Plasticity In Stroke Patients Research Articles

Motor imagery-based brain–computer interface rehabilitation programs enhance upper extremity performance and cortical activation in stroke patients

BackgroundThe most challenging aspect of rehabilitation is the repurposing of residual functional plasticity in stroke patients. To achieve this, numerous plasticity-based clinical rehabilitation programs have been developed. This study aimed to investigate the effects of motor imagery (MI)-based brain–computer interface (BCI) rehabilitation programs on upper extremity hand function in patients with chronic hemiplegia.DesignA 2010 Consolidated Standards for Test Reports (CONSORT)-compliant randomized controlled trial.MethodsForty-six eligible stroke patients with upper limb motor dysfunction participated in the study, six of whom dropped out. The patients were randomly divided into a BCI group and a control group. The BCI group received BCI therapy and conventional rehabilitation therapy, while the control group received conventional rehabilitation only. The Fugl–Meyer Assessment of the Upper Extremity (FMA-UE) score was used as the primary outcome to evaluate upper extremity motor function. Additionally, functional magnetic resonance imaging (fMRI) scans were performed on all patients before and after treatment, in both the resting and task states. We measured the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), z conversion of ALFF (zALFF), and z conversion of ReHo (ReHo) in the resting state. The task state was divided into four tasks: left-hand grasping, right-hand grasping, imagining left-hand grasping, and imagining right-hand grasping. Finally, meaningful differences were assessed using correlation analysis of the clinical assessments and functional measures.ResultsA total of 40 patients completed the study, 20 in the BCI group and 20 in the control group. Task-related blood-oxygen-level-dependent (BOLD) analysis showed that when performing the motor grasping task with the affected hand, the BCI group exhibited significant activation in the ipsilateral middle cingulate gyrus, precuneus, inferior parietal gyrus, postcentral gyrus, middle frontal gyrus, superior temporal gyrus, and contralateral middle cingulate gyrus. When imagining a grasping task with the affected hand, the BCI group exhibited greater activation in the ipsilateral superior frontal gyrus (medial) and middle frontal gyrus after treatment. However, the activation of the contralateral superior frontal gyrus decreased in the BCI group relative to the control group. Resting-state fMRI revealed increased zALFF in multiple cerebral regions, including the contralateral precentral gyrus and calcarine and the ipsilateral middle occipital gyrus and cuneus, and decreased zALFF in the ipsilateral superior temporal gyrus in the BCI group relative to the control group. Increased zReHo in the ipsilateral cuneus and contralateral calcarine and decreased zReHo in the contralateral middle temporal gyrus, temporal pole, and superior temporal gyrus were observed post-intervention. According to the subsequent correlation analysis, the increase in the FMA-UE score showed a positive correlation with the mean zALFF of the contralateral precentral gyrus (r = 0.425, P < 0.05), the mean zReHo of the right cuneus (r = 0.399, P < 0.05).ConclusionIn conclusion, BCI therapy is effective and safe for arm rehabilitation after severe poststroke hemiparesis. The correlation of the zALFF of the contralateral precentral gyrus and the zReHo of the ipsilateral cuneus with motor improvements suggested that these values can be used as prognostic measures for BCI-based stroke rehabilitation. We found that motor function was related to visual and spatial processing, suggesting potential avenues for refining treatment strategies for stroke patients.Trial registration: The trial is registered in the Chinese Clinical Trial Registry (number ChiCTR2000034848, registered July 21, 2020).

Lesion-specific cortical activation following sensory stimulation in patients with subacute stroke

