BCI-FES for Upper Limb Rehabilitation in Chronic Stroke

Stroke Clinical Trial

— BCI-FES  

Official title:

Application of Functional Electrical Stimulation Therapy Coupled to a P300-based Brain-Computer Interface for Paretic Upper Limb Rehabilitation in Chronic Stroke: A Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06409754
• Other study ID #: 24-2024
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2024
• Est. completion date: August 2025

Study information

• Verified date: May 2024
• Source: Instituto Nacional de Rehabilitacion
• Contact: Jimena Quinzaños Fresnedo, MD, PhD
• Phone: +52 5559991000
• Email: jquinzanos[@]inr.gob.mx
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this research is to evaluate the benefits of an experimental therapy for motor recovery of the arm after a stroke, which includes the application of a functional electrical stimulation therapy coupled to P-300 based Brain-Computer Interface system (BCI-FES). For this purpose, the investigators will compare two groups, the first one will receive only conventional physical and occupational therapy, while the second one will receive conventional therapy together with BCI-FES therapy.

The control and experimental group will receive 20 sessions of conventional physical and occupational therapy at a rate of five sessions per week for 4 weeks (control group double dose of conventional therapy), and the experimental group will receive 20 sessions of rehabilitation with the BCI-FES system at a rate of five sessions per week for 4 weeks. Broadly speaking, the BCI is in charge of determining the movement selected by the individual and assist the hand movement while performing functional tasks. The movements included in the sessions will be hand opening, grasping, pinching, pronation and supination, which are combined to facilitate the execution of functional movements that are performed together with the manipulation of daily used utensils. The visual, sensory and motor feedback provided by the BCI-FES system that enables the individual to replicate the afferent-efferent motor circuit, contributes to the activation and recruitment of neural pathways, which is associated with motor recovery.

It should be noted that this BCI-FES system has already been tested previously in a study with healthy individuals, and in a non-randomized pilot study that used this therapy for upper limb motor function recovery in chronic post-stroke patients.

To evaluate the results, a series of tests will be applied to assess the motor recovery, including the FMA-UE: Fugl-Meyer Assessment Scale of Upper Extremity, ARAT: Action Research Arm Test, MAS: Modified Ashworth Scale, FIM: Functional Independence Measure and MAL: Motor Activity Log. Likewise, resting state functional magnetic resonance imaging studies will be performed to evaluate the degree of functional connectivity between various brain regions of interest related to the planning and execution of movements. This will determine whether the experimental therapy with BCI-FES favors arm and hand recovery in surviving stroke individuals.

Description:

About one third of patients who suffer a stroke remain with a severe and permanent disability, secondary to motor sequelae and reduced mobility. Physical and occupational therapy represents the main rehabilitation alternative in patients with paretic upper limb, however, despite this, after six months of the event about 2/3 of the patients will still be unable to use the limb in their daily life activities.

This has led to the development of new therapeutic alternatives able to enhance the effects of conventional physical therapy. The use of brain-computer interfaces represents a paradigm in neurorehabilitation of the upper limb since it can interpret the user's intentions and allow them to interact with the environment by facilitating motion execution. Some effector devices that facilitate this movement execution have been tested, with functional electrical stimulation being one of the most used.

Therefore, the objective of this research is to evaluate the benefits of an experimental therapy for motor recovery of the arm after a stroke, which includes the application of a functional electrical stimulation therapy coupled to P-300 based Brain-Computer Interface system (BCI-FES). For this purpose, the investigators will compare two groups, the first one will receive only conventional physical and occupational therapy, while the second one will receive conventional therapy together with BCI-FES therapy.

Thirty-three subjects with paretic upper limb and history of chronic stroke will be invited to participate in the study. These will be recruited through the patient database of the neurological rehabilitation department of the National Institute of Rehabilitation Luis Guillermo Ibarra Ibarra (INRLGII), as well as directly with the physicians assigned to the neurology service who will be instructed to invite patients with chronic stroke and the inclusion criteria characteristics.

They will be randomized into two groups: the experimental group will receive P300-BCI-FES therapy together with conventional physical and occupational therapy and the control group will receive only conventional physical and occupational therapy. Randomization will be stratified taking into account mainly the following variables: baseline FMA-UE score and age.

