Search bioRxiv⌕ Search

Biology subjects

Boyd, L. A.

Publications and source records attributed to Boyd, L. A..

14 recordsLinked to original sources

CALM-VLM: CALIBRATION AND SELECTIVE PREDICTION IN VISION-LANGUAGE MODELS FOR RELIABLE BRAIN MRI CLASSIFICATION

AO_SCPLOWBSTRACTC_SCPLOWRecent advances in vision-language models (VLMs) have demonstrated strong multimodal capabilities for medical image analysis. However, their confidence in diagnostic predictions is often unclear, limiting adoption in clinical settings. We introduce CALM-VLM (CALibration Mechanism for Vision-Language Models), which integrates confidence calibration and selective prediction into a generative 3D VLM. To create CALM-VLM, we fine-tuned the Med3DVLM architecture for Alzheimers disease (AD) and stroke classification as initial test cases. To improve reliability, we incorporated temperature scaling on the VLMs generative outputs. The calibrated model then selectively abstained from predictions when uncertain; this also improved its diagnostic accuracy. Experiments across multi-site MRI datasets, from 10 countries worldwide, show that CALM-VLM improved confidence relative to uncalibrated VLMs. Coverage-adjusted test receiver-operator characteristic curve-area under the curve (ROC-AUC) increased by 5% to 13% for both diagnostic tasks across independent test sets. Our calibrated VLM achieved a test ROC-AUC of 0.951 for AD classification and 0.905 for stroke classification. These findings highlight the importance of calibrated, uncertainty-aware VLMs for trustworthy neuroimaging AI.

neuroscience↗

Adaptation of motor control strategies and physiological arousal during repeated blocks of split-belt walking

Physiological arousal, mediated by the autonomic nervous system (ANS), is known to co-modulate with adaptation of motor control strategies, governed by the central nervous system (CNS), in response to repeated standing perturbations. However, adaptation of the ANS physiological arousal response during repeat exposure to walking challenges remains unknown. This study examines the physiological arousal response (electrodermal activation, EDA) and motor control strategy of gait during a single session of repeated exposure to blocks of split-belt walking. Twenty young adults completed three repeated blocks (3.5 min each) of split-belt walking (2:1 speed ratio) alternating with three blocks of tied-belt walking. Step length symmetry (SLS), EDA, bilateral tibialis anterior (TA) and gastrocnemius medialis (GM) muscle activation and ground reaction forces (GRFs) were measured. For each walking block, the first (early) and last (late) 15 strides were analyzed. A linear mixed-effects model (LMM) tested the effect of repeated blocks and phases (early/late) on SLS. Statistical parametric mapping (SPM) examined patterns of within-block changes in EDA, muscle activation, and GRFs. The greatest within-block adaptation of SLS occurred during first exposure to split-belt walking (S1; p<.001). Similarly, the largest magnitude of within-block adaptation in muscle activation, GRFs, and EDA occurred during S1 (p<.05). Attenuated EDA responses together with lower magnitude of motor adaptation in subsequent split blocks 2 and 3 were observed, indicating savings across the ANS and CNS. Taken together, these findings demonstrate that the ANS-mediated physiological arousal response modulates alongside the CNS-driven locomotor adaptation to repeated exposure to blocks of split-belt walking.

neuroscience↗

Females versus males exhibit greater brain activation in sensorimotor regions during motor imagery after stroke

Motor imagery (MI; the mental rehearsal of movement) activates sensorimotor regions, providing the basis for its effectiveness as an intervention for motor recovery after stroke. Yet, the impact of biological sex on MI-related brain activation after stroke is unexplored. Here, we investigated sex-related differences in MI-related brain activation after stroke and explored associations between questionnaire-based MI ability and MI-related brain activation. Thirty-four individuals with chronic stroke performed MI of a complex, upper-limb movement using their paretic arm/hand. Brain activation was captured using functional magnetic resonance imaging (fMRI). Individual differences in MI ability were also assessed prior to the scan using an established MI questionnaire. MI-related brain activation was observed across sensorimotor regions. Yet, group-level contrasts revealed greater activation in sensorimotor regions for females vs. males, while greater activation in the cerebellar and parietal regions was noted in males vs. females. Females also recruited greater ipsilesional regions vs. males. Questionnaire-based MI ability was associated with brain activation localized to occipital regions. Our findings suggest that females and males may respond differently to MI-based tasks. Further, we did not find a relationship between questionnaire-based data and activity in sensorimotor regions. This finding suggests that multiple measures of MI may be needed to assess its impact. Overall, this work informs the use of MI after stroke.

neuroscience↗

Movement quality moderates the effect of spatially congruent cues on the stability of rhythmic bimanual finger movements.

