A Brain Centered Neuroengineering Approach for Motor Recovery After Stroke: Combined rTMS and BCI Training

A Brain Centered Neuroengineering Approach for Motor Recovery After Stroke: Combined Repetitive Transcranial Magnetic Stimulation and Brain-Computer Interface Training

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02132520

Enrollment

Registered

2014-05-07

Start date

2014-03-31

Completion date

2017-06-30

Last updated

2019-11-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hemiparesis, Stroke

Keywords

Hemiparesis, Stroke, Rehabilitation, Transcranial Magnetic Stimulation, Repetitive, Electroencephalography, Functional Neuroimaging, Brain-Computer Interface

Brief summary

The purpose of this study is to determine whether the combination of low frequency repetitive transcranial magnetic stimulation (rTMS) and motor-imagery-based brain computer interface (BCI) training is effective for enhancing motor recovery after stroke. The PI's hypothesis is that, in comparison with traditional physical therapy alone, subjects receiving supplementary rTMS and BCI training will show greater functional improvements in hand motor ability over time as well as recovery of normal motor connectivity patterns.

Detailed description

The goal of the present study is to develop and evaluate a brain based approach to improve motor recovery after stroke, by combining rTMS and BCI training. Treatments will consist of low frequency rTMS applied to the contralesional hemisphere, followed by BCI training to encourage activity within the lesioned hemisphere. The primary objective of this study is to test the main hypothesis above in a stroke patient population. Subjects will also undergo a period of BCI only treatments after completion of the combined rTMS and BCI portion.

Interventions

DEVICErTMS

Low frequency rTMS (either real or sham) will be applied to the contralesional hemisphere at a rate of 1Hz for 10 minutes.

BEHAVIORALBCI Training

BCI training will consist of a series of EEG-based motor-imagery tasks with virtual feedback presented on a computer screen.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

* 18-70 years of age * Cortical or subcortical stroke with isolated unilateral motor paresis * At least 3 months but no greater than 12 months post stroke and in stable conditions as judged by patient's physician * Impaired hand function compared to nonparetic side but at least 10 degrees of active finger extension * Able to ambulate at least 50 feet with minimal stand-by assistance * Upper Extremity Fugl Meyer (Fugl-Meyer et al., 1975) score of greater than or equal to 20 out of 66 * Beck Depression Inventory (Beck et al., 1961) less than or equal to 19 out of 63 * Mini-mental State Examination score (Folstein et al., 1975) greater than or equal to 24 out of 30 * Must have an ipsilesional motor-evoked potential (MEP) in response to TMS * Must be stable outpatients currently undergoing rehabilitation consistent with the current standards of care * Must be able to communicate clearly in English * Must be able to provide consent in writing.

Exclusion criteria

* Personal history of epilepsy or seizures within the past 2 years * Previous surgical procedure to the spinal cord * Any MRI incompatible devices * Pregnancy * Claustrophobia * Breathing disorder * Hearing problems or ringing in the ears * Bilateral motor paresis or paralysis or those patients that would require significant medical monitoring or management beyond that of a stable outpatient * Cognitive deficits, other non-motor neurological impairment, bilateral motor paresis or paralysis or those patients that would require significant medical monitoring or management beyond that of a stable outpatient

Design outcomes

Primary

Measure	Time frame	Description
Changes in Cortical Excitability and Cortical Activation Patterns as Measured by MRI and Functional MRI	Baseline, Post-Test 1 (3 weeks), Post-Test 2 (6 weeks)	The MRI and functional MRI will evaluate the extent to which cortical areas are recruited both during rest and during movement related tasks. This is quantified by a laterality index, calculated as the ratio of activations of ipsi- and contra-lesional precentral gyri during a paretic hand tracking task. A LI of -1 corresponds to entirely contralesional activation, while a value of +1 corresponds to entirely ipsilesional activation.

