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Upregulating excitability of corticospinal pathways in stroke patients using TMS neurofeedback; A pilot study.

ABSTRACT: Upper limb weakness following a stroke affects 80% of survivors and is a key factor in preventing their return to independence. State-of-the art approaches to rehabilitation often require that the patient can generate some activity in the paretic limb, which is not possible for many patients in the early period following stroke. Approaches that enable more patients to engage with upper limb therapy earlier are urgently needed. Motor imagery has shown promise as a potential means to maintain activity in the brain's motor network, when the patient is incapable of generating functional movement. However, as imagery is a hidden mental process, it is impossible for individuals to gauge what impact this is having upon their neural activity. Here we used a novel brain-computer interface (BCI) approach allowing patients to gain an insight into the effect of motor imagery on their brain-muscle pathways, in real-time. Seven patients 2-26 weeks post stroke were provided with neurofeedback (NF) of their corticospinal excitability measured by the size of motor evoked potentials (MEP) in response to transcranial magnetic stimulation (TMS). The aim was to train patients to use motor imagery to increase the size of MEPs, using the BCI with a computer game displaying neurofeedback. Patients training finger muscles learned to elevate MEP amplitudes above their resting baseline values for the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles. By day 3 for ADM and day 4 for FDI, MEP amplitudes were sustained above baseline in all three NF blocks. Here we have described the first clinical implementation of TMS NF in a population of sub-acute stroke patients. The results show that in the context of severe upper limb paralysis, patients are capable of using neurofeedback to elevate corticospinal excitability in the affected muscles. This may provide a new training modality for early intervention following stroke.

SUBMITTER: Liang WD

PROVIDER: S-EPMC7585154 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Upregulating excitability of corticospinal pathways in stroke patients using TMS neurofeedback; A pilot study.

Liang W D WD Xu Y Y Schmidt J J Zhang L X LX Ruddy K L KL

NeuroImage. Clinical 20201013

Upper limb weakness following a stroke affects 80% of survivors and is a key factor in preventing their return to independence. State-of-the art approaches to rehabilitation often require that the patient can generate some activity in the paretic limb, which is not possible for many patients in the early period following stroke. Approaches that enable more patients to engage with upper limb therapy earlier are urgently needed. Motor imagery has shown promise as a potential means to maintain acti ...[more]

PMID: 33395961

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Project description:BackgroundRepetitive TMS is used in stroke rehabilitation with predefined passive low and high-frequency stimulation. Brain State-Dependent Stimulation (BSDS)/Activity-Dependent Stimulation (ADS) using bio-signal has been observed to strengthen synaptic connections. Without the personalization of brain-stimulation protocols, we risk a one-size-fits-all approach.MethodsWe attempted to close the ADS loop via intrinsic-proprioceptive (via exoskeleton-movement) and extrinsic-visual-feedback to the brain. We developed a patient-specific brain stimulation platform with a two-way feedback system, to synchronize single-pulse TMS with exoskeleton along with adaptive performance visual feedback, in real-time, for a focused neurorehabilitation strategy to voluntarily engage the patient in the brain stimulation process.ResultsThe novel TMS Synchronized Exoskeleton Feedback (TSEF) platform, controlled by the patient's residual Electromyogram, simultaneously triggered exoskeleton movement and single-pulse TMS, once in 10 s, implying 0.1 Hz frequency. The TSEF platform was tested for a demonstration on three patients (n = 3) with different spasticity on the Modified Ashworth Scale (MAS = 1, 1+, 2) for one session each. Three patients completed their session in their own timing; patients with (more) spasticity tend to take (more) inter-trial intervals. A proof-of-concept study on two groups-TSEF-group and a physiotherapy control-group was performed for 45 min/day for 20-sessions. Dose-matched Physiotherapy was given to control-group. Post 20 sessions, an increase in ipsilesional cortical-excitability was observed; Motor Evoked Potential increased by ~48.5 μV at a decreased Resting Motor Threshold by ~15.6%, with improvement in clinical scales relevant to the Fugl-Mayer Wrist/Hand joint (involved in training) by 2.6 units, an effect not found in control-group. This strategy could voluntarily engage the patient.ConclusionA brain stimulation platform with a real-time two-way feedback system was developed to voluntarily engage the patients during the brain stimulation process and a proof-of-concept study on three patients indicates clinical gains with increased cortical excitability, an effect not observed in the control-group; and the encouraging results nudge for further investigations on a larger cohort.

Project description:Anisotropy of descending motor pathways has repeatedly been linked to the severity of motor impairment following stroke-related damage to the corticospinal tract. Despite promising findings consistently tying anisotropy of the ipsilesional corticospinal tract to motor outcome, anisotropy is not yet utilized as a biomarker for motor recovery in clinical practice as several methodological constraints hinder a conclusive understanding of degenerative processes in the ipsilesional corticospinal tract and compensatory roles of other descending motor pathways. These constraints include estimating anisotropy in voxels with multiple fibre directions, sampling biases and confounds due to ageing-related atrophy. The present study addressed these issues by combining diffusion spectrum imaging with a novel compartmentwise analysis approach differentiating voxels with one dominant fibre direction (one-directional voxels) from voxels with multiple fibre directions. Compartmentwise anisotropy for bihemispheric corticospinal and extrapyramidal tracts was compared between 25 chronic stroke patients, 22 healthy age-matched controls, and 24 healthy young controls and its associations with motor performance of the upper and lower limbs were assessed. Our results provide direct evidence for Wallerian degeneration along the entire length of the ipsilesional corticospinal tract reflected by decreased anisotropy in descending fibres compared with age-matched controls, while ageing-related atrophy was observed more ubiquitously across compartments. Anisotropy of descending ipsilesional corticospinal tract voxels showed highly robust correlations with various aspects of upper and lower limb motor impairment, highlighting the behavioural relevance of Wallerian degeneration. Moreover, anisotropy measures of two-directional voxels within bihemispheric rubrospinal and reticulospinal tracts were linked to lower limb deficits, while anisotropy of two-directional contralesional rubrospinal voxels explained gross motor performance of the affected hand. Of note, the relevant extrapyramidal structures contained fibres crossing the midline, fibres potentially mitigating output from brain stem nuclei, and fibres transferring signals between the extrapyramidal system and the cerebellum. Thus, specific parts of extrapyramidal pathways seem to compensate for impaired gross arm and leg movements incurred through stroke-related corticospinal tract lesions, while fine motor control of the paretic hand critically relies on ipsilesional corticospinal tract integrity. Importantly, our findings suggest that the extrapyramidal system may serve as a compensatory structural reserve independent of post-stroke reorganization of extrapyramidal tracts. In summary, compartment-specific anisotropy of ipsilesional corticospinal tract and extrapyramidal tracts explained distinct aspects of motor impairment, with both systems representing different pathophysiological mechanisms contributing to motor control post-stroke. Considering both systems in concert may help to develop diffusion imaging biomarkers for specific motor functions after stroke.

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Upregulating excitability of corticospinal pathways in stroke patients using TMS neurofeedback; A pilot study.

Publications

Upregulating excitability of corticospinal pathways in stroke patients using TMS neurofeedback; A pilot study.

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