Spatially congruent cues increase the speed of bimanual reach decisions compared to abstract symbolic cues, particularly for asymmetric reaches. Asymmetric rhythmic bimanual movements are less stable than symmetric rhythmic movements, but it is not well understood if spatially congruent cues similarly increase the stability of asymmetric rhythmic bimanual movements. To address this question, in Experiment 1, participants performed symmetric and asymmetric bimanual rhythmic finger tapping movements at different movement frequencies in time with flickering spatially congruent and abstract symbolic stimuli. As expected, symmetric movements were more stable. Spatially congruent cues similarly increased the stability of symmetric and asymmetric movements compared to abstract symbolic cues. The benefits of spatial congruence and movement symmetry were restricted to high movement frequencies (>2 hertz). To better understand if the emergence of these effects at high movement frequencies was driven by a change in movement strategy, in Experiment 2, video of the hands was concurrently recorded during task performance. Markerless motion tracking software revealed that participants switched from discontinuous to continuous movement strategies with increasing movement frequency. Since discontinuous and continuous movements are thought to be controlled by distinct neuro-cogntive systems, this might explain why the beneficial effects of spatial congruence and response symmetry emerged only at high movement frequencies. Overall, results from the current study indicate that the perceptual quality of the stimulus use to cue movement frequency can have powerful effects on the stability of rhythmic bimanual movements, but that these effects may depend on whether discontinuous or continuous movement strategies are selected.

neuroscience↗

Interhemispheric inhibition between dorsal premotor and primary motor cortices is released during preparation of unimanual but not bimanual movements.

Previous research applying transcranial magnetic stimulation during unimanual reaction time tasks indicates a transient change in the inhibitory influence of dorsal premotor cortex over contralateral primary motor cortex shortly after the presentation of an imperative stimulus. Interhemispheric inhibition from the dorsal premotor cortex to the contralateral primary motor cortex shifts depending on whether the targeted effector representation in the primary motor cortex is selected for movement. Further, the timing of changes in inhibition covaries with the selection demands of the reaction time task. Less is known about modulation of dorsal premotor to primary motor cortex interhemispheric inhibition during the preparation of bimanual movements. In this study, we used a dual coil transcranial magnetic stimulation to measure dorsal premotor to primary motor cortex interhemispheric inhibition between both hemispheres during unimanual and bimanual simple reaction time trials. Interhemispheric inhibition was measured early and late in the "pre-movement period" (defined as the period immediately after the onset of the imperative stimulus and before the beginning of voluntary muscle activity). We discovered that interhemispheric inhibition was more facilitatory early in the pre-movement period compared to late in the pre-movement period during unimanual reaction time trials. In contrast, interhemispheric inhibition was unchanged throughout the pre-movement period during symmetrical bimanual reaction time trials. These results suggest that there is greater interaction between the dorsal premotor cortex and contralateral primary motor cortex during preparation of unimanual actions compared to bimanual actions.

neuroscience↗

Data-driven biomarkers outperform theory-based biomarkers in predicting stroke motor outcomes

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have predicted motor outcomes based on the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to predict chronic motor outcomes after stroke and compares the accuracy of these predictions to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients (293 female/496 male) from the ENIGMA Stroke Recovery Working Group (age 64.9{+/-}18.0 years; time since stroke 12.2{+/-}0.2 months; normalised motor score 0.7{+/-}0.5 (range [0,1]). The out-of-sample prediction accuracy of two theory-based biomarkers was assessed: lesion load of the corticospinal tract, and lesion load of multiple descending motor tracts. These theory-based prediction accuracies were compared to the prediction accuracy from three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had better prediction accuracy - as measured by higher explained variance in chronic motor outcomes - than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R2 = 0.210, p < 0.001), performing significantly better than predictions using the theory-based biomarkers of lesion load of the corticospinal tract (R2 = 0.132, p< 0.001) and of multiple descending motor tracts (R2 = 0.180, p < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R2 =0.200, p < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R2 =0.167, p < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved prediction accuracy for theory-based and data-driven biomarkers. Finally, combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R2 = 0.241, p < 0.001. Overall, these results demonstrate that models that predict chronic motor outcomes using data-driven features, particularly when lesion data is represented in terms of structural disconnection, perform better than models that predict chronic motor outcomes using theory-based features from the motor system. However, combining both theory-based and data-driven models provides the best predictions.