BackgroundSensory stimulation can play a fundamental role in the activation of the primary sensorimotor cortex (S1-M1), which can promote motor learning and M1 plasticity in stroke patients. However, studies have focused mainly on investigating the influence of brain lesion profiles on the activation patterns of S1-M1 during motor tasks instead of sensory tasks. Therefore, the objective of this study is to explore the lesion-specific activation patterns due to different brain lesion profiles and types during focal vibration (FV).MethodsIn total 52 subacute stroke patients were recruited in this clinical experiment, including patients with basal ganglia hemorrhage/ischemia, brainstem ischemia, other subcortical ischemia, cortical ischemia, and mixed cortical–subcortical ischemia. Electroencephalograms (EEG) were recorded following a resting state lasting for 4 min and three sessions of FV. FV was applied over the muscle belly of the affected limb’s biceps for 3 min each session. Beta motor-related EEG power desynchronization overlying S1-M1 was used to indicate the activation of S1-M1, while the laterality coefficient (LC) of the activation of S1-M1 was used to assess the interhemispheric asymmetry of brain activation.Results(1) Regarding brain lesion profiles, FV could lead to the significant activation of bilateral S1-M1 in patients with basal ganglia ischemia and other subcortical ischemia. The activation of ipsilesional S1-M1 in patients with brainstem ischemia was higher than that in patients with cortical ischemia. No activation of S1-M1 was observed in patients with lesions involving cortical regions. (2) Regarding brain lesion types, FV could induce the activation of bilateral S1-M1 in patients with basal ganglia hemorrhage, which was significantly higher than that in patients with basal ganglia ischemia. Additionally, LC showed no significant correlation with the modified Barthel index (MBI) in all patients, but a positive correlation with MBI in patients with basal ganglia lesions.ConclusionsThese results reveal that sensory stimulation can induce lesion-specific activation patterns of S1-M1. This indicates FV could be applied in a personalized manner based on the lesion-specific activation of S1-M1 in stroke patients with different lesion profiles and types. Our study may contribute to a better understanding of the underlying mechanisms of cortical reorganization.

Associative cued asynchronous BCI induces cortical plasticity in stroke patients.

ObjectiveWe propose a novel cue‐based asynchronous brain–computer interface(BCI) for neuromodulation via the pairing of endogenous motor cortical activity with the activation of somatosensory pathways.MethodsThe proposed BCI detects the intention to move from single‐trial EEG signals in real time, but, contrary to classic asynchronous‐BCI systems, the detection occurs only during time intervals when the patient is cued to move. This cue‐based asynchronous‐BCI was compared with two traditional BCI modes (asynchronous‐BCI and offline synchronous‐BCI) and a control intervention in chronic stroke patients. The patients performed ankle dorsiflexion movements of the paretic limb in each intervention while their brain signals were recorded. BCI interventions decoded the movement attempt and activated afferent pathways via electrical stimulation. Corticomotor excitability was assessed using motor‐evoked potentials in the tibialis‐anterior muscle induced by transcranial magnetic stimulation before, immediately after, and 30 min after the intervention.ResultsThe proposed cue‐based asynchronous‐BCI had significantly fewer false positives/min and false positives/true positives (%) as compared to the previously developed asynchronous‐BCI. Linear‐mixed‐models showed that motor‐evoked potential amplitudes increased following all BCI modes immediately after the intervention compared to the control condition (p <0.05). The proposed cue‐based asynchronous‐BCI resulted in the largest relative increase in peak‐to‐peak motor‐evoked potential amplitudes(141% ± 33%) among all interventions and sustained it for 30 min(111% ± 33%).InterpretationThese findings prove the high performance of a newly proposed cue‐based asynchronous‐BCI intervention. In this paradigm, individuals receive precise instructions (cue) to promote engagement, while the timing of brain activity is accurately detected to establish a precise association with the delivery of sensory input for plasticity induction.

Imaging brain plasticity in stroke patients with simultaneous paired associative stimulation PAS /fMRI

Imaging brain plasticity in stroke patients with simultaneous paired associative stimulation PAS /fMRI

Tactile Stimulation Improves Sensorimotor Rhythm-based BCI Performance in Stroke Patients.

BCI decoding accuracy plays a crucial role in practical applications. With accurate feedback, BCI-based therapy determines beneficial neural plasticity in stroke patients. In this study, we aimed at improving sensorimotor rhythm (SMR)-based BCI performance by integrating motor tasks with tactile stimulation. Eleven stroke patients were recruited for three experimental conditions, i.e., motor attempt (MA) condition, tactile stimulation (TS) condition, and tactile stimulation-assisted motor attempt (TS-MA) condition. Tactile stimulation was delivered to the paretic hand wrist during both task and idle states using a DC vibrator. We observed that the TS-MA condition achieved greater motor-related cortical activation (MRCA) in alpha-beta band when compared with both TS and MA conditions. Consequently, online BCI decoding accuracies between task and idle states were significantly improved from 74.5% in the MA condition to 85.1% in the TS-MA condition (p < 0.001), whereas the accuracy in the TS condition was 54.6% (approaching to the chance level of 50%). This finding demonstrates that sensory afferent from peripheral nerves benefits the neural process of sensorimotor cortex in stroke patients. With appropriate sensory stimulation, MRCA is enhanced and corresponding brain patterns are more discriminative. This novel SMR-BCI paradigm shows great promise to facilitate the practical application of BCI-based stroke rehabilitation.

Electroencephalographic markers of robot-aided therapy in stroke patients for the evaluation of upper limb rehabilitation.