Sociodemographic variables and relevant clinical history will be collected. In addition, a series of clinical measurements will be performed through a battery of tests that will allow to know the degree of functional level of the upper limb and self-perception regarding their ability to use it in daily activities through the following scales: FMA-UE: Fugl-Meyer Assessment Scale of Upper Extremity, ARAT: Action Research Arm Test, MAS: Modified Ashworth Scale, FIM: Functional Independence Measure, MAL: Motor Activity Log. These tests will be performed before and at the end of the intervention in both groups.

Twenty rehabilitation sessions will be performed with the P300-BCI-FES system with an approximate duration of 1 hour, at a rate of five sessions per week for 4 weeks. It was decided to provide intensive therapy, since greater effectiveness and a higher degree of recovery have been seen in stroke patients who receive intensive rehabilitation than those who do not receive intensive rehabilitation. Together, the physician and the group of researchers from the division of medical engineering will conduct the rehabilitation sessions. The medical engineering researchers will be in charge of the technical aspects of the system, both on the FES and BCI side. On the other hand, the physician will be in charge of the patient and therapy aspects, verifying that the movements are performed as naturally as possible, and continuously assessing safety and fatigue during the sessions.

The P300 BCI-FES system, to be used for the intervention, consists mainly of two medical devices and a computer running the programs that control the operation of the medical devices and the BCI. The medical equipment consists of a biomedical signal acquisition system (g.Nautilus, g.tec medical engineering GmbH, Schiedlberg, Austria), and an electrical stimulation system (Rehastim 2, Hasomed GmbH, Magdeburg, Germany). Both devices comply with the international standard for medical devices (IEC/EN 60601).

Broadly speaking, the BCI (signal acquisition system + control software) is responsible for determining the movement selected by the patient, and for sending the corresponding command to the Neuroprosthesis (stimulator + control software), which in turn sends the stimulation sequences to the corresponding electrodes, to assist the patient's movement during the practice of upper limb functional tasks.

Patients will be asked to wear comfortable clothes, washed and dry hair, without having applied any creams or gels. A wireless acquisition system will be used to record EEG signals. EEG signals will be recorded from 13 EEG channels using the extended international system 10-20 (F3, F4, Cz, C3, C4, Pz, P3 P4, PO3, PO4, PO7, PO8, Oz, common reference in the right earlobe, ground in AFz). The programmable electrical stimulator Rehastim 2 will be used for electrical stimulation. The BCI2000 software platform will be used to perform all BCI tasks: EEG signal acquisition, ERP feature extraction, signal processing and classification, and finally prediction of the user-selected target motion. Once the target motion is selected, the BCI sends the corresponding output command to the FES control block, developed in MATLAB 2017b and Simulink, which in turn activates the FES system.

To conduct the rehabilitation sessions with the P300-BCI-FES system proposed above, a modified version of the classic matrix system "P300 Donchin Speller Interface" will be used, where the letters and characters will be replaced by images of hand movements and gestures including: hand opening, grasping, pinching, pronation and supination. The BCI approach will be based on the "oddball paradigm", relying on conscious recognition by the user of the intensification (color change and increase in size) of a specific target containing a hand movement or gesture, within a sequence of other non-target random visual stimuli. This will elicit the P300 component in the event related potential.

A calibration session will be undertaken to obtain a first record of EEG signals that will be used to train a classification algorithm (stepwises method linear discrimination analysis, SWLDA), using the P3Classifier tool of the BCI2000 platform. The classifier coefficients obtained in this calibration session will be used during the BCI-FEST session to predict user-selected targets.

