Effect of tACS on the Recovery of Motor Control of the Upper Limb and Cerebral Connectivity in Chronic Stroke Patients (tACS)

Effect of Transcranial Alternating Current Stimulation on the Recovery of Motor Control of the Upper Limb and Cerebral Connectivity in Chronic-stage Stroke Patients

This project seeks to evaluate the effect of transcranial alternating current stimulation (tACS) on the recovery of motor control of the upper limb and associated neuronal synchrony during a 14-sessions (5-week) rehabilitation program for adult patients with diagnosis of stroke at chronic stage. Specifically, the stimulation on Gamma ranges, because the evidence available so far allows us to propose that the tACS in the Gamma range (around 70 Hz) facilitates motor execution.

For this purpose, the experimental approach involves active (70 Hz in Gamma rhythm and 7 Hz, Theta rhythm) and sham tACS together with an analytical and integrated motor training with a double-blind and randomized design.

Our hypothesis is that Gamma frequency tACS restores neuronal synchrony in Beta range, which enhances the upper limb motor recovery associated with a training program.

Using specific motor control parameters, clinical scales and electroencephalography, the immediate and long-term (3 months after finished the training) behavioral and neurophysiological effect of this new neurostimulation paradigm (tACS plus training) for motor rehabilitation of stroke will be established.

Study Overview

• Status: Completed
• Conditions: Rehabilitation; Chronic Stroke
• Intervention / Treatment: Device: transcranial alternating current stimulation 70 Hz; Behavioral: Training; Device: transcranial alternating current stimulation 7 Hz; Device: transcranial alternating current stimulation Sham

Detailed Description

This project seeks to evaluate the effect of transcranial alternating current stimulation (tACS) on the recovery of motor control of the upper limb and associated neuronal synchrony during a 14 sessions (5 week) rehabilitation program for adult patients with diagnosis of stroke at chronic stage. Specifically, the stimulation on Gamma ranges, because the evidence available so far allows us to propose that the tACS in the Gamma range (around 70 Hz) facilitates motor execution. For this purpose, the experimental approach involves active (70 Hz in Gamma rhythm and 7 Hz, Theta rhythm) and sham tACS together with an analytical and integrated motor training with a double-blind and randomized design.

Our hypothesis is that Gamma frequency tACS restores neuronal synchrony in Beta range, which enhances the upper limb motor recovery associated with a training program.

The general objective is to assess the effects of a combined program of tACS and upper limb training on motor performance and brain connectivity in chronic-stage stroke patients.

The specifics objectives to accomplish this are (1) Implement a system for simultaneous measurement of motor activity and EEG under tACS, considering possible postural alterations in stroke patients. (2) Evaluate the upper limb motor control and neuronal synchrony associated with motor performance during the execution of a combined stimulation and training program. Training will include analytical and functional tasks to optimize the performance in function and activity ICF level. tACS will be applied only during analytical task. (3) Analyze the changes in motor performance and neuronal synchrony for the experimental groups.

Using specific motor control parameters (kinetic and kinematic control), clinical scales and electroencephalography, the immediate and long-term (3 months after finished the training) behavioral and neurophysiological effect of this new neurostimulation paradigm (tACS plus training) for motor rehabilitation of stroke will be established.

By means of analysis of variance, clustering comparisons and linear regressions, it will be established the effect of tACS on neuronal synchrony and the parallel motor activity, as well as their underlying relationship.

We will use the REDCap platform to register all the clinical data given by the medical record and clinical assessments.

The recruitment will be made at the Clinical Center of Metropolitan University of Educational Sciences and in the Primary Care Centers that are near to the University. The sample size is 45 chronic stage stroke survivors. The sample size calculation used the data available in the study for the difference in Fugl-Meyer score between the bihemispheric and sham transcranial Direct Current Stimulation groups after the intervention (in the study of Alisar et al, 2020), considering an effect size of 1.4, a p-value of 0.05 and a power (1- beta) of 0.9, which yielded a sample size of 12 subjects per group. Now, also considering an attrition percentage of 20% and an equivalence in the size of the 3 study groups, the final sample size is 15 people per group (45 people in total).

To answer the study hypothesis, two variables will be examined as primary results:

1. Behavioral level, it will be the score on the Fugl-Meyer scale (upper extremity section). This scale has been widely used in the field of neurorehabilitation to assess motor impairments (ICF function level).
2. Neurophysiological level, the primary outcome will be the change in spectral power in the Beta band (13-30Hz) associated with motor performance in kinetic and kinematic tasks. Signal processing will follow a cluster approach using the Fieldtrip toolbox in Matlab software (R2016B).

