper limb weakness within a week after stroke were included in this study. Support vector machine classifiers were trained using metrics from T1- and diffusion-weighted MRI to classify motor evoked potential status, empirically measured using transcranial magnetic stimulation. RESULTS: Support vector machine classification of motor evoked potential status was 81% accurate, with false positives more common than false negatives. Important structural MRI metrics included diffusion anisotropy asymmetry in the supplementary and pre-supplementary motor tracts, maximum cross-sectional lesion overlap in the sensorimotor tract and ventral premotor tract, and mean diffusivity asymmetry in the posterior limbs of the internal capsule. INTERPRETATIONS: MRI measures of corticomotor structure are good but imperfect predictors of corticomotor function. Residual corticomotor function after stroke depends on both the extent of cross-sectional macrostructural tract damage and preservation of white-matter microstructural integrity. Analysing the corticomotor pathway using a multivariable MRI approach across multiple tracts may yield more information than univariate biomarker analyses.

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain-behavior relationships after stroke.

The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large-scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided.

Fast Outcome Categorization of the Upper Limb After Stroke.

BACKGROUND AND PURPOSE: The ARAT (Action Research Arm Test) has been used to classify upper limb motor outcome after stroke in 1 of 3, 4, or 5 categories. The COVID-19 pandemic has encouraged the development of assessments that can be performed quickly and remotely. The aim of this study was to derive and internally validate decision trees for categorizing upper limb motor outcomes at the late subacute and chronic stages of stroke using a subset of ARAT tasks. METHODS: This study retrospectively analyzed ARAT scores obtained in-person at 3 months poststroke from 333 patients. In-person ARAT scores were used to categorize patients' 3-month upper limb outcome using classification systems with 3, 4, and 5 outcome categories. Individual task scores from in-person assessments were then used in classification and regression tree analyses to determine subsets of tasks that could accurately categorize upper limb outcome for each of the 3 classification systems. The decision trees developed using 3-month ARAT data were also applied to in-person ARAT data obtained from 157 patients at 6 months poststroke. RESULTS: The classification and regression tree analyses produced decision trees requiring 2 to 4 ARAT tasks. The overall accuracy of the cross-validated decision trees ranged from 87.7% (SE, 1.0%) to 96.7% (SE, 2.0%). Accuracy was highest when classifying patients into one of 3 outcome categories and lowest for 5 categories. The decision trees are referred to as FOCUS (Fast Outcome Categorization of the Upper Limb After Stroke) assessments and they remained accurate for 6-month poststroke ARAT scores (overall accuracy range 83.4%-91.7%). CONCLUSIONS: A subset of ARAT tasks can accurately categorize upper limb motor outcomes after stroke. Future studies could investigate the feasibility and accuracy of categorizing outcomes using the FOCUS assessments remotely via video call.

Decoupling countermands nonselective response inhibition during selective stopping.

Response inhibition is essential for goal-directed behavior within dynamic environments. Selective stopping is a complex form of response inhibition where only part of a multieffector response must be cancelled. A substantial response delay emerges on unstopped effectors when a cued effector is successfully stopped. This stopping-interference effect is indicative of nonselective response inhibition during selective stopping, which may, in part, be a consequence of functional coupling. The present study examined selective stopping of (de)coupled bimanual responses in healthy human participants of either sex. Participants performed synchronous and asynchronous versions of an anticipatory stop-signal paradigm across two sessions while mu (µ) and beta (ß) rhythms were measured with electroencephalography. Results showed that responses were behaviorally decoupled during asynchronous go trials and the extent of response asynchrony was associated with lateralized sensorimotor µ- and ß-desynchronization during response preparation. Selective stopping produced a stopping-interference effect and was marked by a nonselective increase and subsequent rebound in prefrontal and sensorimotor ß. In support of the coupling account, stopping-interference was smaller during selective stopping of asynchronous responses and negatively associated with the magnitude of decoupling. However, the increase in sensorimotor ß during selective stopping was equivalent between the stopped and unstopped hand irrespective of response synchrony. Overall, the findings demonstrate that decoupling facilitates selective stopping after a global pause process and emphasizes the importance of considering the influence of both the go and stop context when investigating response inhibition.NEW & NOTEWORTHY Humans rely on their ability to stop preplanned or ongoing movements. The present study identified neural signatures of response preparation and inhibition from electroencephalography during selective stopping of coupled and decoupled bimanual responses. Stopping was more selective for decoupled compared with coupled responses and supported by lateralization of sensorimotor mu and beta power during response preparation. These findings demonstrate that decoupling may have functional significance for understanding cognitive control in the form of selective stopping.

Dopamine genetic risk score predicts impulse control behaviors in Parkinson's disease.

INTRODUCTION: Up to 40% of Parkinson's disease patients taking dopamine agonist medication develop impulse control behaviors which can have severe negative consequences. The current study aimed to utilize dopamine genetics to identify patients most at risk of developing these behaviors. METHODS: Demographic, clinical, and genetic data were obtained from the Parkinson's Progression Markers Initiative for de novo patients (n = 327), patients taking dopamine agonists (n = 146), and healthy controls (n = 160). Impulsive behaviors were identified using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease. A dopamine genetic risk score was calculated for each patient according to polymorphisms in genes coding for dopamine D1, D2 and D3 receptors, and catechol-O-methyltransferase. A higher score reflected higher central dopamine neurotransmission. RESULTS: Patients on agonists with a low dopamine genetic risk score were over 18 times more likely to have an impulsive behavior compared to higher scores (p = 0.04). The 38% of patients taking agonists who had at least one impulsive behavior were more likely to be male and report higher Unified Parkinson's Disease Rating Scale I&II scores. With increasing time on dopamine agonists (range 92-2283 days, mean 798 ± 565 standard deviation), only patients with a high dopamine genetic risk score showed an increase in number of impulsive behaviors (p = 0.033). Predictive effects of the gene score were not present in de novo or healthy control. CONCLUSIONS: A dopamine genetic risk score can identify patients most at risk of developing impulsive behaviors on dopamine agonist medication and predict how these behaviors may worsen over time.

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

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. Deep grey matter structures play a critical role 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 behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour 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. Worse sensorimotor behaviour 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 behaviour 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 behaviour 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 behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes.