{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T17:06:08Z","timestamp":1784567168284,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Neuroscience Institute Clinician Scientist","award":["CSSDFD24apr-0002"],"award-info":[{"award-number":["CSSDFD24apr-0002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Stroke is a leading cause of neurological disability worldwide, with upper limb impairment affecting approximately 70% of survivors and only 5\u201320% achieving complete dexterity recovery at six months. Brain\u2013computer interface (BCI) neurorehabilitation decodes motor intentions from electroencephalographic (EEG) signals to deliver synchronized functional electrical stimulation (FES) and virtual reality feedback, creating a closed-loop neurofeedback system that reinforces motor learning. While existing evidence supports BCI efficacy and safety in chronic stroke, its feasibility, safety, and cost-effectiveness during the acute and subacute phase (2 to 12 weeks post-stroke), when neuroplasticity is heightened, remain underexplored. Furthermore, there is a paucity of data regarding preliminary health economic analyses for BCI rehabilitation in acute stroke rehabilitation settings. Methods: This prospective, open-label, single-arm pragmatic feasibility pilot trial will recruit 12 patients with hemorrhagic or ischemic stroke (2\u201312 weeks post-stroke) undergoing inpatient rehabilitation from a public healthcare institution. Up to 15 sessions of BCI-rehabilitation of 30 min each using the recoveriX system will be supervised by a trained therapist or clinical research assistant (4\u20135 sessions\/week over 3\u20134 weeks), followed by standard occupational therapy within 30\u201360 min of BCI-rehabilitation. Primary outcomes assessing feasibility and adherence include eligibility and recruitment rate (%\/screened); tolerability using self-rated System Usability Scale (SUS) score; within-session adherence &gt; 80%\/240 trials, summated for completed trials per patient; programme completion number &gt; 80% of scheduled (&gt;12\/15) sessions; and training-related adverse events per patient \u2264 17% (\u22642\/12 sessions). Secondary outcome measures include clinical efficacy by arm impairment scale using hemiplegic Upper Limb Fugl\u2013Meyer Motor Assessment (FMA-UE), hand function using Action Research Arm Test (ARAT), admission and discharge functional status (Functional Independence Measure-FIM (18\u2013126), Modified Barthel Index-MBI (0\u2013100), stroke impact scale (SIS_3.0), arm, participation domains), and economic analysis. All outcomes will be measured by trained therapists\/researchers at baseline week 0, week 3\u20134 (post-BCI-rehabilitation), and week 12 and 24 (follow-up). BCI-rehabilitation EEG-derived electrophysiological correlates of recovery will be extracted to better understand participant progress over time. An incremental cost-utility analysis will compare the BCI-rehabilitation participants against propensity-matched historical controls from the TTSH stroke rehabilitation registry (2017 to 2025), stratified by baseline motor severity. Discussion: This study will provide preliminary evidence on feasibility, tolerability, safety, clinical efficacy, and cost-effectiveness of early BCI-rehabilitation in acute\/subacute stroke to better inform clinicians on its implementation.<\/jats:p>","DOI":"10.3390\/jcm15145692","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:19:27Z","timestamp":1784564367000},"page":"5692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Motor Imagery Brain\u2013Computer Interface (MI-BCI)-Assisted Upper Limb Neurorehabilitation for Acute Stroke During Inpatient Rehabilitation: A Prospective Feasibility Study with Economic Evaluation Protocol"],"prefix":"10.3390","volume":"15","author":[{"given":"Ravi","family":"Shankar","sequence":"first","affiliation":[{"name":"Clinical Research & Innovation Office, Tan Tock Seng Hospital, National Healthcare Group (NHG) Health, Singapore 138543, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4234-8991","authenticated-orcid":false,"given":"Yu Tung","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Neuroscience Institute, Singapore 308433, Singapore"},{"name":"Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"Rehabilitation Research Institute of Singapore, Nanyang Technological University, Singapore 639798, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin Lay","family":"Fong","sequence":"additional","affiliation":[{"name":"National Healthcare Group (NHG) Health, Institute of Rehabilitation Excellence, Tan Tock Seng Hospital Rehabilitation Centre, Singapore 138543, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Keong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Neuroscience Institute, Singapore 308433, Singapore"},{"name":"Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9809-3425","authenticated-orcid":false,"given":"Karen Sui Geok","family":"Chua","sequence":"additional","affiliation":[{"name":"Rehabilitation Research Institute of Singapore, Nanyang Technological University, Singapore 639798, Singapore"},{"name":"National Healthcare Group (NHG) Health, Institute of Rehabilitation Excellence, Tan Tock Seng Hospital Rehabilitation Centre, Singapore 138543, Singapore"},{"name":"Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional, and national burden of stroke and its risk factors, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"20","author":"Feigin","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1161\/STROKEAHA.115.009421","article-title":"Functional and motor outcome 5 years after stroke is equivalent to outcome at 2 months: Follow-up of the collaborative evaluation of rehabilitation in stroke across Europe","volume":"46","author":"Meyer","year":"2015","journal-title":"Stroke"},{"key":"ref_3","unstructured":"National Registry of Diseases Office (2025). Singapore Stroke Registry Annual Report 2022."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Venketasubramanian, N. (2024). Stroke Demographics, Risk Factors, Subtypes, Syndromes, Mechanisms and Inter-Ethnic Differences between Chinese, Malays and Indians in Singapore\u2014A Hospital-Based Study. J. Cardiovasc. Dev. Dis., 11.","DOI":"10.3390\/jcdd11060180"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hatem, S.M., Saussez, G., Della Faille, M., Prist, V., Zhang, X., Dispa, D., and Bleyenheuft, Y. (2016). Rehabilitation of Motor Function after Stroke: A Multiple Systematic Review Focused on Techniques to Stimulate Upper Extremity Recovery. Front. Hum. Neurosci., 10.","DOI":"10.3389\/fnhum.2016.00442"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e71789","DOI":"10.2196\/71789","article-title":"Recommendations for Combining Brain-Computer Interface, Motor Imagery, and Virtual Reality in Upper Limb Stroke Rehabilitation: Qualitative Participatory Design Study","volume":"12","author":"Oliveira","year":"2025","journal-title":"JMIR Rehabil. Assist. Technol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S1474-4422(14)70160-7","article-title":"Constraint-induced movement therapy after stroke","volume":"14","author":"Kwakkel","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1177\/1545968321997769","article-title":"A Robotic System with EMG-Triggered Functional Electrical Stimulation for Restoring Arm Functions in Stroke Survivors","volume":"35","author":"Ambrosini","year":"2021","journal-title":"Neurorehabil. Neural Repair."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Li, X., He, Y., Wang, D., and Rezaei, M.J. (2024). Stroke rehabilitation: From diagnosis to therapy. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1402729"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1177\/15459683221138751","article-title":"Brain-Computer Interface-Controlled Exoskeletons in Clinical Neurorehabilitation: Ready or Not?","volume":"36","author":"Colucci","year":"2022","journal-title":"Neurorehabil. Neural Repair."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Belkacem, A.N., Jamil, N., Palmer, J.A., Ouhbi, S., and Chen, C. (2020). Brain Computer Interfaces for Improving the Quality of Life of Older Adults and Elderly Patients. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00692"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nrneurol.2016.113","article-title":"Brain-computer interfaces for communication and rehabilitation","volume":"12","author":"Chaudhary","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.1016\/j.apmr.2014.08.008","article-title":"Facilitating effects of transcranial direct current stimulation on motor imagery brain-computer interface with robotic feedback for stroke rehabilitation","volume":"96","author":"Ang","year":"2015","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1002\/ana.23879","article-title":"Brain-machine interface in chronic stroke rehabilitation: A controlled study","volume":"74","author":"Broetz","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.nicl.2017.03.005","article-title":"Plasticity of premotor cortico-muscular coherence in severely impaired stroke patients with hand paralysis","volume":"14","author":"Belardinelli","year":"2017","journal-title":"Neuroimage Clin."},{"key":"ref_16","first-page":"7084618","article-title":"Longitudinal Analysis of Stroke Patients\u2019 Brain Rhythms during an Intervention with a Brain-Computer Interface","volume":"2019","year":"2019","journal-title":"Neural Plast."