fMRI Study on Cerebral Localization and Network Mechanisms of rTMS in Chronic Ankle Instability Treatment

A Study on Precise Cerebral Localization and Network Mechanisms of Repetitive Transcranial Magnetic Stimulation in Treating Chronic Ankle Instability Based on High-resolution Functional Magnetic Resonance Imaging

Chronic ankle instability (CAI) is a common sports injury that often leads to recurrent injuries and functional deficits. While conventional rehabilitation can restore ankle stability, the underlying neurophysiological mechanisms remain poorly understood, and the long-term efficacy of current treatments is limited. This study aims to investigate the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) in combination with conventional ankle stability training for CAI and to evaluate its impact on ankle-stabilizing muscle activation and cerebral cortex excitability.

The study design is a single-center, randomized, single-blind, parallel-controlled trial. Participants with CAI will be randomly assigned to either an ankle stability training plus real rTMS group or an ankle stability training plus sham rTMS group. The primary outcome measure is the Cumberland Ankle Instability Tool (CAIT) score, which assesses the severity of ankle instability. Secondary outcomes include the Karlsson-Peterson Ankle Function Score (KPAFS), American Orthopedic Foot and Ankle Society Score (AOFAS), surface electromyography (sEMG) data, and task-based functional magnetic resonance imaging (fMRI) data. These secondary outcomes will provide a comprehensive evaluation of ankle function, muscle activation patterns, and neural activity changes.

The intervention will consist of a 4-week program, with participants receiving rTMS sessions three times per week. Each rTMS session will target key brain regions. The ankle stability training will include exercises designed to improve strength, balance, and proprioception. The sham rTMS group will receive identical ankle stability training but with a placebo rTMS protocol to ensure blinding.

Data will be collected at baseline, 2 weeks, and 4 weeks. The primary outcome, CAIT score, will be used to assess the overall improvement in ankle stability. The KPAFS and AOFAS scores will provide additional measures of ankle function and pain. sEMG data will be collected during specific functional tasks to evaluate the activation patterns of the tibialis anterior, peroneus longus, and other relevant muscles. Task-based fMRI will be used to assess changes in brain activity in motor and sensory areas before and after the intervention.

Statistical analyses will be performed using SPSS 22.0. Data will be presented as mean ± standard deviation. Between-group differences will be compared using independent samples t-tests, and overall differences across time points will be assessed via two-way repeated-measures ANOVA or mixed-effects models. Post-hoc analyses will be conducted to identify specific time points and conditions where significant differences occur.

The study timeline spans from March 2025 to December 2026, including participant recruitment, intervention implementation, data collection, and analysis, as well as manuscript drafting. This research aims to provide new insights into the neurophysiological mechanisms of CAI and to offer a novel, evidence-based approach to the rehabilitation of CAI, potentially improving long-term outcomes and reducing the risk of recurrent injuries.

Inclusion Criteria:

1. Age 18-60 years.
2. History of at least one significant ankle sprain within the past 12 months, accompanied by inflammatory response (including pain resulting in at least one day of restricted physical activity).
3. The most recent ankle sprain must have occurred more than 3 months prior to enrollment.
4. Self-reported symptoms of ankle instability, defined by one or more of the following: At least two episodes of "giving way" in the affected ankle within the past 6 months; Recurrent sprains (≥2 documented sprains in the same ankle); Subjective perception of instability confirmed by any one of the following validated instruments: Ankle Instability Instrument (AII): ≥5 affirmative responses; Cumberland Ankle Instability Tool (CAIT): Score <24; Identification of Functional Ankle Instability (IdFAI): Score >11.
5. Foot and Ankle Ability Measure (FAAM): Activities of Daily Living (ADL) subscale <90%; FAAM Sports subscale <80%; Foot and Ankle Outcome Score (FAOS): Scores <75% in ≥3 subcategories.

Exclusion Criteria:

1. Chronic ankle instability caused by bilateral ankle sprains;
2. History of lower extremity musculoskeletal or neurological surgery;
3. History of lower extremity fractures;
4. Acute musculoskeletal injuries in other lower extremity joints within 3 months that compromised joint integrity and function, resulting in ≥1 day of interrupted daily or sports activities;
5. Concomitant severe systemic diseases (cardiac, pulmonary, hepatic, renal, etc.);
6. Severe psychiatric disorders or cognitive impairments;
7. Presence of metal implants or inability to tolerate MRI examinations.
8. Patient refusal to participate.