Paired inhibitory stimulation and gait training modulates supplemental motor area connectivity in freezing of gait.

INTRODUCTION: Freezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD). Evidence suggests patients with FOG have increased cortical control of gait. The supplementary motor area (SMA) may be a key structure due to its connectivity with locomotor and cognitive networks. The objectives of this study were to determine (1) if SMA connectivity is disrupted in patients with FOG and (2) if "inhibitory" repetitive transcranial magnetic stimulation can decrease maladaptive SMA connectivity. METHODS: Two experiments were performed. In experiment 1 resting-state (T2* BOLD imaging) was compared between 38 PD freezers and 17 PD controls. In experiment 2, twenty PD patients with FOG were randomized to either 10 sessions of real or sham rTMS to the SMA (1 Hz, 110% motor threshold, 1200 pulses/session) combined with daily gait training. RESULTS: (Experiment 1) Freezers had increased connectivity between the left SMA and the vermis of the cerebellum and decreased connectivity between the SMA and the orbitofrontal cortex (pFDR-corr <0.05). (Experiment 2) 10 sessions of active TMS reduced SMA connectivity with the anterior cingulate, angular gyrus and the medial temporal cortex, whereas sham TMS did not reduce SMA connectivity. From a behavioral perspective, both groups showed nFOG-Q improvements (F(4, 25.7) = 3.87, p = 0.014). CONCLUSIONS: The SMA in freezers is hyper-connected to the cerebellum, a key locomotor region which may represent maladaptive compensation. In this preliminary study, 1 Hz rTMS reduced SMA connectivity however, this was not specific to the locomotor regions. Intervention outcomes may be improved with subject specific targeting of SMA.

Lessons Learned: The Difficulties of Incorporating Intensity Principles Into Inpatient Stroke Rehabilitation.

OBJECTIVE: The objective of this study was to determine the feasibility of a rehabilitation approach focusing on cardiovascular, strength, and gait training intensity in the inpatient rehabilitation setting after a new onset of stroke. We additionally aimed to determine the efficacy of this intensity-based program on rehabilitation outcomes compared with usual care. DESIGN: Participants were pseudo-randomized to an intensity-based program focusing on gait, cardiovascular, and strength training or to usual care. Outcomes included FIM, 10-meter walk, 2-minute walk, timed Up and Go test, 5-time sit-to-stand test, and Tinetti balance assessment. INTERVENTION: The intervention consisted of 6 20-minute sessions per week dedicated to intensity of activity: 2 each for walking, cardiovascular training, and strength training. PARTICIPANTS: Patients (N=49) with new onset stroke admitted to inpatient rehabilitation over the course of 1 year. SETTING: Four inpatient rehabilitation facilities with comprehensive neurologic rehabilitation teams. RESULTS: Thirty-five individuals (16 intervention, 19 controls) completed all testing. Subject compliance to the intensity intervention demonstrated completion of approximately half the prescribed sessions. All outcomes improved significantly from admission to discharge, and a significant interaction between treatment group and time was observed for the 2-minute walk and the Tinetti balance assessment. The 2-minute walk, Tinetti balance assessment, 10-meter walk, and FIM demonstrated between-group effect sizes greater than 0.60 in favor of the intervention group. CONCLUSIONS: The intensity-based protocol was safe, and several measures demonstrated efficacy when compared with usual care. Results may have been limited by poor program compliance, showing a need to identify and ameliorate obstacles to integration of comprehensive intensity-based programs addressing endurance, strength, and gait training. Applying physiological principles of exercise to acute stroke rehabilitation demonstrates great promise for improving independent physical function.