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0304-3940(97)00889-6","article-title":"Motor imagery activates primary sensorimotor area in humans","volume":"239","author":"Pfurtscheller","year":"1997","journal-title":"Neurosci. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1177\/15459683211062895","article-title":"Brain-Computer Interface Training Based on Brain Activity Can Induce Motor Recovery in Patients with Stroke: A Meta-Analysis","volume":"36","author":"Nojima","year":"2022","journal-title":"Neurorehabil Neural Repair."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12984-020-00686-2","article-title":"Immediate and long-term effects of BCI-based rehabilitation of the upper extremity after stroke: A systematic review and meta-analysis","volume":"17","author":"Bai","year":"2020","journal-title":"J. Neuroeng. Rehabil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3233\/NRE-230215","article-title":"Efficacy of brain-computer interfaces on upper extremity motor function rehabilitation after stroke: A systematic review and meta-analysis","volume":"54","author":"Zhang","year":"2024","journal-title":"NeuroRehabilitation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1177\/155005941104200411","article-title":"A large clinical study on the ability of stroke patients to use an EEG-based motor imagery brain-computer interface","volume":"42","author":"Ang","year":"2011","journal-title":"Clin. EEG Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1177\/1545968312445910","article-title":"Resting state changes in functional connectivity correlate with movement recovery for BCI and robot-assisted upper-extremity training after stroke","volume":"27","author":"Guan","year":"2013","journal-title":"Neurorehabil. Neural Repair."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1177\/1550059414522229","article-title":"A Randomized Controlled Trial of EEG-Based Motor Imagery Brain-Computer Interface Robotic Rehabilitation for Stroke","volume":"46","author":"Ang","year":"2015","journal-title":"Clin. EEG Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1016\/j.apmr.2024.04.001","article-title":"Neural Interface-Based Motor Neuroprosthesis in Poststroke Upper Limb Neurorehabilitation: An Individual Patient Data Meta-analysis","volume":"105","author":"Lo","year":"2024","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liu, J., Li, Y., Zhao, D., Zhong, L., Wang, Y., Hao, M., and Ma, J. (2025). Efficacy and safety of brain-computer interface for stroke rehabilitation: An overview of systematic review. Front. Hum. Neurosci., 19.","DOI":"10.3389\/fnhum.2025.1525293"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12984-025-01588-x","article-title":"Effects of brain-computer interface based training on post-stroke upper-limb rehabilitation: A meta-analysis","volume":"22","author":"Li","year":"2025","journal-title":"J. Neuroeng. Rehabil."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"E7","DOI":"10.3171\/2025.11.FOCUS25913","article-title":"Brain-computer interfaces in poststroke rehabilitation: A meta-analysis of randomized clinical trials","volume":"60","author":"Mortezaei","year":"2026","journal-title":"Neurosurg. Focus"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sebasti\u00e1n-Romagosa, M., Cho, W., Ortner, R., Murovec, N., Von Oertzen, T., Kamada, K., Allison, B.Z., and Guger, C. (2020). Brain Computer Interface Treatment for Motor Rehabilitation of Upper Extremity of Stroke Patients-A Feasibility Study. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.591435"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Jochumsen, M., Knoche, H., Kidmose, P., Kjaer, T., and Dinesen, B. (2020). Evaluation of EEG Headset Mounting for Brain-Computer Interface-Based Stroke Rehabilitation by Patients, Therapists, and Relatives. Front. Hum. Neurosci., 14.","DOI":"10.3389\/fnhum.2020.00013"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Li, Y., Yi, R., and Hu, Z. (2026). Brain-computer interface technology for motor rehabilitation in severe stroke: A narrative review. Front. Bioeng. Biotechnol., 14.","DOI":"10.3389\/fbioe.2026.1822784"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"200","DOI":"10.7326\/0003-4819-158-3-201302050-00583","article-title":"SPIRIT 2013 statement: Defining standard protocol items for clinical trials","volume":"158","author":"Chan","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"i5239","DOI":"10.1136\/bmj.i5239","article-title":"CONSORT 2010 statement: Extension to randomised pilot and feasibility trials","volume":"355","author":"Eldridge","year":"2016","journal-title":"BMJ"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jval.2021.11.1351","article-title":"Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) Statement: Updated Reporting Guidance for Health Economic Evaluations","volume":"25","author":"Husereau","year":"2022","journal-title":"Value Health"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2340\/1650197771331","article-title":"The post-stroke hemiplegic patient. 