β-Oscillations Reflect Recovery of the Paretic Upper Limb in Subacute Stroke

Background. Recovery of upper limb function post-stroke can be partly predicted by initial motor function, but the mechanisms underpinning these improvements have yet to be determined. Here, we sought to identify neural correlates of post-stroke recovery using longitudinal magnetoencephalography (MEG) assessments in subacute stroke survivors. Methods. First-ever, subcortical ischemic stroke survivors with unilateral mild to moderate hand paresis were evaluated at 3, 5, and 12 weeks after stroke using a finger-lifting task in the MEG. Cortical activity patterns in the β-band (16-30 Hz) were compared with matched healthy controls. Results. All stroke survivors (n=22; 17 males) had improvements in action research arm test (ARAT) and Fugl-Meyer upper extremity (FM-UE) scores between 3 and 12 weeks. At 3 weeks post-stroke the peak amplitudes of the movement-related ipsilesional β-band event-related desynchronization (β-ERD) and synchronization (β-ERS) in primary motor cortex (M1) were significantly lower than the healthy controls (p<0.001) and were correlated with both the FM-UE and ARAT scores (r=0.51-0.69, p<0.017). The decreased β-ERS peak amplitudes were observed both in paretic and non-paretic hand movement particularly at 3 weeks post-stroke, suggesting a generalized disinhibition status. The peak amplitudes of ipsilesional β-ERS at week 3 post-stroke correlated with the FM-UE score at 12 weeks (r=0.54, p=0.03) but no longer significant when controlling for the FM-UE score at 3 weeks post-stroke. Conclusions. Although early β-band activity does not independently predict outcome at 3 months after stroke, it mirrors functional changes, giving a potential insight into the mechanisms underpinning recovery of motor function in subacute stroke.

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Brain stimulation for arm recovery after stroke (B-STARS): protocol for a randomised controlled trial in subacute stroke patients

BMJ Open ◽

10.1136/bmjopen-2017-016566 ◽

2017 ◽

Vol 7 (8) ◽

pp. e016566

Author(s):

Eline C C van Lieshout ◽

Johanna M A Visser-Meily ◽

Sebastiaan F W Neggers ◽

H Bart van der Worp ◽

Rick M Dijkhuizen

Keyword(s):

Motor Cortex ◽

Upper Limb ◽

Brain Stimulation ◽

Primary Outcome ◽

Primary Motor Cortex ◽

Repetitive Transcranial Magnetic Stimulation ◽

Stroke Patients ◽

Post Stroke ◽

Subacute Stroke

IntroductionMany patients with stroke have moderate to severe long-term sensorimotor impairments, often including inability to execute movements of the affected arm or hand. Limited recovery from stroke may be partly caused by imbalanced interaction between the cerebral hemispheres, with reduced excitability of the ipsilesional motor cortex while excitability of the contralesional motor cortex is increased. Non-invasive brain stimulation with inhibitory repetitive transcranial magnetic stimulation (rTMS) of the contralesional hemisphere may aid in relieving a post-stroke interhemispheric excitability imbalance, which could improve functional recovery. There are encouraging effects of theta burst stimulation (TBS), a form of TMS, in patients with chronic stroke, but evidence on efficacy and long-term effects on arm function of contralesional TBS in patients with subacute hemiparetic stroke is lacking.Methods and analysisIn a randomised clinical trial, we will assign 60 patients with a first-ever ischaemic stroke in the previous 7–14 days and a persistent paresis of one arm to 10 sessions of real stimulation with TBS of the contralesional primary motor cortex or to sham stimulation over a period of 2 weeks. Both types of stimulation will be followed by upper limb training. A subset of patients will undergo five MRI sessions to assess post-stroke brain reorganisation. The primary outcome measure will be the upper limb function score, assessed from grasp, grip, pinch and gross movements in the action research arm test, measured at 3 months after stroke. Patients will be blinded to treatment allocation. The primary outcome at 3 months will also be assessed in a blinded fashion.Ethics and disseminationThe study has been approved by the Medical Research Ethics Committee of the University Medical Center Utrecht, The Netherlands. The results will be disseminated through (open access) peer-reviewed publications, networks of scientists, professionals and the public, and presented at conferences.Trial registration numberNTR6133

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The Role of Continuous Theta Burst TMS in the Neurorehabilitation of Subacute Stroke Patients: A Placebo-Controlled Study

Frontiers in Neurology ◽

10.3389/fneur.2021.749798 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ana Dionísio ◽

Rita Gouveia ◽

João Castelhano ◽

Isabel Catarina Duarte ◽

Gustavo C. Santo ◽

...

Keyword(s):

