Neuromodulation for Exercise Adherence

Background: Fall-related hospitalizations and consequent morbidity and mortality continue to
rise despite the availability for over two decades of evidence-based fall-prevention
programs. This is a major problem since more than 2.5 million older adults are treated
annually for fall-related injuries in the US. Fall-prevention programs focusing on strength
and balance exercises have been successful in facility settings but exercise programs are
ineffective at home due to lack of adherence. Estimates indicate that only 1 in 5 individuals
adhere to home exercise programs for fall prevention. Thus, there is an urgent need to
improve adherence to exercise performed at home by older adults seeking to improve balance
for the sake of fall prevention. Behavioral interventions have failed to consistently improve
adherence to exercise. Biological reasons for poor exercise adherence, such as executive
dysfunction, have not been explored. Adherence to long-term exercise is dependent on
executive function (EF), which is controlled by the [dorsolateral prefrontal cortex (DLPFC)]
of the brain. EF influences choices in scheduling, forgoing competing activities, enduring
subtle costs of time and inconvenience, and the ability to delay gratification. Repetitive
transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation increasingly used
for neural network specific interventions. rTMS of the DLPFC improves EF, memory, motivation,
and mental flexibility. rTMS studies to date have stimulated the motor cortex for gait and
balance improvements. The role of DLPFC in exercise adherence has not been explored. The
proposed study will be the first to test DLPFC stimulation for improving exercise adherence.

Objective: The study objective is to determine the effects of rTMS treatment of the
dorsolateral prefrontal cortex compared to sham on: [1. Short-term (2-wk) changes in
executive function;] 2. Long-term (24-wk) adherence to a home-based exercise program; 3.
Long-term (24-wk) changes in balance and gait; and [4. Short-term (2-wk) changes in
self-efficacy and delay discounting.]

Methods: Sedentary community-dwelling older Veterans (age 65 years, [N=106]) will participate
in a double-blind randomized sham-controlled three-phase study. The proposed study will use
Nintendo Wii-Fit exercises. Phase I will include two weeks of facility-based exercise for
safety assessment and learning the program, followed by 12 weeks of home-based exercises.
[Subjects with poor adherence and those with good adherence with low EF] will then be
randomized to rTMS or sham treatments. Phase II will include ten consecutive weekdays of rTMS
or sham treatment along with exercise training for subjects with poor adherence [and for
those with good adherence and low EF] and continuation of home-based exercises for those with
good adherence and EF. Phase III includes 24-weeks of a home-based exercise program. All
subjects will exercise for 45 minutes five days/week. [Objective measure of adherence
collected from Wii-Fit console and Conner's continuous performance test for EF will be the
primary outcome measures.] Balance and gait will be assessed. [Self-efficacy, delay
discounting along with fear of falls, and falls incidence will be assessed. Outcome measures
will be assessed at baseline, and at 14, 16, and 40 weeks.]

Significance: This project will have a major impact in improving adherence to an exercise
program and in turn, improve balance in sedentary community-dwelling older Veterans. At the
end of the proposed project, the investigators will gain knowledge about the efficacy of rTMS
in improving EF and exercise adherence. Knowledge gained about the adherence to home-based
exercises would be applicable to multiple conditions such as diabetes. Since Wii-Fit and rTMS
are readily available, translation of the study results to clinical practice would be
expeditious.

Inclusion Criteria:

- Sedentary Community Dwelling Veterans age 60 years

- Have TV at home

- Subjects reporting spending long periods of time in sedentary behavior by answering
affirmatively to the question: 'For most days, do you feel you sit for too long (6-8
hours or more a day)?

- Some examples might include when watching TV, working at the computer / laptop or
when doing sitting-based hobbies such as reading and sewing' will be included

Exclusion Criteria:

GENERAL EXCLUSION CRITERIA

- Those that participate in regular physical activity for at least 30 minutes five or
more days of the week

EXCLUSIONARY DUE TO Wii-Fit Exercises

- Use of wheel chair for mobility

- Cognitive impairment [Montreal Cognitive Assessment (MoCA < 26)]

- Weight 325 lbs. (weight restriction of the Wii-Board)

- Absolute contraindications to exercise per The American College of Sports Medicine
guidelines

- Those with medical conditions that in the opinion of the study physician are likely to
compromise safe participation

EXCLUSIONARY DUE TO rTMS

- Taking medications known to increase risk of seizures from 2012 Beers criteria such as
bupropion, chlorpromazine, clozapine.

- Taking other medications known to increase risk of seizures such as tricyclic
antidepressants.

- Taking ototoxic medications: Aminoglycosides, CisplatinHistory of seizures/ seizures
in first degree relatives

- Those with implanted device

- History of stroke, aneurysm, or cranial neurosurgery

- History of bipolar disorder

- History of abnormal electroencephalogram (EEG)