White Matter Biomarkers Associated with Motor Change in Individuals with Stroke: A Continuous Theta Burst Stimulation Study.

Continuous theta burst stimulation (cTBS) is a form of noninvasive repetitive brain stimulation that, when delivered over the contralesional hemisphere, can influence the excitability of the ipsilesional hemisphere in individuals with stroke. cTBS applied prior to skilled motor practice interventions may augment motor learning; however, there is a high degree of variability in individual response to this intervention. The main objective of the present study was to assess white matter biomarkers of response to cTBS paired with skilled motor practice in individuals with chronic stroke. We tested the effects of stimulation of the contralesional hemisphere at the site of the primary motor cortex (M1c) or primary somatosensory cortex (S1c) and a third group who received sham stimulation. Within each stimulation group, individuals were categorized into responders or nonresponders based on their capacity for motor skill change. Baseline diffusion tensor imaging (DTI) indexed the underlying white matter microstructure of a previously known motor learning network, named the constrained motor connectome (CMC), as well as the corticospinal tract (CST) of lesioned and nonlesioned hemispheres. Across practice, there were no differential group effects. However, when categorized as responders vs. nonresponders using change in motor behaviour, we demonstrated a significant difference in CMC microstructural properties (as measured by fractional anisotropy (FA)) for individuals in M1c and S1c groups. There were no significant differences between responders and nonresponders in clinical baseline measures or microstructural properties (FA) in the CST. The present study identifies a white matter biomarker, which extends beyond the CST, advancing our understanding of the importance of white matter networks for motor after stroke.

An acute bout of exercise modulates both intracortical and interhemispheric excitability.

Primary motor cortex (M1) excitability is modulated following a single session of cycling exercise. Specifically, short-interval intracortical inhibition and intracortical facilitation are altered following a session of cycling, suggesting that exercise affects the excitability of varied cortical circuits. Yet we do not know whether a session of exercise also impacts the excitability of interhemispheric circuits between, and other intracortical circuits within, M1. Here we present two experiments designed to address this gap in knowledge. In experiment 1, single and paired pulse transcranial magnetic stimulation (TMS) were used to measure intracortical circuits including, short-interval intracortical facilitation (SICF) tested at 1.1, 1.5, 2.7, 3.1 and 4.5 ms interstimulus intervals (ISIs), contralateral silent period (CSP) and interhemispheric interactions by measuring transcallosal inhibition (TCI) recorded from the abductor pollicus brevis muscles. All circuits were assessed bilaterally pre and two time points post (immediately, 30 min) moderate intensity lower limb cycling. SICF was enhanced in the left hemisphere after exercise at the 1.5 ms ISI. Also, CSP was shortened and TCI decreased bilaterally after exercise. In Experiment 2, corticospinal and spinal excitability were tested before and after exercise to investigate the locus of the effects found in Experiment 1. Exercise did not impact motor-evoked potential recruitment curves, Hoffman reflex or V-wave amplitudes. These results suggest that a session of exercise decreases intracortical and interhemispheric inhibition and increases facilitation in multiple circuits within M1, without concurrently altering spinal excitability. These findings have implications for developing exercise strategies designed to potentiate M1 plasticity and skill learning in healthy and clinical populations.

The effects of five sessions of continuous theta burst stimulation over contralesional sensorimotor cortex paired with paretic skilled motor practice in people with chronic stroke.

BACKGROUND: In individuals with chronic stroke, impairment of the paretic arm may be exacerbated by increased contralesional transcallosal inhibition (TCI). Continuous theta burst stimulation (cTBS) can decrease primary motor cortex (M1) excitability and TCI. However, contralesional cTBS shows inconsistent effects after stroke. Variable effects of cTBS could stem from failure to pair stimulation with skilled motor practice or a focus of applying cTBS over M1. OBJECTIVE: Here, we investigated the effects of pairing cTBS with skilled practice on motor learning and arm function. We considered the differential effects of stimulation over two different brain regions: contralesional M1 (M1c) or contralesional primary somatosensory cortex (S1c). METHODS: 37 individuals with chronic stroke participated in five sessions of cTBS and paretic arm skilled practice of a serial targeting task (STT); participants received either cTBS over M1c or S1c or sham before STT practice. Changes in STT performance and Wolf Motor Function Test (WMFT) were assessed as primary outcomes. Assessment of bilateral corticospinal, intracortical excitability and TCI were secondary outcomes. RESULTS: cTBS over sensorimotor cortex did not improve STT performance and paretic WMFT-rate beyond sham cTBS. TCI was reduced bi-directionally following the intervention, regardless of stimulation group. In addition, we observed an association between STT performance change and paretic WMFT-rate change in the M1c stimulation group only. CONCLUSIONS: Multiple sessions of STT practice can improve paretic arm function and decrease TCI bilaterally, with no additional benefit of prior cTBS. Our results suggest that improvement in STT practice following M1c cTBS scaled with change in paretic arm function in some individuals. Our results highlight the need for a better understanding of the mechanisms of cTBS to effectively identify who may benefit from this form of brain stimulation.

Sensorimotor integration in healthy aging: Baseline differences and response to sensory training.