Motor Function ◽

Primary Motor Cortex ◽

Phase Iii ◽

Repeated Measure ◽

Controlled Study ◽

Stroke Patients ◽

Post Stroke ◽

Subacute Stroke ◽

Theta Burst

Objectives: Transcranial magnetic stimulation, in particular continuous theta burst (cTBS), has been proposed for stroke rehabilitation, based on the concept that inhibition of the healthy hemisphere helps promote the recovery of the lesioned one. We aimed to study its effects on cortical excitability, oscillatory patterns, and motor function, the main aim being to identify potentially beneficial neurophysiological effects.Materials and Methods: We applied randomized real or placebo stimulation over the unaffected primary motor cortex of 10 subacute (7 ± 3 days) post-stroke patients. Neurophysiological measurements were performed using electroencephalography and electromyography. Motor function was assessed with the Wolf Motor Function Test. We performed a repeated measure study with the recordings taken pre-, post-cTBS, and at 3 months' follow-up.Results: We investigated changes in motor rhythms during arm elevation and thumb opposition tasks and found significant changes in beta power of the affected thumb's opposition, specifically after real cTBS. Our results are consistent with an excitatory response (increase in event-related desynchronization) in the sensorimotor cortical areas of the affected hemisphere, after stimulation. Neither peak-to-peak amplitude of motor-evoked potentials nor motor performance were significantly altered.Conclusions: Consistently with the theoretical prediction, this contralateral inhibitory stimulation paradigm changes neurophysiology, leading to a significant excitatory impact on the cortical oscillatory patterns of the contralateral hemisphere. These proof-of-concept results provide evidence for the potential role of continuous TBS in the neurorehabilitation of post-stroke patients. We suggest that these changes in ERS/ERD patterns should be further explored in future phase IIb/phase III clinical trials, in larger samples of poststroke patients.

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Functional Brain Correlates of Upper Limb Spasticity and Its Mitigation following Rehabilitation in Chronic Stroke Survivors

Stroke Research and Treatment ◽

10.1155/2014/306325 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Svetlana Pundik ◽

Adam D. Falchook ◽

Jessica McCabe ◽

Krisanne Litinas ◽

Janis J. Daly

Keyword(s):

Motor Function ◽

Upper Limb ◽

Muscle Tone ◽

Hand Movement ◽

Chronic Stroke ◽

Motor Deficits ◽

Stroke Survivors ◽

Functional Brain ◽

Brain Correlates ◽

Limb Spasticity

Background.Arm spasticity is a challenge in the care of chronic stroke survivors with motor deficits. In order to advance spasticity treatments, a better understanding of the mechanism of spasticity-related neuroplasticity is needed.Objective.To investigate brain function correlates of spasticity in chronic stroke and to identify specific regional functional brain changes related to rehabilitation-induced mitigation of spasticity.Methods.23 stroke survivors (>6 months) were treated with an arm motor learning and spasticity therapy (5 d/wk for 12 weeks). Outcome measures included Modified Ashworth scale, sensory tests, and functional magnetic resonance imaging (fMRI) for wrist and hand movement.Results.First, at baseline, greater spasticity correlated with poorer motor function (P=0.001) and greater sensory deficits (P=0.003). Second, rehabilitation produced improvement in upper limb spasticity and motor function (P<0.0001). Third, at baseline, greater spasticity correlated with higher fMRI activation in the ipsilesional thalamus (rho=0.49,P=0.03). Fourth, following rehabilitation, greater mitigation of spasticity correlated with enhanced fMRI activation in the contralesional primary motor (r=-0.755,P=0.003), premotor (r=−0.565,P=0.04), primary sensory (r=−0.614,P=0.03), and associative sensory (r=−0.597,P=0.03) regions while controlling for changes in motor function.Conclusions.Contralesional motor regions may contribute to restoring control of muscle tone in chronic stroke.

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Abstract W MP41: Potentiation of Gaba-Mediated Synaptic Inhibition in the Recovery Phase: A Novel Therapeutic Target for Stroke

Stroke ◽

10.1161/str.45.suppl_1.wmp41 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Takeshi Hiu ◽

Tonya Bliss ◽

Jeanne Paz ◽

Eric Wang ◽

Zoya Farzampour ◽

...

Keyword(s):

Pyramidal Cells ◽

Recovery Phase ◽

Synaptic Activity ◽

Stroke Recovery ◽

Functional Changes ◽

Post Stroke ◽

Array Tomography ◽

Neuronal Inhibition ◽

Gaba Signaling ◽

Novel Therapeutic

Background: Stroke is a major cause of disability yet pharmacotherapy targeting the recovery phase is lacking. Cortical circuit reorganization adjacent to the stroke site promotes recovery, thus elucidating mechanisms that promote this plasticity could lead to new therapeutics. Tonic neuronal inhibition, mediated by extrasynaptic GABA A receptors,inhibits post-stroke recovery. However, effects of phasic (synaptic) GABA signaling - which promotes plasticity during development - are unknown. Here we use a combined approach of i) array tomography to determine the composition of GABA synapses in the post-stroke mouse brain, ii) electrophysiology to determine whether stroke leads to functional changes in GABA-mediated phasic inhibition, and (iii) treatment with zolpidem, an FDA-approved GABA agonist, to modulate recovery. Results: We found, using array tomography, a 1.7-fold increase in the number of GABAergic synapses containing the α1 receptor subunit in layer 5 of the peri-infarct cortex (synapse number/μm 3 : 0.039±0.006 (control) vs 0.064±0.006 (stroke); P<0.01), but not in layer 2/3. There was an associated increase in spontaneous inhibitory post-synaptic currents (sIPSC) specific to layer 5 pyramidal neurons (sIPSC charge (fC): -403±27.8 (control) vs -724±166 (stroke); p=0.03). This effect was transient, occurring during the onset of functional recovery. To test whether the increased phasic inhibitory GABAergic signaling promotes stroke recovery, we treated animals with zolpidem, an agonist with high affinity for α1 subunit-containing GABA A receptors. Low dose zolpidem increased GABA A phasic signaling in layer 5 pyramidal cells and notably increased the rate and extent of behavioral recovery without altering infarct size. Conclusions: These data provide the first evidence that enhanced GABA A -mediated synaptic activity during the recovery phase improves stroke outcome. These data identify modulation of phasic GABA signaling as a novel therapeutic strategy for stroke, indicate zolpidem as a potential drug to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA inhibition in stroke recovery.

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