Stroke is the leading cause of permanent disability in developed countries; its effects may include sensory, motor, and cognitive impairment as well as a reduced ability to perform self-care and participate in social and community activities. A number of studies have shown that the use of robotic systems in upper limb motor rehabilitation programs provides safe and intensive treatment to patients with motor impairments because of a neurological injury. Furthermore, robot-aided therapy was shown to be well accepted and tolerated by all patients; however, it is not known whether a specific robot-aided rehabilitation can induce beneficial cortical plasticity in stroke patients. Here, we present a procedure to study neural underpinning of robot-aided upper limb rehabilitation in stroke patients. Neurophysiological recordings use the following: (a) 10-20 system electroencephalographic (EEG) electrode montage; (b) bipolar vertical and horizontal electrooculographies; and (c) bipolar electromyography from the operating upper limb. Behavior monitoring includes the following: (a) clinical data and (b) kinematic and dynamic of the operant upper limb movements. Experimental conditions include the following: (a) resting state eyes closed and eyes open, and (b) robotic rehabilitation task (maximum 80 s each block to reach 4-min EEG data; interblock pause of 1 min). The data collection is performed before and after a program of 30 daily rehabilitation sessions. EEG markers include the following: (a) EEG power density in the eyes-closed condition; (b) reactivity of EEG power density to eyes opening; and (c) reactivity of EEG power density to robotic rehabilitation task. The above procedure was tested on a subacute patient (29 poststroke days) and on a chronic patient (21 poststroke months). After the rehabilitation program, we observed (a) improved clinical condition; (b) improved performance during the robotic task; (c) reduced delta rhythms (1-4 Hz) and increased alpha rhythms (8-12 Hz) during the resting state eyes-closed condition; (d) increased alpha desynchronization to eyes opening; and (e) decreased alpha desynchronization during the robotic rehabilitation task. We conclude that the present procedure is suitable for evaluation of the neural underpinning of robot-aided upper limb rehabilitation.

Enhanced interhemispheric functional connectivity compensates for anatomical connection damages in subcortical stroke.

Motor recovery after stroke has been shown to be correlated with both the fractional anisotropy (FA) of the affected corticospinal tract (CST) and the interhemispheric resting-state functional connectivity (rsFC) of the primary motor cortex (M1). However, the role of the restoration or enhancement of the M1-M1 rsFC in motor recovery remains largely unknown. We aimed to clarify this issue by investigating the correlations between the M1-M1 rsFC and the integrity of the M1-M1 anatomic connection and the affected CST in chronic subcortical stroke patients with good motor outcomes. Twenty patients and 16 healthy controls underwent multimodal magnetic resonance imaging examinations. Diffusion tensor imaging was used to reconstruct the M1-M1 anatomic connection and bilateral CSTs. White matter integrity of these tracts was assessed using FA. Resting-state functional magnetic resonance imaging was used to calculate M1-M1 rsFC. Group differences in these measures were compared. Correlations between M1-M1 rsFC and FA of the M1-M1 anatomic connection and the affected CST were analyzed in patients with stroke. Compared with healthy controls, patients with stroke exhibited significantly reduced FA in the affected CST and the M1-M1 anatomic connection and a significantly increased M1-M1 rsFC. The FA values of the affected CST were positively correlated with the M1-M1 anatomic connection, and these FA values were negatively correlated with the M1-M1 rsFC in these patients. Our findings suggest that the M1-M1 anatomic connection impairment is secondary to CST damage, and the M1-M1 rsFC enhancement may reflect compensatory or reactive neural plasticity in stroke patients with CST impairment.

Clinical evidences of brain plasticity in stroke patients

Emerging findings deriving from neuromodulation and neuroradiology are providing us new insights about plas- ticity and functional reorganization of the brain after stroke, but the direct clinical assessment of motor function should still be considered an indispensable tool for the evaluation of the effects of plasticity in stroke patients. Recovery of motor function can be spontaneous or guided by training. Substantial functional recovery can occur spontaneously especially in the first month post-stroke. Instead, the guided recovery may take more time and may rely on a number of rehabilitation techniques which proved to be capable of stimulating cerebral plasticity. Even the time course of these processes is a decisive element. First, it is important to correlate the trends of plasticity after stroke, from the enhancement of earlier periods to the later stages, to the behavioral changes observed. Furthermore, it is crucial to distinguish recovery of function occurring through improvement of motor deficit from compensatory mechanisms, distinction that has also an effect on timing of recovery. Another relevant question is the maintenance over time of the improvements reached with the treatment, feature on which various clinical studies have been conducted in acute and chronic stroke patients. Further studies are needed to allow us to get a more precise definition of the potentiality of functional recovery and of the mechanisms underlying the recovery depending on its levels and timing. Understanding the mechanisms, the effects and the limits of neural plasticity may eventually help enhancing the recovery process in stroke patients, significantly improving the quality of life of these patients. Then, a greater attention towards the clinical implica- tions of the changes related to plasticity can be a crucial element to further improve the therapeutic options used in neurorehabilitation.