Both variables will be subjected to a two-factor analysis of variance (experimental group factor (3 levels, tACS-70Hz, 7Hz and simulated) and time factor (4 levels referred to the measurement times)). Depending on the result, it will apply a post-hoc test (bonferroni) to study differences between levels and interactions. The association between the variables will be inspected through regression models. The level of significance will have a p-value of 0.05. The statistical analysis will be implemented in the R language and the Rstudio software. Complementary to the primary results, and in order to broaden the description of the study phenomenon, the scores of the clinical scales already described will be analyzed, as well as kinetic (absolute force, speed of force change) and kinematic variables (direction error, maximum speed) of the analytical and combined tasks. In addition, the long-scale synchrony will be described by means of connectivity variables between the electrodes already identified (phase locking value and weighted phase lag index).

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Chile
  • Santiago, Chile, 7780450
    • Centro de Habilidades Clínicas - Universidad Metropolitana de Ciencias de la Educación

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of unilateral stroke at chronic stage (6 months or more)
• Upper Extremity -Fugl Meyer > 10
• Wrist extensors strength of the paretic limb of 2 or more in the Medical Research Council (MRC) scale
• Active shoulder movement (flexion or abduction) of 30º or more
• Be able to follow the instructions necessary to achieve the training protocol

Exclusion Criteria:

