Peripheral focused ultrasound stimulation and its applications: From therapeutics to human-computer interaction.

Peripheral focused ultrasound stimulation (pFUS) has gained increasing attention in the past few decades, because it can be delivered to peripheral nerves, neural endings, or sub-organs. With different stimulation parameters, ultrasound stimulation could induce different modulation effects. Depending on the transmission medium, pFUS can be classified as body-coupled US stimulation, commonly used for therapeutics or neuromodulation, or as an air-coupled contactless US haptic system, which provides sensory inputs and allows distinct human-computer interaction paradigms. Despite growing interest in pFUS, the underlying working mechanisms remain only partially understood, and many applications are still in their infancy. This review focused on existing applications, working mechanisms, the latest progress, and future directions of pFUS. In terms of therapeutics, large-sample randomized clinical trials in humans are needed to translate these state of art techniques into treatments for specific diseases. The airborne US for human-computer interaction is still in its preliminary stage, but further efforts in task-oriented US applications might provide a promising interaction tool soon.

Can Transcranial Electrical Stimulation Facilitate Post-stroke Cognitive Rehabilitation? A Systematic Review and Meta-Analysis.

Background: Non-invasive brain stimulation methods have been widely utilized in research settings to manipulate and understand the functioning of the human brain. In the last two decades, transcranial electrical stimulation (tES) has opened new doors for treating impairments caused by various neurological disorders. However, tES studies have shown inconsistent results in post-stroke cognitive rehabilitation, and there is no consensus on the effectiveness of tES devices in improving cognitive skills after the onset of stroke. Objectives: We aim to systematically investigate the efficacy of tES in improving post-stroke global cognition, attention, working memory, executive functions, visual neglect, and verbal fluency. Furthermore, we aim to provide a pathway to an effective use of stimulation paradigms in future studies. Methods: Preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines were followed. Randomized controlled trials (RCTs) were systematically searched in four different databases, including Medline, Embase, Pubmed, and PsychInfo. Studies utilizing any tES methods published in English were considered for inclusion. Standardized mean difference (SMD) for each cognitive domain was used as the primary outcome measure. Results: The meta-analysis includes 19 studies assessing at least one of the six cognitive domains. Five RCTs studying global cognition, three assessing visual neglect, five evaluating working memory, three assessing attention, and nine studies focusing on aphasia were included for meta-analysis. As informed by the quantitative analysis of the included studies, the results favor the efficacy of tES in acute improvement in aphasic deficits (SMD = 0.34, CI = 0.02-0.67, p = 0.04) and attention deficits (SMD = 0.59, CI = -0.05-1.22, p = 0.07), however, no improvement was observed in any other cognitive domains. Conclusion: The results favor the efficacy of tES in an improvement in aphasia and attentive deficits in stroke patients in acute, subacute, and chronic stages. However, the outcome of tES cannot be generalized across cognitive domains. The difference in the stimulation montages and parameters, diverse cognitive batteries, and variable number of training sessions may have contributed to the inconsistency in the outcome. We suggest that in future studies, experimental designs should be further refined, and standardized stimulation protocols should be utilized to better understand the therapeutic effect of stimulation.

Disrupted cortico-peripheral interactions in motor disorders.

Motor disorders may arise from neurological damage or diseases at different levels of the hierarchical motor control system and side-loops. Altered cortico-peripheral interactions might be essential characteristics indicating motor dysfunctions. By integrating cortical and peripheral responses, top-down and bottom-up cortico-peripheral coupling measures could provide new insights into the motor control and recovery process. This review first discusses the neural bases of cortico-peripheral interactions, and corticomuscular coupling and corticokinematic coupling measures are addressed. Subsequently, methodological efforts are summarized to enhance the modeling reliability of neural coupling measures, both linear and nonlinear approaches are introduced. The latest progress, limitations, and future directions are discussed. Finally, we emphasize clinical applications of cortico-peripheral interactions in different motor disorders, including stroke, neurodegenerative diseases, tremor, and other motor-related disorders. The modified interaction patterns and potential changes following rehabilitation interventions are illustrated. Altered coupling strength, modified coupling directionality, and reorganized cortico-peripheral activation patterns are pivotal attributes after motor dysfunction. More robust coupling estimation methodologies and combination with other neurophysiological modalities might more efficiently shed light on motor control and recovery mechanisms. Future studies with large sample sizes might be necessary to determine the reliabilities of cortico-peripheral interaction measures in clinical practice.

