- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT07438808
Influence of Physical Exercise on Neuroplasticity and Sensorimotor Networks in Older Adults (EXOPLASTIC)
The purpose of this study is to investigate the influence of a single session of moderate aerobic exercise on motor cortex neuroplasticity in older adults, both alone and in combination with transcranial direct current stimulation (tDCS), and to compare these effects with those observed in young adults.
Normal aging is associated with changes in the central nervous system that can affect motor function, sensorimotor integration, and cortical inhibitory mechanisms. These alterations may reduce the brain's capacity for neuroplasticity, which is essential for motor learning and functional adaptation. Physical exercise has been proposed as a potential strategy to counteract age-related decline in neuroplasticity.
In this study, healthy young and older adults will participate in three experimental sessions. Participants will complete two experimental conditions in a randomized crossover design: (1) aerobic exercise followed by transcranial direct current stimulation (tDCS), and (2) physical inactivity followed by tDCS and a third session will assess the effects of exercise alone. Moderate aerobic exercise will consist of 20 minutes of cycling on an ergometer.
Corticospinal excitability and intracortical and sensorimotor circuit function will be assessed using transcranial magnetic stimulation (TMS) before and after each intervention. Neuroplasticity will be evaluated by measuring changes in motor evoked potentials recorded from a hand muscle of the dominant side.
The primary objective is to determine whether aerobic exercise enhances tDCS-induced plasticity, and whether this enhancement differs between young and older adults. Secondary objectives include evaluating age-related differences in intracortical inhibitory and facilitatory mechanisms and sensorimotor integration processes.
By improving understanding of how exercise interacts with brain stimulation to modulate motor cortex plasticity, this study may help inform strategies aimed at preserving motor function and functional independence in aging populations.
Study Overview
Status
Detailed Description
Aging is associated with structural and functional changes in the central nervous system that may negatively impact motor control, postural stability, upper-limb coordination, and adaptive motor behavior. These functional alterations are partly attributed to changes in cortical excitability and reduced efficiency of intracortical inhibitory and sensorimotor circuits within the primary motor cortex (M1). Such modifications may contribute to a decline in neuroplasticity, defined as the capacity of the brain to reorganize in response to internal or external stimuli.
Neuroplasticity plays a critical role in motor learning and adaptation and is therefore essential for maintaining functional autonomy in older adults. Identifying interventions capable of enhancing or preserving neuroplasticity with aging represents an important clinical and societal challenge. Aerobic physical exercise has emerged as a promising non-pharmacological strategy to modulate cortical excitability and promote neuroplasticity.
The primary objective of this study is to assess the effect of a single session of moderate aerobic exercise on neuroplasticity induced by transcranial direct current stimulation (tDCS) in older adults, compared with young adults. The secondary objective is to examine the influence of exercise on intrinsic intracortical circuits and sensorimotor integration mechanisms within M1.
Study Design :
This is a monocentric exploratory study where each participant will complete three experimental sessions separated by at least one week :
Session 1 and Session 2 (randomized crossover design):
- Condition A : 20 minutes of moderate aerobic exercise followed by tDCS.
- Condition B : 20 minutes of seated rest followed by tDCS. The order of these two conditions will be randomized. Each participant serves as their own control.
Session 3:
- Assessment of the effects of aerobic exercise alone (without tDCS).
Experimental Procedures :
After providing written informed consent, participants undergo baseline assessments including questionnaires documenting physical activity level, handedness, and pain level.
Participants are comfortably seated, and surface electromyography (EMG) electrodes are placed over the abductor pollicis brevis (APB) muscle of the dominant hand. Transcranial magnetic stimulation (TMS) is delivered over M1 corresponding to the dominant hand representation. The optimal stimulation site (hotspot) and resting motor threshold (RMT) are determined.