Moreover, the rehabilitation sessions will be divided into 4 phases. The first phase will consist of action observation and target selection; in this phase the subject will be asked to maintain their attention on a specific image for 20-30 seconds and will be asked to count the number of times the image is intensified; they will also be asked to think that it is their own hand executing the observed movement. In phase 2 they will be asked to do the same as in phase one but in addition they will be asked to try to voluntarily perform the movement exemplified on the screen. In phase three they will be asked to do the same as in the first phase, but in this phase the feedback will be provided with the FES, but they will only be asked to observe the movement passively, without making any voluntary movements. In phase 4, in addition to what will be done in phase 3, they will be asked to perform a task that involves a functional movement (with utensils used in daily activities); this way they will be instructed to synchronize their voluntary movements with those induced by the FES, thus allowing them to perform the functional task. During the intervention, possible presence of visual fatigue, decreased concentration/visual attention, muscle fatigue, pain in upper limb joints, skin irritation/redness under the electrodes will be carefully monitored.

FES calibration will be performed with four pairs of transcutaneous adhesive electrodes, which are divided into two channels, one in charge of activating the flexor muscles of the wrist and fingers and the other in charge of activating the extensor muscles of the wrist and fingers. The anatomical targets of these electrodes will be the median, ulnar and radial nerves, which innervate the flexor-extensor muscles of the wrist and fingers. Channel 1 will activate the wrist flexors flexor carpi radialis and flexor carpi ulnaris; channel 2 will activate the finger flexors palmaris longus, flexor digitorum superficialis, flexor digitorum profundus; channel 3 will activate the wrist extensors extensor carpi radialis longus, extensor carpi radialis brevis, extensor carpi ulnaris; channel 4 will activate the finger extensors extensor digitorum, extensor digiti minimi, extensor indicis, extensor pollicis brevis, extensor pollicis longus.

Conventional physical and occupational therapy will be provided over 20 sessions lasting one hour, at a rate of 5 sessions per week for 4 weeks, both in the control and experimental groups to ensure equal dosage between both groups. Patients will be asked to wear comfortable clothes and will be provided with various exercises led by a physical therapist or certified health professional, working with the proprioceptive and sensorimotor components of the affected upper limb, in muscle groups: shoulder and arm, elbow and forearm, wrist, hand and phalanges; in order to improve strength and postural control, reduce spasticity and maintain mobility ranges. Likewise, other exercises will be provided in order to improve independence in activities of daily living. This will include activities such as picking up a glass, grasping and releasing a ball, using a toothbrush, putting on a shirt/shirt, cutting a fruit/vegetable, etc.

In relation to fMRI, two evaluations will be performed to determine the changes associated with neuroplasticity, one pre-intervention and one post-intervention. For this purpose, patients will be asked to wear comfortable and loose-fitting clothing, avoiding the use of metallic components. The procedure and duration of the study, which lasts approximately 1 hour, will be explained, as well as the possible side effects that may occur during the MRI studies, which are usually mild or moderate, including: ringing in the ears, paresthesia, hyperesthesia, muscle twitching, headache, dizziness, back pain, drowsiness, irritability, anxiety, nausea and xerostomia, clarifying that the patient can interrupt the study in case of major discomfort. In addition, a physician will be present during the studies to monitor and resolve any eventualities.

Resting-state fMRI will be used for the experimental design, enabling to assess functional connectivity. Also, a laterality index (LI) will be used to assess the lateralization of cortical activity and to quantify recovery. This laterality index will be calculated based on the magnitude of the fMRI signal change in the regions of interest assessed, and is represented as: LI = ROIAff-ROIUnaff / ROIAff+ROIUnaff, where ROIAff and ROIUnaff represent the activity evidenced by fMRI in the affected and unaffected regions of interest, respectively. This calculation will yield a number between -1 and +1, with positive values indicating lateralization toward the affected hemisphere and negative values indicating lateralization toward the unaffected hemisphere. Of note, the regions of interest to be evaluated will be the primary motor area (M1) of each hemisphere, primary somatosensory area (S1), dorsal premotor cortex (PMd) and ventral premotor cortex (PMv), supplementary motor area (SMA) and pre-supplementary motor area (pre-SMA), as well as the superior parietal lobe (BA7).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 33
• Est. completion date: August 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with ischemic or hemorrhagic stroke (evidenced by CT or MRI)

• =6 months from stroke onset, chronic phase

• Unilateral lesion

• Age =18 years

• Moderate-severe hemiparesis (FMA-UE: =45)