Cortico-muscular interaction to monitor the effects of neuromuscular electrical stimulation pedaling training in chronic stroke.

Neuromuscular electrical stimulation (NMES) has been widely utilized in post-stroke motor restoration. However, its impact on the closed-loop sensorimotor control process remains largely unclear. This is the first study to investigate the directional changes in cortico-muscular interactions after repetitive rehabilitation training by measuring the noninvasive electroencephalogram (EEG) and electromyography (EMG) signals. In this study, 10 subjects with chronic stroke received 20 sessions of NMES-pedaling interventions, and each training session included three 10-min NMES-driven pedaling trials. In addition, pre- and post-intervention assessments of lower limb isometric contraction were conducted before and after the whole NMES-pedaling interventions. The EEG (128 channels) and EMG (3 bilateral lower limb sensors) signals were collected during the isometric contraction tasks for the paretic and non-paretic lower limbs. Both the cortico-muscular coherence (CMC) and generalized partial directed coherence (GPDC) values were analyzed between eight selected EEG channels in the central primary motor cortex and EMG channels. The results revealed significant clinical improvements. Additionally, rehabilitation training facilitated cortico-muscular interaction of the ipsilesional brain and paretic lower limbs (p = 0.004). Moreover, both the descending and ascending cortico-muscular pathways were altered after NMES-training (p = 0.001, p < 0.001). Therefore, the results implied potential applications of EEG-EMG in understanding neuromuscular changes during the post-stroke motor rehabilitation process.

Rewiring the Lesioned Brain: Electrical Stimulation for Post-Stroke Motor Restoration.

Electrical stimulation has been extensively applied in post-stroke motor restoration, but its treatment mechanisms are not fully understood. Stimulation of neuromotor control system at multiple levels manipulates the corresponding neuronal circuits and results in neuroplasticity changes of stroke survivors. This rewires the lesioned brain and advances functional improvement. This review addresses the therapeutic mechanisms of different stimulation modalities, such as noninvasive brain stimulation, peripheral electrical stimulation, and other emerging techniques. The existing applications, the latest progress, and future directions are discussed. The use of electrical stimulation to facilitate post-stroke motor recovery presents great opportunities in terms of targeted intervention and easy applicability. Further technical improvements and clinical studies are required to reveal the neuromodulatory mechanisms and to enhance rehabilitation therapy efficiency in stroke survivors and people with other movement disorders.

Pathway-specific modulatory effects of neuromuscular electrical stimulation during pedaling in chronic stroke survivors.

BACKGROUND: Neuromuscular electrical stimulation (NMES) is extensively used in stroke motor rehabilitation. How it promotes motor recovery remains only partially understood. NMES could change muscular properties, produce altered sensory inputs, and modulate fluctuations of cortical activities; but the potential contribution from cortico-muscular couplings during NMES synchronized with dynamic movement has rarely been discussed. METHOD: We investigated cortico-muscular interactions during passive, active, and NMES rhythmic pedaling in healthy subjects and chronic stroke survivors. EEG (128 channels), EMG (4 unilateral lower limb muscles) and movement parameters were measured during 3 sessions of constant-speed pedaling. Sensory-level NMES (20 mA) was applied to the muscles, and cyclic stimulation patterns were synchronized with the EMG during pedaling cycles. Adaptive mixture independent component analysis was utilized to determine the movement-related electro-cortical sources and the source dipole clusters. A directed cortico-muscular coupling analysis was conducted between representative source clusters and the EMGs using generalized partial directed coherence (GPDC). The bidirectional GPDC was compared across muscles and pedaling sessions for post-stroke and healthy subjects. RESULTS: Directed cortico-muscular coupling of NMES cycling was more similar to that of active pedaling than to that of passive pedaling for the tested muscles. For healthy subjects, sensory-level NMES could modulate GPDC of both ascending and descending pathways. Whereas for stroke survivors, NMES could modulate GPDC of only the ascending pathways. CONCLUSIONS: By clarifying how NMES influences neuromuscular control during pedaling in healthy and post-stroke subjects, our results indicate the potential limitation of sensory-level NMES in promoting sensorimotor recovery in chronic stroke survivors.