• Have a cerebellar stroke or ataxia
• Have some medical condition contraindicated for tACS (epilepsy, pacemaker, prosthesis between others)
• Have post-stroke epilepsy
• Limited passive range of motion in the elbow (less than 45º in flexo-extension plane)
• Limited passive range of motion in the wrist (less than 40º in flexo-extension plane)
• Limited passive range of motion in the shoulder (less than 70º in flexo-extension plane)
• Have another neurological condition that leads to upper extremity sequelae
• Have a normal performance in the clinical test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tACS - 70 Hz group; The group will receive the training program plus 20 minutes of tACS at 70 Hz in the C3 or C4 electrode position (depending of the hemiparetic arm) during a specific kinetic and kinematic tasks in every training session.	Device: transcranial alternating current stimulation 70 Hz; Transcranial alternating current stimulation in the head above the motor cortex area of one side of the brain, according to the hemiparesis side. Electrodes with 3.14 cm2 of stimulation area will be used, therefore, the initial current intensity will be 0.21 mA, with a current density of 0.07 mA / cm2. The current intensity will be adjusted to the tactile sensory threshold and phosphenes of each patient, with in order to reduce such sensory effects, but considering that the decrease in current will not be greater than 10% of the initial intensity, in order to obtain a comparable configuration between subjects. The frequency stimulation will be 70 Hz; Behavioral: Training; Training of the upper limb with specific kinematic and kinetic tasks plus functional training
Active Comparator: tACS - 7 Hz group; The group will receive the training program plus 20 minutes of tACS at 7 Hz in the C3 or C4 electrode position (depending of the hemiparetic arm) during a specific kinetic and kinematic tasks in every training session.	Behavioral: Training; Training of the upper limb with specific kinematic and kinetic tasks plus functional training; Device: transcranial alternating current stimulation 7 Hz; Transcranial alternating current stimulation in the head above the motor cortex area of one side of the brain, according to the hemiparesis side. Electrodes with 3.14 cm2 of stimulation area will be used, therefore, the initial current intensity will be 0.21 mA, with a current density of 0.07 mA / cm2. The current intensity will be adjusted to the tactile sensory threshold and phosphenes of each patient, with in order to reduce such sensory effects, but considering that the decrease in current will not be greater than 10% of the initial intensity, in order to obtain a comparable configuration between subjects. The frequency stimulation will be 7 Hz
Sham Comparator: tACS - sham group; The group will receive the training program plus 30 seconds of tACS at 70 Hz in the C3 or C4 electrode position (depending of the hemiparetic arm) in every training session.	Behavioral: Training; Training of the upper limb with specific kinematic and kinetic tasks plus functional training; Device: transcranial alternating current stimulation Sham; Transcranial alternating current stimulation in the head above the motor cortex area of one side of the brain, according to the hemiparesis side. Electrodes with 3.14 cm2 of stimulation area will be used, therefore, the initial current intensity will be 0.21 mA, with a current density of 0.07 mA / cm2. The current intensity will be adjusted to the tactile sensory threshold and phosphenes of each patient, with in order to reduce such sensory effects, but considering that the decrease in current will not be greater than 10% of the initial intensity, in order to obtain a comparable configuration between subjects. The stimulation will be turn on for 30 seconds (at 70 Hz)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impairment Measure pre-intervention: Upper Extremity Fugl Meyer	Scale use to assess motor impairments (ICF function level), and adequately reflects the analytical motor control of force and direction of movement. The scale has a maximum of 66 points, which indicates a normal performance. Lower scores indicate worse performance.	week 0
Change of Impairment Measure post-intervention: Upper Extremity Fugl Meyer	Scale use to assess motor impairments (ICF function level), and adequately reflects the analytical motor control of force and direction of movement. The scale has a maximum of 66 points, which indicates a normal performance. Lower scores indicate worse performance.	week 5 or 6 (end of the training program)
Change of Impairment Measure follow up: Upper Extremity Fugl Meyer	Scale use to assess motor impairments (ICF function level), and adequately reflects the analytical motor control of force and direction of movement. The scale has a maximum of 66 points, which indicates a normal performance. Lower scores indicate worse performance.	week 12
EEG spectral power in Beta band pre-intervention	Change in spectral power in the Beta band (13-30Hz) associated with motor performance in kinetic and kinematic tasks	week 0
Change in EEG spectral power in Beta band post-intervention	Change in spectral power in the Beta band (13-30Hz) associated with motor performance in kinetic and kinematic tasks	week 5 or 6 (end of the training program)
Change in EEG spectral power in Beta band follow up	Change in spectral power in the Beta band (13-30Hz) associated with motor performance in kinetic and kinematic tasks	week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activity Measure: Action Research Arm Test	Action Research Arm Test will be used to evaluate de ICF activity level. The maximum score is 57, which indicate a normal perfomance. Lower scores indicate worse performance.	week 0, week 5 or 6 (end of the training program) and week 12
Change in Activity Measure post-intervention: Action Research Arm Test	Action Research Arm Test will be used to evaluate de ICF activity level. The maximum score is 57, which indicate a normal perfomance. Lower scores indicate worse performance.	week 5 or 6 (end of the training program)
Change in Activity Measure follow up: Action Research Arm Test	Action Research Arm Test will be used to evaluate de ICF activity level. The maximum score is 57, which indicate a normal perfomance. Lower scores indicate worse performance.	week 12
Performance measure in the trained kinetic task (behavioral parameter)	The change that we observed in the kinetic task in the protocol training. This outcome is a behavioral parameter that measures the change in the task that is trained in the training protocol. It is a measure of how the participants performed the kinetic task	week 0, week 5 or 6 (end of the training program) and week 12
Change in the performance measure in the trained kinetic task post-intertenvion (behavioral parameter)	The change that we observed in the kinetic task in the protocol training. This outcome is a behavioral parameter that measures the change in the task that is trained in the training protocol. It is a measure of the change in the performance in the kinetic task at the beginning of the training protocol and at the end.	week 5 or 6 (end of the training program)
Change in the performance measure in the trained kinetic task at follow up (behavioral parameter)	The change that we observed in the kinetic task in the protocol training. This outcome is a behavioral parameter that measures the change in the task that is trained in the training protocol. It is a measure of the change in the performance in the kinetic task at the beginning of the training protocol and at the 12 week follow up.	week 12
Performance measure in trained kinematic task (behavioral parameter)	The change that we observed in the kinematic task in the protocol training. This outcome is a behavioral parameter that measures the change in the task that is trained in the training protocol. It is a measure of how the participants performed the kinematic task	week 0, week 5 or 6 (end of the training program) and week 12
Change in the performance measure in the trained kinematic task post-intervention (behavioral parameter)	The change that we observed in the kinematic task in the protocol training. This outcome is a behavioral parameter that measure the change in the task that is trained in the training protocol. It is a measure of the change in the performance in the kinematic task at the beginning of the training protocol and at the end.	week 5 or 6 (end of the training program)
Change in performance measure in the trained kinematic task at follow up (behavioral parameter)	The change that we observed in the kinematic task in the protocol training. This outcome is a behavioral parameter that measure the change in the task that is trained in the training protocol. It is a measure of the change in the performance in the kinematic task at the beginning of the training protocol and at the end.	week 12

Collaborators and Investigators

• Sponsor: Universidad Metropolitana de Ciencias de la Educacion
• Investigators: Principal Investigator: Juan J Mariman, Ph.D, Universidad Metropolitana de Ciencias de la Educacion

Publications and helpful links

General Publications

• Alisar DC, Ozen S, Sozay S. Effects of Bihemispheric Transcranial Direct Current Stimulation on Upper Extremity Function in Stroke Patients: A randomized Double-Blind Sham-Controlled Study. J Stroke Cerebrovasc Dis. 2020 Jan;29(1):104454. doi: 10.1016/j.jstrokecerebrovasdis.2019.104454. Epub 2019 Nov 4.

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2023
• Primary Completion (Actual): April 7, 2025
• Study Completion (Actual): April 7, 2025

Study Registration Dates

• First Submitted: June 12, 2023
• First Submitted That Met QC Criteria: July 12, 2023
• First Posted (Actual): July 17, 2023

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: transcranial alternating current stimulation; stroke rehabilitation; motor recovery
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: FONDECYT N° 11221226

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: For now, we have no plans of sharing individual participant data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No