Grant Number:	5R01CA189665-06 Interpret this number
Primary Investigator:	Yue, Guang
Organization:	Kessler Foundation, Inc.
Project Title:	Neurophysiological Evaluation of Training Effect on Cancer-Related Weakness
Fiscal Year:	2019

DESCRIPTION (provided by applicant): Weakness limits mobility and diminishes quality of life in many cancer survivors, especially in those who suffer from late stage of cancer. Early research suggests that high-intensity strength training (HIST) is essential to gain muscle strength. Although participating in HIST posts little difficulties for younger and healthy individuals, such training is intimidating and unsafe for many weak cancer survivors with limited physical abilities. Evidence in recent years, however, has shown that training with high effort (intended muscle contraction) combined with no or little physical exercise can significantly strengthen muscle by increasing brain-to-muscle command, which helps improve motor unit recruitment and activation level. Although the effect of high-effort training on muscle strengthening has been recognized in healthy young and older adults, nothing is known regarding its application to improving strength in weak patients, individuals who may benefit most from participating in this type of training, given difficulties they may face when engaging in conventional HIST. Further, detailed neurophysiological mechanisms behind the phenomenon of high mental effort training- induced strength gain are yet to be determined. Preliminary data from the PI's laboratory show that cancer patients with weakness undergone high-effort motor imagery training can significantly improve their strength. EEG-based movement-related cortical potential measurement demonstrates enhanced descending command to target muscle following such training. These observations led to our fundamental hypothesis that training-induced strength gain resulting from neural adaptations is not dependent on intensity of muscle exercise; rather, it relies primarily on the level of voluntary effort during training regardless o physical exercise intensity. The major goal of this study is to test this hypothesis by training weak cancer survivors with high effort plus moderate intensity (HEMI) and low effort combined with moderate intensity (LEMI) muscle exercises and evaluate strength improvement and underlying neural plasticity after training. The Aims of the study are to determine the effects of HEMI and LEMI training on handgrip strength and level of fMRI-based brain connectivity that modulates the descending command and functional brain-muscle coupling (fBMC) for maximal muscle force. It is hypothesized that the HEMI training will significantly gain strength and elevat the level of cortical network connectivity and fBMC but the LEMI will not. The findings will show that HEMI training is an effective approach to provoke neural plasticity that promotes muscle strength in breast cancer survivors with weakness. Although the results will be acquired from breast cancer patients, the method (HEMI training) is not limited to this patient population for voluntary muscle strengthening.