neuroscience↗

Females exhibit smaller and less variable patterns of brain activation across a range of motor tasks

Past work has shown that brain structure and function differ between females and males. Males have larger cortical and sub-cortical volume and surface area (both total and subregional), while females have greater cortical thickness in most brain regions. Functional differences are also reported in the literature, yet to date little work has systematically considered whether patterns of brain activity indexed with functional magnetic resonance imaging (fMRI) differ between females and males. Recently, an attempt to modernize and improve our understanding of the homunculus, a somatotopic representation of the human body within the brain, was made. Still, in the decades since it was introduced, no research has considered sex differences in the somatotopic representation. The current study sought to remediate this issue by employing brain somatotopic motor mapping from a previously published and openly available dataset. We tested differences in patterns of functional brain activity associated with 12 voluntary movement patterns in females versus males. Results suggest that females exhibited smaller volumes of brain activation across all 12 movement tasks, and lower patterns of variability in 10 of the 12 movements. We also observed that females had greater cortical thickness, which is in alignment with previous analyses of structural differences. Overall, these findings provide a basis for considering biological sex in future fMRI research and provide a foundation of understanding differences in how neurological pathologies present in females vs males.

neuroscience↗

Improved cognitive-motor processing speed and decreased functional connectivity after high intensity aerobic exercise in individuals with chronic stroke

After stroke, impaired motor performance is linked to an increased demand for cognitive resources. Aerobic exercise improves cognitive function in healthy populations and may be effective in altering cognitive function post-stroke. We sought to determine if high intensity aerobic exercise paired with motor training in individuals with chronic stroke alters cognitive-motor function and functional connectivity between the dorsolateral prefrontal cortex (DLPFC), a key region for cognitive-motor processes, and the sensorimotor network. Twenty-five participants with chronic stroke were randomly assigned to exercise (n = 14; 66 {+/-} 11 years; 4 females), or control (n = 11; 68 {+/-} 8 years; 2 females) groups. Both groups performed five-days of paretic upper limb motor training after either high intensity aerobic exercise (3 intervals of 3 minutes each, total exercise duration of 23-minutes) or watching a documentary (control). Resting-state fMRI, and TMT-A and B were recorded pre- and post-intervention. Both groups showed implicit motor sequence learning (p < .001), but there was no added benefit of exercise (p = .738). Regardless of group, the changes in task score (p = .025), and dwell time (p = .043) were correlated with a decrease in DLPFC-sensorimotor network functional connectivity (p = .024), which is thought to reflect a reduction in the cognitive demand and increased automaticity. The exercise group experienced greater overall cognitive-motor improvements measured with the trail making test part A (TMT-A: task score: p = .012; dwell time: p = .024; movement time: p = .567). Aerobic exercise may improve cognitive-motor processing speed post-stroke. Significance statementAfter stroke, impaired motor performance is linked to an increased demand for cognitive resources. In our work we show that high intensity aerobic exercise paired with an implicit motor learning task improves cognitive-motor processing speed and reduces resting-state functional connectivity between the dorsolateral prefrontal cortex and the sensorimotor network in individuals living with chronic stroke. These data likely reflect a reduction in cognitive resource dependence during a cognitive-motor task after stroke and a shift towards cognitive-motor automaticity.

neuroscience↗

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 ([&ge;]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.