• Full passive ranges of motion in the elbow, forearm, wrist, and hand

• Minimal cognitive level necessary to follow instructions and complete tasks

• Desire to participate in the study

Exclusion Criteria:

• Neurological disorders (Parkinson's disease, epilepsy, dementia)

• Neurological or musculoskeletal condition directly affecting the upper limb (dystonia, severe spasticity -muscle tone for elbow, wrist and fingers > 3 according to modified Ashworth scale-)

• Contraindications for fMRI (implantable devices -pacemakers-, claustrophobia)

• Cognitive deficit (MoCA test < 26 points)

• Severe aphasia

• Psychiatric disorders

• More than one stroke

Related Conditions & MeSH terms

• Muscle Weakness
• Neuronal Plasticity
• Paresis
• Stroke
• Upper Extremity Paresis

Intervention

Device:
• Functional Electrical Stimulation Therapy coupled to a P-300 based Brain-Computer Interface
The intervention involves a BCI control strategy based on a modified version of the classic P300 Donchin Speller Interface, where the matrix of letters and symbols is replaced by a set of pictures including five hand gestures and wrist orientations: hand opening, grasping, pinching, pronation, and supination. This BCI approach is based on the oddball paradigm, relying on conscious recognition by the user of the intensification of a particular target movement picture, within a sequence of other, non-target, random visual stimuli. This process should evoke the P300 component in the event related potential. The aim of the training sessions is to link an action observation/target selection task, mediated by the P300-based BCI, with the practice of a FES-assisted functional task involving the target movement picture selected. Users will be instructed to synchronize their voluntary movements with the ones induced by FES, to achieve the functional target goal.

Other:
• Conventional Physical and Occupational Therapy
Conventional physical and occupational therapy will include sessions of joint mobility, muscle strength, task-specific training, sensitivity reeducation and coordination exercises directed by an experienced professional therapist.

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra	México City	Cdmx

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Rehabilitacion

Country where clinical trial is conducted

Mexico, 

References & Publications (14)

Allison BZ, Kubler A, Jin J. 30+ years of P300 brain-computer interfaces. Psychophysiology. 2020 Jul;57(7):e13569. doi: 10.1111/psyp.13569. Epub 2020 Apr 17. — View Citation

Camacho-Zavala JK, Perez-Medina AL, Mercado-Gutierrez JA, Gutierrez MI, Gutierrez-Martinez J, Aguirre-Guemez AV, Quinzanos-Fresnedo J, Perez-Orive J. Personalized protocol and scoring scale for functional electrical stimulation of the hand: A pilot feasibility study. Technol Health Care. 2022;30(1):51-63. doi: 10.3233/THC-213016. — View Citation

Hawkinson JE, Ross AJ, Parthasarathy S, Scott DJ, Laramee EA, Posecion LJ, Rekshan WR, Sheau KE, Njaka ND, Bayley PJ, deCharms RC. Quantification of adverse events associated with functional MRI scanning and with real-time fMRI-based training. Int J Behav Med. 2012 Sep;19(3):372-81. doi: 10.1007/s12529-011-9165-6. — View Citation

Kalra J, Mittal P, Mittal N, Arora A, Tewari U, Chharia A, Upadhyay R, Kumar V, Longo L. How Visual Stimuli Evoked P300 is Transforming the Brain-Computer Interface Landscape: A PRISMA Compliant Systematic Review. IEEE Trans Neural Syst Rehabil Eng. 2023;31:1429-1439. doi: 10.1109/TNSRE.2023.3246588. — View Citation

Katan M, Luft A. Global Burden of Stroke. Semin Neurol. 2018 Apr;38(2):208-211. doi: 10.1055/s-0038-1649503. Epub 2018 May 23. — View Citation

Lebedev MA, Nicolelis MA. Brain-Machine Interfaces: From Basic Science to Neuroprostheses and Neurorehabilitation. Physiol Rev. 2017 Apr;97(2):767-837. doi: 10.1152/physrev.00027.2016. — View Citation

Leeb R, Perez-Marcos D. Brain-computer interfaces and virtual reality for neurorehabilitation. Handb Clin Neurol. 2020;168:183-197. doi: 10.1016/B978-0-444-63934-9.00014-7. — View Citation

