CONTROL Walking Study

Cerebral Networks of Locomotor Learning and Retention in Older Adults

Older adults often experience substantial deficits in walking ability, especially for walking tasks that are more complex such as obstacle crossing. This is due in part to changes in the brain that make performance of physical and cognitive tasks more difficult. Rehabilitation can help to improve walking ability, but effective rehabilitation is time consuming and expensive. New approaches are needed to improve the efficiency of rehabilitation so that gains in walking ability are widely attainable. A promising strategy is to focus on enhancing motor learning, which is defined as improved ability to perform a motor task due to practice or experience. The investigators will investigate the use of non-invasive brain stimulation to increase motor learning and retention of the newly learned walking skills. The investigators will also use neuroimaging to assess brain characteristics that explain how motor learning works. The knowledge gained from this study is expected to contribute to better understanding of mechanistic targets and intervention approaches to improve rehabilitation of walking.

Study Overview

• Status: Completed
• Conditions: Aging
• Intervention / Treatment: Behavioral: practice of a complex walking task; Device: Active transcranial direct current stimulation (Active tDCS); Device: Sham transcranial direct current stimulation (Sham tDCS)

Detailed Description

Aging often leads to substantial declines in walking function, especially for walking tasks that are more complex such as obstacle crossing. This is due in part to a lack of continued practice of complex walking (sedentary lifestyle) combined with age-related deficits of brain structure and the integrity of brain networks. Neurorehabilitation can contribute to recovery of lost walking function in older adults, but major and persistent improvements are elusive. A cornerstone of neurorehabilitation is motor learning, defined as an enduring change in the ability to perform a motor task due to practice or experience. Unfortunately, in most clinical settings, the time and cost demands of delivering a sufficiently intensive motor learning intervention is not feasible. There is a need for research to develop strategies for enhancing motor learning of walking ("locomotor learning") in order to improve the effectiveness of neurorehabilitation.

The objective of this study is to use non-invasive brain stimulation to augment locomotor learning and to investigate brain networks that are responsible for locomotor learning in mobility-compromised older adults. The investigators have shown that frontal brain regions, particularly prefrontal cortex, are crucial to control of complex walking tasks. The investigators' neuroimaging and neuromodulation studies also show that prefrontal cortex structure and network connectivity are important for acquisition and consolidation of new motor skills. However, a major gap exists regarding learning of walking tasks. The proposed study is designed to address this gap. The investigators' pilot data from older adults shows that prefrontal transcranial direct current stimulation (tDCS) administered during learning of a complex obstacle walking task contributes to multi-day retention of task performance. In the proposed study the investigators will build upon this pilot work by conducting a full scale trial that also investigates mechanisms related to brain structure, functional activity, and network connectivity. The investigators will address the following specific aims:

Specific Aim 1: Determine the extent to which prefrontal tDCS augments the effect of task practice for retention of performance on a complex obstacle walking task.

Specific Aim 2: Determine the extent to which retention of performance is associated with individual differences in baseline and practice-induced changes in brain measures (including gray matter volume and brain network segregation).

Specific Aim 3: Investigate the extent to which tDCS modifies resting state network segregation.

The investigators anticipate that prefrontal tDCS will augment retention of locomotor learning, and that the data will provide the first evidence of specific brain mechanisms responsible for locomotor learning/retention in older adults with mobility deficits. This new knowledge will provide a clinically feasible intervention approach as well as reveal mechanistic targets for future interventions to enhance locomotor learning and retention.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608-1135
      • North Florida/South Georgia Veterans Health System, Gainesville, FL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• age 65 years or older
• preferred 10m walking speed < 1.1 m/s
• self-report of "some difficulty with walking tasks, such as becoming tired when walking a quarter mile, or when climbing two flights of stairs, or when performing household chores."
• Willingness to be randomized to either study group and to participate in all aspects of study assessment and intervention

Exclusion Criteria:

• Diagnosed neurological disorder or injury of the central nervous system, or observation of symptoms consistent with such a condition (Alzheimer's, Parkinson's, stroke, etc.)
• Contraindications to non-invasive brain stimulation (e.g., metal in head, wound on scalp)
• Contraindications to magnetic resonance imaging (e.g., metal in body, claustrophobia, etc).
• Use of medications affecting the central nervous system
• severe arthritis, such as awaiting joint replacement
• severe obesity (body mass index > 35)
• current cardiovascular, lung or renal disease; diabetes; terminal illness
• myocardial infarction or major heart surgery in the previous year
• cancer treatment in the past year, except for nonmelanoma skin cancers and cancers having an excellent prognosis (e.g., early stage breast or prostate cancer)
• current diagnosis of schizophrenia, other psychotic disorders, or bipolar disorder
• uncontrolled hypertension at rest (systolic > 180 mmHg and/or diastolic > 100 mmHg)
• bone fracture or joint replacement in the previous six months
• current participation in physical therapy for lower extremity function or cardiopulmonary rehabilitation
• current enrollment in any clinical trial
• difficulty communicating with study personnel, and/or non-English speaking
• planning to relocate out of the area during the study period
• clinical judgment of investigative team regarding safety or non-compliance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active tDCS; 20 minutes of mild electrical stimulation delivered to the frontal region of the brain during practice of a complex walking task	Behavioral: practice of a complex walking task; walking over obstacles; Device: Active transcranial direct current stimulation (Active tDCS); mild electrical stimulation delivered to the frontal region of the brain
Sham Comparator: Sham tDCS; 30 seconds of mild electrical stimulation delivered to the frontal region of the brain during practice of a complex walking task	Behavioral: practice of a complex walking task; walking over obstacles; Device: Sham transcranial direct current stimulation (Sham tDCS); 30 seconds of mild electrical stimulation delivered to the frontal region of the brain

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Walking Speed Change From Baseline	Change in the fastest safe walking speed over a complex walking course	Measured at follow up visit (approximately three weeks after baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prefrontal Cortex Gray Matter Volume Change From Baseline	Change in the volume of gray matter in the prefrontal cortex, as measured by MRI	Measured at follow up visit (approximately three weeks after baseline)
Brain Resting State Network Segregation (Z-transformed Correlation Coefficient)	Resting-state functional MRI was used to measure the segregation of large-scale brain networks. Connectivity strength was quantified using Fisher z-transformed correlation coefficients, averaged across regions of interest within each network. Results are reported as mean z-scores for each group. Higher values reflect greater segregation (i.e., stronger within-network compared to between-network connectivity).	Measured at follow up visit (approximately three weeks after baseline)

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: David J. Clark, DSc, North Florida/South Georgia Veterans Health System, Gainesville, FL

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): August 1, 2024
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: December 28, 2018
• First Submitted That Met QC Criteria: December 28, 2018
• First Posted (Actual): December 31, 2018

Study Record Updates

• Last Update Posted (Estimated): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: electrical stimulation; aging; walking; brain
• Other Study ID Numbers: E3115-R; I01RX003115 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A Limited Dataset will be created and shared pursuant to a Data Use Agreement appropriately limiting use of the dataset and prohibiting the recipient from identifying or re-identifying (or taking steps to identify or re-identify) any individual whose data are included in the dataset.
• IPD Sharing Time Frame: The Limited Dataset will be completed after the study is completed and primary/secondary data accepted for publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

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