neuroscience↗

Experience-dependent learning and myelin plasticity in individuals with stroke

BackgroundInjury to brain myelin disrupts motor performance and learning, however it is not clear if myelination is modulated by skilled motor practice or by recovery after stroke. Multi-component relaxation imaging can be used to measure water trapped between myelin bilayers which is expressed as myelin water fraction. The purpose of this study was to examine the effect of experience-dependent learning on myelin plasticity using multi-component relaxation imaging in individuals with stroke. MethodsThirty-two individuals with chronic stroke (>6 months) and twenty-seven healthy controls completed 4 weeks of skilled motor practice using a complex, gamified reaching task. Multi-component relaxation imaging-derived myelin water fraction was obtained before and after training. Seven brain regions associated with motor learning and sensorimotor function were investigated. ResultsAll participants improved task-specific reaching movements after training. In individuals with stroke: 1) pre-training myelin water fraction was lower in motor brain regions but higher in the cingulum compared to controls, 2) pre-training myelin water fraction in motor and sensorimotor regions was positively associated with learning rate, and 3) myelin water fraction was increased in the ipsilesional (contralateral to the trained arm) superior longitudinal fasciculus following skilled motor practice. ConclusionsFindings indicate that after stroke, myelin water fraction is related to measures of motor learning and modulated by 4 weeks of skilled motor practice with the paretic limb. Myelin water fraction can be enhanced in the chronic stage of stroke and may be an important target for upper-limb motor recovery.

neuroscience↗

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.

neuroscience↗

Multiple bouts of high-intensity interval exercise reverse age-related functional connectivity disruptions without affecting motor learning in older adults

Exercise has emerged as an intervention that may mitigate age-related resting state functional connectivity and sensorimotor declines. Here, 42 healthy older adults rested or completed 3 sets of high-intensity interval exercise for a total of 23 minutes, then immediately practiced an implicit motor task with their non-dominant hand across five separate sessions. Participants completed resting stage functional MRI before the first and after the fifth day of practice; they also returned 24-hours and 35-days later to complete short- and long-term retention. Independent component analysis of resting state functional MRI revealed increased connectivity in the frontoparietal, the dorsal attentional, and cerebellar networks and group. seed-based analysis showed strengthened connectivity between the limbic system and right cerebellum, and between the right cerebellum and bilateral middle temporal gyri in the exercise group. There was no motor learning advantage for the exercise group. Our data suggest that exercise paired with an implicit motor learning task in older adults can augment resting state functional connectivity without enhancing behaviour beyond that stimulated by skilled motor practice. Impact statementFive separate bouts of exercise paired with skilled motor practice strengthens resting state networks in brain regions that are susceptible to declines in older adults without affecting motor acquisition or learning.

neuroscience↗

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 ([&le;]90 days) and chronic ([&ge;]180 days) stroke subgroups separately, with exploratory analyses in early stroke ([&le;]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.

neuroscience↗

Reward and automatic processes in exercise behavior: A new approach and a systematic review

BackgroundIn a time of physical inactivity pandemic, attempts to better understand the factors underlying the regulation of exercise behavior is important. The dominant neuropsychological approach to exercise behavior explains physical activity as a reward. However, the opposite of physical exertion -- behaviors minimizing energy cost -- may also be a reward, which activates automatic reactions favoring the engagement in behaviors associated with lower energetic costs.\n\nObjectiveOur objective was to systematically review studies testing the automatic reactions triggered by stimuli associated with different types of exercise behavior (e.g., physical activity, sedentary behaviors) and energetic cost variations (e.g., behaviors minimizing energetic cost).\n\nMethodsTwo authors systematically searched, screened, extracted, and analyzed data from articles in the MEDLINE database.\n\nResultsWe included 26 studies. Three types of automatic processes were tested: Affective reactions, attentional capture, and approach tendencies. Results show that automatic reactions toward stimuli depicting exercise behaviors explained individuals level of physical activity. Brain imaging results show that stimuli associated with exercise behavior activate regions associated with reward, but these studies were scarce.\n\nConclusionReward is an important factor of exercise behavior. There is strong evidence showing that physical activity is a reward. While brain imaging results suggest that sedentary behaviors are also a reward, behaviors minimizing energetic cost have not been investigated so far. Additional studies are required to establish a strong and complete framework of reward in exercise behavior.\n\nKey points- Behavioral and brain imaging studies using different types of automatic behavior show that physical activity is a reward\n- Behaviors minimizing energetic cost have been essential to evolutionary survival and are likely to be a reward. However, experimental evidence remains scarce\n- The dominant neuropsychological approaches to exercise behavior may be incomplete, which may partly explain our current inability to counteract the pandemic of physical inactivity

neuroscience↗