Secondary

Measure	Time frame	Description
Changes in Hand Motor Function as Measured by the Box and Block Test	Baseline, Post-Test 1 (3 weeks), Post-Test 2 (6 weeks)	Performance on the box and block test with the paretic hand, quantified as the number of 2.5 cm\^3 cubes grasped, lifted, and released to transfer between compartments correctly within 60 seconds.
Changes in Paretic Hand Motor Function as Measured by the Finger Tracking Test	Baseline, Post-Test 1 (3 weeks), Post-Test 2 (6 weeks)	The finger tracking test evaluates the subject's ability to track an oscillating wave with either their paretic or non-paretic finger. Subjects wore custom electro-goniometer braces on each hand, each of which included a potentiometer signaling extension and flexion of the index finger metacarpophalangeal joint. Subjects were presented with target stimuli with a random sinusoidal waveform and were instructed to move the corresponding index finger to match the target trace as the cursor moved across the screen with constant velocity. Performance was quantified by an accuracy index, calculated using the ratio of the error to the standard deviation of the target, normalized to the range of motion for each subject.
Changes in Inter-hemispheric Inhibition	Baseline, Post-Test 1 (3 weeks), Post-Test 2 (6 weeks)	Inter-hemispheric Inhibition was evaluated using paired-pulse TMS both for the stroke hemisphere to non-stroke hemisphere direction as well as for the non-stroke hemisphere to the stroke hemisphere direction. IHI was measured by applying TMS to identified left and right motor hotspots at 1 mV threshold intensity, or 130% of the RMT if 1 mV threshold could not be identified, with single unilateral pulses and paired bilateral pulses. IHI was quantified by comparing the paired-pulse peak-to-peak motor evoked potential amplitudes to the corresponding single pulse MEP amplitudes for each direction of stimulation (ipsi- to contra-lesional and contra- to ipsi-lesional).

Other

Measure	Time frame	Description
Subject Report of Symptoms	within 12 weeks of participation	The subject report of symptoms assesses whether subject experience any adverse effects as a result of participation in the study.
Changes in the Resting Motor Threshold	Baseline, Post-Test 1 (3 weeks), Post-Test 2 (6 weeks)	The resting motor threshold is a measure of cortical excitability, and will be recorded for both the stroke and non-stroke hemispheres.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Control Subjects receiving standard-of-care physical therapy only.	0
Sham rTMS + Real BCI Training Subjects will receive sham rTMS followed by real BCI training. rTMS: Low frequency rTMS (either real or sham) will be applied to the contralesional hemisphere at a rate of 1Hz for 10 minutes. BCI Training: BCI training will consist of a series of EEG-based motor-imagery tasks with virtual feedback presented on a computer screen.	1
Real rTMS + Real BCI Training Subjects will receive real rTMS followed by real BCI training. rTMS: Low frequency rTMS (either real or sham) will be applied to the contralesional hemisphere at a rate of 1Hz for 10 minutes. BCI Training: BCI training will consist of a series of EEG-based motor-imagery tasks with virtual feedback presented on a computer screen.	2
Total	3

Baseline characteristics

Characteristic	Sham rTMS + Real BCI Training	Real rTMS + Real BCI Training	Total
Age, Continuous	37 years	64.5 years	55.3 years
Region of Enrollment United States	1 participants	2 participants	3 participants
Sex: Female, Male Female	1 Participants	1 Participants	2 Participants
Sex: Female, Male Male	0 Participants	1 Participants	1 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 0	0 / 1	0 / 2
other Total, other adverse events	0 / 0	0 / 1	0 / 2
serious Total, serious adverse events	0 / 0	0 / 1	0 / 2

Outcome results

Primary

Changes in Cortical Excitability and Cortical Activation Patterns as Measured by MRI and Functional MRI

The MRI and functional MRI will evaluate the extent to which cortical areas are recruited both during rest and during movement related tasks. This is quantified by a laterality index, calculated as the ratio of activations of ipsi- and contra-lesional precentral gyri during a paretic hand tracking task. A LI of -1 corresponds to entirely contralesional activation, while a value of +1 corresponds to entirely ipsilesional activation.