Corticospinal excitability is assessed using single-pulse TMS at increasing intensities to construct input-output (I/O) recruitment curves. Motor evoked potentials (MEPs) are recorded from the APB muscle. A Boltzmann sigmoidal function is used to model I/O curves and extract parameters including slope, plateau, and S50. The primary outcome measure is the slope of the I/O curve, reflecting corticospinal recruitment gain.
Neuroplasticity is evaluated by comparing corticospinal excitability before and after a 20-minute session of anodal tDCS applied over the dominant M1 (2 mA). Changes in I/O curve parameters after tDCS, with or without prior physical exercise, serve as indicators of induced plasticity.
Intracortical inhibitory and facilitatory mechanisms are assessed using paired-pulse TMS protocols :
- Short-interval intracortical inhibition (SICI)
- Intracortical facilitation (ICF)
- Long-interval intracortical inhibition (LICI)
Sensorimotor integration is evaluated using paired peripheral nerve stimulation (median nerve at the wrist) combined with TMS to measure :
- Short-latency afferent inhibition (SAI)
- Long-latency afferent inhibition (LAI)
- Afferent-induced facilitation (AIF) Outcome measures are expressed as ratios of conditioned to unconditioned MEP amplitudes.
Aerobic Exercise Intervention :
Moderate aerobic exercise consists of 20 minutes of cycling on an ergometer at 60 to 70 revolutions per minute. Exercise intensity is individualized to correspond to approximately 50% of heart rate reserve (moderate intensity), monitored throughout the session.
The estimated duration of each experimental session is as follows :
- Session 1 (2h05) : Information, consent, and questionnaires (10 minutes), electrode placement (5 minutes), baseline recordings (35 minutes), 20 minutes of aerobic exercise or seated rest (randomized), 20 minutes of tDCS, and 35 minutes of post-intervention recordings.
- Session 2 (1h05) : Same procedure as Session 1 without information, consent, or questionnaires. Participants complete the alternate condition (exercise or rest), followed by tDCS and post-intervention recordings.
- Session 3 (1h35) : Preparation (5 minutes), baseline recordings (35 minutes), 20 minutes of aerobic exercise, and 35 minutes of post-exercise recordings.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Hervé Devanne, Pr
- Phone Number: +33 6 76 32 12 84
- Email: herve.devanne@univ-littoral.fr
Study Contact Backup
- Name: Laurence Jones, MSc
- Phone Number: +33 6 11 77 53 23
- Email: laurence.jones@etu.univ-littoral.fr
Study Locations
-
-
Nord
-
Loos, Nord, France, 59120
- Recruiting
- Eurasport
-
Contact:
- Serge Berthoin, PhD
- Phone Number: +33 3 74 00 82 02
- Email: serge.berthoin@univ-lille.fr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Men or women aged 20 to 35 for the younger group and 65 to 80 for the older group.
- Healthy right-handed or left-handed subjects.
- Subjects who have signed an informed consent form.
- Ability to understand spoken and written French to follow study procedures.
- Subjects affiliated with or beneficiaries of a social security system.
Exclusion Criteria:
- History of psychaitric disorders : individuals with mental retardation or severe impairment of cognitive, behavioral, or emotional functions that prevent them from understanding the protocol and signing the informed consent form.
- Neurological history (epilepsy, stroke, brain or spinal cord surgery, and history of neurological diseases affecting motor skills and sensitivity, such as multiple sclerosis, neurodegenerative diseases such as Parkinson's or Alzheimer's).
- Inability to give informed consent (e.g., dementia, significant hearing impairment, insufficient language proficiency).
- Contraindications to TMS and tDCS : uncontrolled epilepsy, intracranial metallic foreign body, hearing aid or cochlear implant, implanted stimulator or pump, scalp skin lesion, high intracranial pressure, cerebrospinal fluid shunt).
- Presence of a cardiac pacemaker or other implanted electronic medical device.
- Use of psychotropic drugs.
- Individuals under legal guardianship or curatorship.
- Pregnant and breastfeeding women.