Sensorimotor integration is the process through which somatosensory information is incorporated to inform motor output. Given its important behavioural implications, understanding the influence of healthy aging on the underlying neurophysiology of sensorimotor integration and whether it is modifiable through intervention is important. The aims of the current work were to: 1) profile aging-related differences in sensorimotor integration, and 2) to determine if sensorimotor integration in older adults can be modulated in response to sensory training. A group of older healthy individuals and younger healthy individuals participated in two experimental sessions. First, baseline neurophysiology of sensorimotor integration was assessed. Short-latency afferent inhibition, afferent facilitation, and long-latency afferent inhibition provided nerve-based assessment of sensorimotor integration. Vibration-based measures of sensorimotor integration combined vibration of abductor pollicis brevis with single and paired-pulse transcranial magnetic stimulation techniques. In the second experimental session, a 15-min block of sensory training designed to modulate sensorimotor integration preceded the same neurophysiological assessment. Results indicate that there are aging-related differences in nerve-based measures of sensorimotor integration, specifically short- and long-latency afferent inhibition. In contrast, there are not aging-related differences when peripheral muscle belly vibration is used to probe sensorimotor integration. Following sensory training there is a reduction in the cortical response to vibration. These results suggest that there is differential aging-related modulation of sensorimotor integration, based on the type of afferent information. Additionally, sensorimotor integration is modifiable with a single session of sensory training, and this ability for neuroplastic change is retained with healthy aging.

Extraction of corticospinal tract microstructural properties in chronic stroke.

BACKGROUND: Information about the structural integrity of the corticospinal tract (CST) from diffusion-weighted imaging can improve our ability to understand motor outcomes in people with upper limb impairment after stroke, especially those with severe impairment. Yet, there is no consensus on which method of CST generation most accurately represents function and impairment in individuals with chronic stroke. NEW METHOD: The aim of the study was to compare different methods of CST reconstruction and resulting microstructural properties, as well as the relationship between these properties and motor function and impairment. Fifteen individuals with mild-moderate impairment and 15 with severe impairment who were in the chronic phase post-stroke underwent a diffusion-weighted imaging scan and motor function and impairment assessments. RESULTS: Different relationships existed between reconstruction methods, microstructural properties, and impairment and function. In severe stroke, fractional anisotropy (FA) emerged over and above apparent diffusion coefficient (ADC) and tract number to index CST integrity; FA correlated with impairment and function, whereas ADC and tract number did not correlate. No significant differences between methods or microstructural properties were found in mild-moderate stroke. COMPARISON WITH EXISTING METHODS: Our study demonstrates that CST reconstruction method influences the extraction of microstructural integrity in individuals with chronic severe stroke, with FA appearing to be the most representative method. A similar line of investigation is warranted earlier post-stroke. CONCLUSION: Differences in this data set highlight the need to establish a common methodology for CST reconstruction and analysis which may eliminate discrepancies in interpreting DWI and enhance biomarker use post-stroke for motor function.

Differentiation of motor evoked potentials elicited from multiple forearm muscles: An investigation with high-density surface electromyography.

Transcranial magnetic stimulation (TMS) is a non-invasive method to measure corticospinal excitability of the primary motor cortex. However, motor evoked potentials (MEPs) elicited by TMS in a target muscle are variable; inconsistent MEPs may be due to overlapping cortical muscle representations and/or volume conduction from neighbouring muscles. The source of variable muscle responses may not be apparent using conventional bipolar electromyography (EMG), particularly over areas with several distinct neighbouring muscles (e.g. the forearm). High-density surface EMG (HDsEMG) may provide a useful means to investigate the underlying variability in amplitude and spatial distribution of MEPs. Here, we investigated the spatial distribution of MEPs in the forearm extensors using HDsEMG. HDsEMG consisted of a 16×5 grid of surface electrodes placed on the right (dominant) dorsal forearm over the extensor carpi radialis (ECR), ulnaris (ECU) and extensor digitorum communis finger extensors (EDC). MEP amplitude and distribution were recorded from 100 to 170% of resting (RMT) and active motor threshold (AMT). The distribution of MEPs was correlated to the activity recorded during selective, isometric contractions of the ECR, ECU, middle (EDC-D3) and ring (EDC-D4) finger extensors to determine the spatial distribution of MEPs in the forearm extensors. Although ECR was the hotspot, resting MEP spatial distribution was primarily correlated to that of EDC-D4 and ECU. With background ECR activation, the spatial distribution of MEPs correlated strongly with ECR. Further, while holding a background ECR contraction, EDC-D4 and ECU MEPs increased with greater stimulation intensity. Our results suggest that HDsEMG provides a useful way to differentiate which wrist extensor muscles are activated by TMS.

Multiple measures of corticospinal excitability are associated with clinical features of multiple sclerosis.

In individuals with multiple sclerosis (MS), transcranial magnetic stimulation (TMS) may be employed to assess the integrity of corticospinal system and provides a potential surrogate biomarker of disability. The purpose of this study was to provide a comprehensive examination of the relationship between multiple measures corticospinal excitability and clinical disability in MS (expanded disability status scale (EDSS)). Bilateral corticospinal excitability was assessed using motor evoked potential (MEP) input-output (IO) curves, cortical silent period (CSP), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and transcallosal inhibition (TCI) in 26 individuals with MS and 11 healthy controls. Measures of corticospinal excitability were compared between individuals with MS and controls. We evaluated the relationship(s) between age and clinical demographics such as age at MS onset (AO), disease duration (DD) and clinical disability (EDSS) with measures of corticospinal excitability. Corticospinal excitability thresholds were higher, MEP latency and CSP onset delayed and MEP durations prolonged in individuals with MS compared to controls. Age, DD and EDSS correlated with corticospinal excitability thresholds. Also, TCI duration and the linear slope of the MEP amplitude IO curve correlated with EDSS. Hierarchical regression modeling demonstrated that combining multiple TMS-based measures of corticospinal excitability accounted for unique variance in clinical disability (EDSS) beyond that of clinical demographics (AO, DD). Our results indicate that multiple TMS-based measures of corticospinal and interhemispheric excitability provide insights into the potential neural mechanisms associated with clinical disability in MS. These findings may aid in the clinical evaluation, disease monitoring and prediction of disability in MS.