Qu H, Zeng F, Tang Y, Shi B, Wang Z, Chen X, Wang J. The clinical effects of brain-computer interface with robot on upper-limb function for post-stroke rehabilitation: a meta-analysis and systematic review. Disabil Rehabil Assist Technol. 2024 Jan;19(1):30-41. doi: 10.1080/17483107.2022.2060354. Epub 2022 Apr 21. — View Citation

Ramirez-Nava AG, Mercado-Gutierrez JA, Quinzanos-Fresnedo J, Toledo-Peral C, Vega-Martinez G, Gutierrez MI, Pacheco-Gallegos MDR, Hernandez-Arenas C, Gutierrez-Martinez J. Functional electrical stimulation therapy controlled by a P300-based brain-computer interface, as a therapeutic alternative for upper limb motor function recovery in chronic post-stroke patients. A non-randomized pilot study. Front Neurol. 2023 Aug 17;14:1221160. doi: 10.3389/fneur.2023.1221160. eCollection 2023. — View Citation

Ramos-Murguialday A, Broetz D, Rea M, Laer L, Yilmaz O, Brasil FL, Liberati G, Curado MR, Garcia-Cossio E, Vyziotis A, Cho W, Agostini M, Soares E, Soekadar S, Caria A, Cohen LG, Birbaumer N. Brain-machine interface in chronic stroke rehabilitation: a controlled study. Ann Neurol. 2013 Jul;74(1):100-8. doi: 10.1002/ana.23879. Epub 2013 Aug 7. — View Citation

Sanders ZB, Fleming MK, Smejka T, Marzolla MC, Zich C, Rieger SW, Luhrs M, Goebel R, Sampaio-Baptista C, Johansen-Berg H. Self-modulation of motor cortex activity after stroke: a randomized controlled trial. Brain. 2022 Oct 21;145(10):3391-3404. doi: 10.1093/brain/awac239. — View Citation

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Xie YL, Yang YX, Jiang H, Duan XY, Gu LJ, Qing W, Zhang B, Wang YX. Brain-machine interface-based training for improving upper extremity function after stroke: A meta-analysis of randomized controlled trials. Front Neurosci. 2022 Aug 3;16:949575. doi: 10.3389/fnins.2022.949575. eCollection 2022. — View Citation

Yang S, Li R, Li H, Xu K, Shi Y, Wang Q, Yang T, Sun X. Exploring the Use of Brain-Computer Interfaces in Stroke Neurorehabilitation. Biomed Res Int. 2021 Jun 18;2021:9967348. doi: 10.1155/2021/9967348. eCollection 2021. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Upper limb motor recovery	Fugl-Meyer Assessment Scale of Upper Extremity (FMA-UE), Minimum Value: 0 - Maximum Value: 66, Higher Score = Better Outcome.	It will be assessed at baseline before beginning the intervention, and after the end of intervention (4 weeks later).
Secondary	Upper limb function	Action Research Arm Test (ARAT), Minimum Value: 0 - Maximum Value: 57, Higher Score = Better Outcome.	It will be assessed at baseline before beginning the intervention, and after the end of intervention (4 weeks later).
Secondary	Upper limb spasticity	Modified Ashworth Scale (MAS), Minimum Value: 0 - Maximum Value: 4, Higher Score = Worse Outcome.	It will be assessed at baseline before beginning the intervention, and after the end of intervention (4 weeks later).
Secondary	Upper limb functional independence	Functional Independence Measure (FIM), Minimum Value: 18 - Maximum Value: 126, Higher Score = Better Outcome.	It will be assessed at baseline before beginning the intervention, and after the end of intervention (4 weeks later).
Secondary	Upper limb functional independence.	Motor Activity Log (MAL-30), Minimum Value: 0 - Maximum Value: 150, Higher Score = Better Outcome.	It will be assessed at baseline before beginning the intervention, and after the end of intervention (4 weeks later).
Secondary	Functional Connectivity of the brain motor regions of interest	Measured through resting-state fMRI	It will be assessed at baseline before beginning the intervention, and after the end of intervention (4 weeks later).