- Inability or recognized contraindication to physical activity.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Physical Activity + tDCS
Participants undergo baseline assessments of corticospinal excitability and intracortical and sensorimotor circuits using transcranial magnetic stimulation (TMS). They then perform 20 minutes of moderate-intensity aerobic exercise on a cycle ergometer at 50% of heart rate reserve, maintaining a cadence of 60 to 70 revolutions per minute (rpm). Immediately after exercise, participants receive 20 minutes of anodal transcranial direct current stimulation (tDCS) applied over the primary motor cortex (M1). Post-intervention TMS assessments are conducted using the same single- and paired-pulse paradigms to evaluate changes in corticospinal excitability and intracortical and sensorimotor circuits following the combined aerobic exercise and anodal tDCS intervention. |
Participants perform 20 minutes of moderate-intensity cycling on a cycle ergometer at 50% of heart rate reserve, maintaining a cadence between 60 and 70 revolutions per minute (rpm).
Single- and paired-pulse TMS is applied over the primary motor cortex (M1) to assess corticospinal excitability and intracortical inhibitory and facilitatory mechanisms and sensorimotor circuit function.
Motor evoked potentials (MEPs) are recorded from the abductor pollicis brevis (APB) muscle of the dominant hand.
Anodal transcranial direct current stimulation (tDCS) is delivered for 20 minutes over the primary motor cortex (M1) at a current intensity of 2mA.
|
|
Experimental: Physical Inactivity + tDCS
Participants undergo baseline assessments of corticospinal excitability and intracortical and sensorimotor circuits using transcranial magnetic stimulation (TMS). They then remain seated for 20 minutes and watch a silent video of natural waterfall scenes without narration. This condition is designed to provide a standardized and controlled resting period comparable across participants. Immediately after, participants receive 20 minutes of anodal transcranial direct current stimulation (tDCS) applied over the primary motor cortex (M1). Post-intervention TMS assessments are conducted using the same single- and paired-pulse paradigms to evaluate changes in corticospinal excitability and intracortical and sensorimotor circuits following the combined physical inactivity and anodal tDCS intervention. |
Single- and paired-pulse TMS is applied over the primary motor cortex (M1) to assess corticospinal excitability and intracortical inhibitory and facilitatory mechanisms and sensorimotor circuit function.
Motor evoked potentials (MEPs) are recorded from the abductor pollicis brevis (APB) muscle of the dominant hand.
Anodal transcranial direct current stimulation (tDCS) is delivered for 20 minutes over the primary motor cortex (M1) at a current intensity of 2mA.
Participants remain seated for 20 minutes while watching a silent video of natural waterfall scenes without narration.
|
|
Experimental: Physical Activity
Participants undergo baseline assessments of corticospinal excitability and intracortical and sensorimotor circuits using transcranial magnetic stimulation (TMS).
They then perform 20 minutes of moderate-intensity aerobic exercise on a cycle ergometer at 50% of heart rate reserve, maintaining a cadence of 60 to 70 revolutions per minute (rpm).
Immediately after exercise, post-intervention TMS assessments are conducted using the same single- and paired-pulse paradigms to evaluate changes in corticospinal excitability and intracortical and sensorimotor circuits following aerobic exercise alone.
|
Participants perform 20 minutes of moderate-intensity cycling on a cycle ergometer at 50% of heart rate reserve, maintaining a cadence between 60 and 70 revolutions per minute (rpm).
Single- and paired-pulse TMS is applied over the primary motor cortex (M1) to assess corticospinal excitability and intracortical inhibitory and facilitatory mechanisms and sensorimotor circuit function.
Motor evoked potentials (MEPs) are recorded from the abductor pollicis brevis (APB) muscle of the dominant hand.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Corticospinal excitability
Time Frame: Assessed at baseline and immediately post-intervention during each of the three experimental sessions (aerobic exercise + tDCS, physical inactivity + tDCS and aerobic exercise alone).
|
Corticospinal excitability will be assessed using transcranial magnetic stimulation (TMS) applied to the primary motor cortex.