1. a method for evaluation of physical performance","volume":"7","author":"Leyman","year":"1975","journal-title":"Scand. J. Rehabil. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/pst.185","article-title":"Sample size of 12 per group rule of thumb for a pilot study","volume":"4","author":"Julious","year":"2005","journal-title":"Pharm. Stat."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/1745-6215-15-264","article-title":"Sample size requirements to estimate key design parameters from external pilot randomised controlled trials: A simulation study","volume":"15","author":"Teare","year":"2014","journal-title":"Trials"},{"key":"ref_37","first-page":"1504","article-title":"recoveriX: A new BCI-based technology for persons with stroke","volume":"2016","author":"Irimia","year":"2016","journal-title":"Annu. Int. Conf. IEEE Eng. Med. Biol. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Guger, C., Allison, B., and Gunduz, A. (2021). Brain-Computer Interface Research: A State-of-the-Art Summary 10, Springer.","DOI":"10.1007\/978-3-030-79287-9"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/S1474-4422(08)70223-0","article-title":"Brain-computer interfaces in neurological rehabilitation","volume":"7","author":"Daly","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kong, K.H., Rosiana, A., Tham, S.L., Chai, A.L.M., and Chin, L.F. (2026). Upper extremity recovery and functional outcomes in stroke survivors after inpatient rehabilitation. Singap. Med. J., 67.","DOI":"10.4103\/singaporemedj.SMJ-2025-046"},{"key":"ref_41","unstructured":"Brooke, J. (1996). SUS\u2014A Quick and Dirty Usability Scale. Usability Evaluation in Industry, CRC Press."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1109\/MSP.2008.4408441","article-title":"Optimizing spatial filters for robust EEG single-trial analysis","volume":"25","author":"Blankertz","year":"2008","journal-title":"IEEE Signal Proc. Mag."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.tics.2022.06.003","article-title":"Mirror neurons 30 years later: Implications and applications","volume":"26","author":"Bonini","year":"2022","journal-title":"Trends Cogn. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"101817","DOI":"10.1016\/j.rehab.2024.101817","article-title":"Event-related desynchronization during action observation is an early predictor of recovery in subcortical stroke: An EEG study","volume":"67","author":"Antonioni","year":"2024","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_45","first-page":"2063","article-title":"Action observation as a tool for neurorehabilitation to moderate motor deficits and aphasia following stroke","volume":"7","author":"Ertelt","year":"2012","journal-title":"Neural Regen. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1007\/s40273-025-01519-7","article-title":"Developing an EQ-5D-5L value set for Singapore","volume":"43","author":"Luo","year":"2025","journal-title":"Pharmacoeconomics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jval.2012.10.010","article-title":"Mapping to obtain EQ-5D utility values for use in NICE health technology assessments","volume":"16","author":"Longworth","year":"2013","journal-title":"Value Health"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.apmr.2013.03.007","article-title":"Rasch analysis staging methodology to classify upper extremity movement impairment after stroke","volume":"94","author":"Woodbury","year":"2013","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.2105\/AJPH.89.9.1322","article-title":"Evaluating the public health impact of health promotion interventions: The RE-AIM framework","volume":"89","author":"Glasgow","year":"1999","journal-title":"Am. J. Public Health"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e126","DOI":"10.1017\/cts.2021.789","article-title":"Understanding and applying the RE-AIM framework: Clarifications and resources","volume":"5","author":"Holtrop","year":"2021","journal-title":"J. Clin. Transl. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate\u2014A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/14\/5692\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:26:42Z","timestamp":1784564802000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/14\/5692"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":51,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jcm15145692"],"URL":"https:\/\/doi.org\/10.3390\/jcm15145692","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]}}}