Central effects of botulinum neurotoxin A: Spinal plasticity in stroke patients after injection in ankle plantarflexors

Central effects of botulinum neurotoxin A: Spinal plasticity in stroke patients after injection in ankle plantarflexors

Spinal plasticity in stroke patients after botulinum neurotoxin A injection in ankle plantar flexors

The effect of botulinum neurotoxin A (BoNT-A) in stroke patients' upper limbs has been attributed to its peripheral action only. However, BoNT-A depressed recurrent inhibition of lumbar motoneurons, likely due to its retrograde transportation along motor axons affecting synapses to Renshaw cells. Because Renshaw cells control group Ia interneurons mediating reciprocal inhibition between antagonists, we tested whether this inhibition, particularly affected after stroke, could recover after BoNT-A. The effect of posterior tibial nerve (PTN) stimulation on tibialis anterior (TA) electromyogram (EMG) was investigated in 13 stroke patients during treadmill walking before and 1 month after BoNT-A injection in ankle plantar flexors. Before BoNT-A, PTN stimuli enhanced TA EMG all during the swing phase. After BoNT-A, the PTN-induced reciprocal facilitation in TA motoneurons was depressed at the beginning of swing and reversed into inhibition in midswing, but at the end of swing, the reciprocal facilitation was enhanced. This suggests that BoNT-A induced spinal plasticity leading to the recovery of reciprocal inhibition likely due to the withdrawal of inhibitory control from Renshaw cells directly blocked by the toxin. At the end of swing, the enhanced reciprocal facilitation might be due to BoNT-induced modification of peripheral afferent inputs. Therefore, both central and peripheral actions of BoNT-A can modify muscle synergies during walking: (1) limiting ankle muscle co-contraction in the transition phase from stance to swing, to assist dorsiflexion, and (2) favoring it from swing to stance, which blocks the ankle joint and thus assists the balance during the single support phase on the paretic limb.

Modulating cortical excitability in acute stroke: A repetitive TMS study

ObjectiveChanges in cerebral cortex excitability have been demonstrated after a stroke and are considered relevant for recovery. Repetitive transcranial magnetic stimulation (rTMS) of the brain can modulate cerebral cortex excitability and, when rTMS is given as theta burst stimulation (TBS), LTP- or LTD-like changes can be induced. The aim of present study was to evaluate the effects of TBS on cortical excitability in acute stroke. MethodsIn 12 acute stroke patients, we explored the effects of facilitatory TBS of the affected hemisphere and of inhibitory TBS of the unaffected hemisphere on cortical excitability to single-pulse transcranial magnetic stimulation (TMS) on both sides. The effects produced by TBS in patients were compared with those observed in a control group of age-matched healthy individuals. ResultsIn patients, both the facilitatory TBS of the affected motor cortex and the inhibitory TBS of the unaffected motor cortex produced a significant increase of the amplitude of MEPs evoked by stimulation of the affected hemisphere. The effects observed in patients were comparable to those observed in controls. ConclusionsFacilitatory TBS over the stroke hemisphere and inhibitory TBS over the intact hemisphere in acute phase enhance the excitability of the lesioned motor cortex. SignificanceTBS might be useful to promote cortical plasticity in stroke patients.

Effects of Somatosensory Stimulation on Use-Dependent Plasticity in Chronic Stroke

There is a need to develop strategies to enhance the beneficial effects of motor training, including use-dependent plasticity (UDP), in neurorehabilitation. Peripheral nerve stimulation (PNS) modulates motor cortical excitability in healthy humans and could influence training effects in stroke patients. We compared the ability of PNS applied to the (1) arm, (2) leg, and (3) idle time to influence training effects in the paretic hand in 7 chronic stroke patients. The end point measure was the magnitude of UDP. UDP was more prominent with arm stimulation (increased by 22.8%) than with idle time (by 2.9%) or leg stimulation (by 6.4%). PNS applied to the paretic limb paired with motor training enhances training effects on cortical plasticity in stroke patients.