Posted December 5, 2023

Angelo Quartarone, M.D., University of Messina
M. Felice Ghilardi, M.D., The City College of New York

Medical researchers have long understood that exercise reduces the motor and cognitive symptoms associated with Parkinson’s disease (PD) and may even slow disease progression. One widely recognized exercise program for PD patients is a 4-week program of intensive repeated exercise called the Multidisciplinary Intensive Rehabilitation Treatment (MIRT). MIRT consists of cardiovascular, gait, and balance exercises, as well as occupational and speech therapies conducted in a hospital setting. Researchers do not fully understand why MIRT is effective in treating PD symptoms, although one theory is that it improves the ability of the brain and spinal cord to rewire themselves – a phenomenon called plasticity – thereby slowing the progression of the disease. In fiscal year 2018 (FY18), the Neurotoxin Exposure Treatment Parkinson’s (NETP) program awarded Drs. Quartarone and Ghilardi with an Investigator-Initiated Research Award – Partnering PI (Principal Investigator) Option to test his hypothesis that MIRT works by improving memory formation in PD patients, thus restoring the brain’s ability to learn and remember motor activity. In FY22, the U.S. Congress transitioned the NETP to the Parkinson’s Research Program, which now manages this award.

Movements are accompanied by brain activity recorded with electroencephalogram (EEG) in frequency defined as beta (13-30 Hz) and gamma (>30 Hz) ranges. In a recent study, Drs. Quartarone and Ghilardi reviewed the results of their studies in humans to understand the meaning and the implication of the brain activity associated with movement in the beta range.¹ Their previous work in normal subjects demonstrated that activity in the gamma range recorded from the brain with EEG before and during the movement is proportional to the speed and force of the movement produced.² Instead, movement-related brain activity in the beta range does not depend on the force and speed of the movement,^3,4 but rather, it increases with practice,⁵ a phenomenon that is not seen in patients with PD.⁴ Also, in normal subjects, a period of rest, even without sleep, can restore beta power values to the baseline levels.⁴ Based on these results and those of other studies in animals, Dr. Quartarone and colleagues propose that the practice-related increases of beta power must reflect the amount of energy used for the formation of new brain connections, a process that is at the base of plasticity, learning, and brain repair in neurological diseases.¹ Therefore, the abnormal finding of brain activity in the beta range during movement, as well as the decreased skill formation found in PD, may result from deficiency in consumption, availability, and regulation of energy mechanisms present in PD.¹ If proven correct, this hypothesis can have three important implications.

First, it can guide the development of new therapies and strategies based on the improvement of the supply and use of energy to ameliorate the symptoms of PD and other injuries of the brain. These approaches include aerobic exercise, a practice that in PD is associated with a slow-down of disease progression and many benefits on the brain metabolism. Second, it will contribute to a better understanding of the mechanisms through which rehabilitative exercises such as MIRT affect brain and spinal cord plasticity, thus leading to the development of new and improved rehabilitation tools and therapies for the treatment of PD. Lastly, this hypothesis is important to address new research efforts to study the genes involved in energy regulation in PD, thus shedding light on the origin and causes of this disease that are still undefined.

References:

¹Ghilardi MF, Tatti E, and Quartarone A. 2021. Beta power and movement-related beta modulation as hallmarks of energy for plasticity induction: Implications for Parkinson's disease. Parkinsonism & Related Disorders 88:136-139. doi: 10.1016/j.parkreldis.2021.05.018. Epub 2021 Jun 3. PMID: 34144879

²Tatti E, Ferraioli F, Cacciola A, et al. 2022. Modulation of gamma spectral amplitude and connectivity during reaching predicts peak velocity and movement duration. Frontiers in Neuroscience 16:836703

³Peter J, Ferraioli F, Mathew D, et al. 2022. Movement-related beta ERD and ERS abnormalities in neuropsychiatric disorders. Frontiers in Neuroscience 16:1045715.

⁴Tatti E, Ricci S, Nelson AB, et al. 2020. Prior practice affects movement-related beta modulation and quiet wake restores it to baseline. Frontiers in Systems Neuroscience 14:61

⁵Tatti E, Ferraioli F, Peter J, et al. 2021. Frontal increase of beta modulation during the practice of a motor task is enhanced by visuomotor learning. Sci Rep 11(1):17441. doi: 10.1038/s41598-021-97004-0. Author Correction: 2021. Frontal increase of beta modulation during the practice of a motor task is enhanced by visuomotor learning. Scientific Reports 11(1):24064. doi: 10.1038/s41598-021-03659-0.

Link:
Public and Technical Abstracts: Exercise and Plasticity in PD: Functional and Structural Evidence in the Cortex and the Spinal Cord

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