Determining the effects of non-invasive brain stimulation to improve quadriceps muscle function after ACL reconstruction.

/Abstract Quadricep muscle impairments persist for years after anterior cruciate ligament reconstruction (ACLR). They are linked to poor long-term outcomes including the early onset of post-traumatic knee osteoarthritis (PTOA), which is thought to result from altered movement patterns (i.e. walking and running) and persistent quadriceps muscle impairments. Despite use of evidence-based postoperative rehabilitation protocols, the prevalence of PTOA following ACLR remains at approximately 40% after a mean follow-up of 15 years. Thus, approximately 100,000 individuals who undergo ACLR each year will develop PTOA between the ages of 30 and 40 years, imposing a substantial burden on the U.S. healthcare system and significantly impacting quality of life. Recent evidence suggests that lower neural drive, (i.e., lower corticospinal excitably (CSE)), is associated with pronounced quadriceps muscle performance deficits, which are more severe in females recovering from ACLR than in males. Current postoperative rehabilitation protocols do not target lower neural drive, which can be achieved through non-invasive brain stimulation. Thus, the long-term goal of this research is to improve the effectiveness of ACLR rehabilitation. The objective of this R15 project is to determine if neural drive is the critical missing link in ACLR rehabilitation. To meet this objective, we will administer anodal transcranial direct current stimulation (tDCS), a type of non-invasive brain stimulation known to increase CSE. We will then assess whether it improves three measures of quadriceps muscle performance (in Aim 1) and two measures of CSE (in Aim 2). In Aim 3, we will determine the relationship between observed changes in quadriceps muscle performance and CSE in female participants recovering from ACLR. These aims will be achieved using a randomized, triple-blinded clinical trial with 42 female individuals after ACLR between the ages of 18 and 35 years. All participants will receive six sessions of active or sham anodal tDCS while they perform isolated quadriceps exercises on an isokinetic dynamometer. The two measures of CSE (i.e. active motor threshold and the slope of transcranial magnetic stimulation (TMS) induced recruitment curves) will be determined using surface electromyography on the vastus medialis and TMS. Three measures of quadriceps performance (i.e. peak torque normalized to body weight, rate of torque development (RTD) from 0-100ms and 100-200ms, and torque steadiness) will be determined following standard isometric muscle testing on an isokinetic dynamometer with the hips flexed to 90° and the knees flexed to 60°. Statistical analyses will include repeated measures analyses of variance (Aims 1 & 2) and Pearson correlations (Aim 3). Findings from this study will determine if a form of non-invasive brain stimulation improves quadriceps muscle performance, setting the stage for new post-ACLR rehabilitation protocols. Additionally, follow-up research will assess whether the restoration of neural drive corrects altered movement patterns, and in the long-term, ultimately reduces risk of PTOA. Project Number: 1R15HD118518-01 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Ryan Zarzycki | Institution: ARCADIA UNIVERSITY, GLENSIDE, PA | Award Amount: $520,154 | Activity Code: R15 | Study Section: Special Emphasis Panel[ZRG1 MSOS-Q (80)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R15HD11851801