Cortico-Muscular Coherence Modulated by High-Definition Transcranial Direct Current Stimulation in People With Chronic Stroke.

High-definition transcranial direct current stimulation (HD-tDCS) is a potential neuromodulation apparatus for stroke rehabilitation. However, its modulatory effects in stroke subjects is still not well understood. In this paper, the offline modulatory effects of HD-tDCS on the ipsilesional primary motor cortex were investigated by performing wrist isometric contraction tasks before and after HD-tDCS in eleven unilateral chronic stroke subjects using a synchronized HD-tDCS and electroencephalogram/electromyography measurement system. This paper is a randomized, single blinded, and sham-controlled crossover study. Each subject randomly received three HD-tDCS (anode, cathode, and sham) with at least one-week washout period. Online feedback-guided medium-level wrist isometric contraction tasks were conducted for the affected upper limbs before stimulation and 10, 30, and 50 min after the end of 10-min 1-mA HD-tDCS. The characteristics of corticomuscular coherence (CMC), cortical oscillation power spectral density, and power spectral entropy were analyzed during tasks and compared across all sessions and stimulation conditions. Anode HD-tDCS induced significant CMC changes in stroke subjects, while cathode and sham stimulation did not induce significant CMC changes. The largest neuromodulation effects were observed at 10 min immediately after anodal HD-tDCS.

Excitation Comparison between Multi-site Stimulation using Network-based tDCS and Focal Stimulation using High-definition tDCS.

Transcranial direct current stimulation (tDCS) has been developed rapidly in recent years and derived various forms which serve as therapeutic tools for neurological disorders. However, differences of stimulation effect among these stimulation strategies have not been fully explored. In this pilot study, we compared the stimulation effect between High-definition tDCS (HD-tDCS) and Network-based tDCS (NB-tDCS) on a healthy subject. HD-tDCS mainly stimulated primary motor cortex with 2mA current and NB-tDCS was designed to stimulate main motor-related areas including primary motor cortex, premotor cortex and supplementary motor area with the same amount of current in total. Cortico-muscular coherence (CMC) derived from EEG/EMG, which measures the synchrony between cortical neural activity and muscles, was collected from isometric wrist extension tasks. The results demonstrated more motor-related regions excited and longer high-level lasting effect after NB-tDCS compared with HD-tDCS, which indicated the potential power of multi-site stimulation. This study might provide some guidance and hints for transcranial stimulation strategies in the future.

Low Gamma Band Cortico-muscular Coherence Inter-Hemisphere Difference following Chronic Stroke.

Brain oscillation and motor control process would change due to chronic stroke. Inter-hemisphere brain activation patterns may relate to motor related recovery. This study employed cortico-muscular coherence to explore cortical motor control process during wrist isometric contraction experiments of both affected and unaffected hands from chronic stroke subjects. Eleven chronic stroke subjects with moderate hand function involved in the experiments and each subject took three visits. Multitaper coherence estimation with bias-correction was performed to acquire cortico-muscular coherence, neuronal coherence source Localization was conducted to determine typical scalp motivation area during isometric contraction. Non-parametric permutation based multiple frequency bin statistics was utilized to compare the difference between two sides. The results demonstrated significant typical low gamma band inter-hemisphere disparity in cortico-muscular coherence between two sides after chronic stroke. The spatial topographical pattern and source Localization outcomes also supported these findings.