Motor evoked potentials (MEPs) are recorded using surface electromyography from the abductor pollicis brevis (APB) muscle of the dominant hand.
Single pulses of increasing intensity will be delivered to establish an input-output (I/O) recruitment curve.
The stimulation intensity will be increased in steps of 3 to 5%, and 10 stimuli will be delivered per stimulation intensity.
I/O curves will be fitted using a Boltzmann sigmoid function.
Three parameters will be derived : slope, plateau and S50.
These parameters will be compared across experimental conditions.
The primary outcome will be the slope of the I/O curve, reflecting the recruitment rate of neurons in the corticospinal tract, indicating the level of corticospinal excitability.
|
Assessed at baseline and immediately post-intervention during each of the three experimental sessions (aerobic exercise + tDCS, physical inactivity + tDCS and aerobic exercise alone).
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Intracortical and sensorimotor circuits of M1
Time Frame: Baseline and post-intervention
|
Sensorimotor circuits of the primary motor cortex (M1) will be assessed using paired-pulse transcranial magnetic stimulation (TMS) applied over the M1 controlling the dominant hand. Short- and long-interval intracortical inhibition and facilitation (SICI, ICF, LICI) : A subthreshold conditioning stimulus (80% RMT) will precede a suprathreshold test stimulus (1mV MEP) at specific interstimulus intervals to quantify intracortical inhibitory and facilitatory processes. Outcome measures are expressed as the ratio of conditioned to unconditioned MEP amplitude. Sensorimotor afferent circuits (SAI, LAI, AIF) : Electrical stimulation of the median nerve at the wrist (SC) will precede TMS over M1 (ST) at defined intervals to evaluate afferent-mediated inhibition or facilitation. Outcome measures are the ratio of conditioned to unconditioned MEP amplitude. |
Baseline and post-intervention
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Global Physical Activity Questionnaire
Time Frame: Baseline
|
The Global Physical Activity Questionnaire (GPAQ) is used to assess levels of physical activity.
Designed for adults, this standardized questionnaire comprises 16 items (P1 to P16) that gather information about physical and sports activities during a typical week.
The GPAQ explores three specific categories : activities carried out in a professional context, active travel and leisure activities.
It also takes into account time spent sitting, thus reflecting sedentary behaviors.
For each of these categories, the frequency, duration, and intensity of activities are recorded.
|
Baseline
|
|
Edinburgh Handedness Inventory
Time Frame: Baseline
|
Measuring handedness is particularly important in studies using transcranial magnetic stimulation (TMS), as manual dominance is often associated with functional and structural asymmetries in the brain.
Accurate identification of the dominant hand allows for better targeting of cortical regions of interest and standardization of the interpretation of neurophysiological results.
This questionnaire includes a series of common activities (writing, throwing, using scissors, etc.) for which the participant indicates which hand they use most frequently.
|
Baseline
|
|
Numeric Pain Rating Scale
Time Frame: The level of pain will be assessed before each session. If pain is present, the participant will re-evaluate it at the end of each session.
|
The Numeric Rating Scale (NRS) will be administered to assess the presence and intensity of pain in daily life, particularly in older participants who may experience pain.
This measure is included to document baseline pain status and to explore potential interactions between pain and neurophysiological outcomes.
In participants reporting no pain, the scale will not be further analyzed.
|
The level of pain will be assessed before each session. If pain is present, the participant will re-evaluate it at the end of each session.
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Behavior
- Motor Activity
- Sedentary Behavior
- Motor Activity
- Movement
- Musculoskeletal Physiological Phenomena
- Musculoskeletal and Neural Physiological Phenomena
- Therapeutics
- Behavioral Disciplines and Activities
- Magnetic Field Therapy
- Electric Stimulation Therapy
- Convulsive Therapy
- Psychiatric Somatic Therapies
- Electroshock
- Psychological Techniques
- Exercise
- Transcranial Magnetic Stimulation
- Transcranial Direct Current Stimulation
Other Study ID Numbers
- 2025-A01291-48
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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