“Exercise and neuroplasticity in persons living with Parkinson’s disease” was the theme of a pioneering paper on mechanisms of brain plasticity in PD published in the European Journal of Physical and Rehabilitation Medicine by Mark A. Hirsch, PhD. and Becky G. Farley, PT, PhD in 2009. The term “neuroplasticity” can be defined as the brain’s wondrous ability to alter its own structure and function in response to changes in the internal and/or external environment, a process believed to occur in humans throughout life.  The authors reviewed animal and human data on high intensity exercise as it affects the Parkinson’s brain and potential recovery.  According to the authors, “Continuous, deficit targeted, intensive training may confer neuroprotection and thereby slow, stop or reverse the progression of the disease or promote neurorestoration through adaptation of compromised signaling pathways” (Hirsch and Farley, 2009, p. 215) and,“Leading a sedentary lifestyle may be pro-degenerative.”  We caught up with Dr. Hirsch at Carolinas Rehabilitation hospital in Charlotte, North Carolina, where he teaches and conducts research and talked with him about exercise and PD.

Question: What led you to write about exercise, neuroplasticity, and PD?

Hirsch: In the early 1990s it was quite a radical idea to think that no person is too old or too chronically ill to benefit from physical and/or cognitive activity. It was through a series of coincidences (my father lived to 100.5 and began exercising at 78) that I got interested in high intensity exercise (resistance and balance training) and Parkinson’s disease during my time at Florida State University (92-96) and during my post-doctoral fellowship with specialized training in neurorehabilitation research and Parkinson’s disease at Johns Hopkins Hospital.  Back then it was believed that exercise would not improve function in PD and might even be harmful by, for example, increasing the amount of underlying tone. And in the past few years we have learned so much about the benefits of exercise for brain health and PD but have conveyed so little of that information to healthcare professionals or people with PD. So writing this article was an initial attempt to remedy that situation.  Since that time there have been several papers published by our group summarizing and updating the scientific literature on exercise-induced neuroplasticity in PD. But in 2009 the thought of brain plasticity and Parkinson’s was still quite novel and radical! I was particularly inspired by what I learned during a 2008 national conference on physical medicine and rehabilitation, during which Becky and I gave a lecture on exercise, neuroplasticity, and PD.  At the start of the lecture, we asked the about 300 participants, many of whom were physiatrists (physicians specializing in rehabilitation medicine), to raise their hand if they had learned about exercise during their medical training.  All participants raised their hands.  Then we asked participants to keep their hands raised if they had ever prescribed exercise for their PD patients.  About half of the hands remained.  Finally, we asked how many participants prescribed exercise because they believed it to have neuroprotective qualities - and not one hand remained raised.  That day changed my career, and ever since that time my resolve and my commitment became stronger to find a cure for PD. We need to understand the mechanisms. And communicate these so there is an ongoing discussion and we can continue to advance the field. And we need to work together to do it – in a kind of system I refer to as ‘radical collaboration’. Our 2009 publication (with Becky Farley) was towards the beginning of that collaborative journey for me, which lasts to this day, as you can see from the stream of ongoing publications on this topic at the bottom of this blog. 

Question: What are the proposed neuroplasticity mechanisms and how can we implement what we know?

Hirsch: The field is still in its early infancy. In theory, exercise will do more for you than any pill. Taking a pill is not empowering. Although much more research needs to be conducted, there are probably more than 3 dozen mechanisms of exercise-induced neuroplasticity. Possible disease-modifying mechanisms underlying the effect of physical exercise on corticostriatal plasticity in human PD likely involve changes in endogenous corticostriatal levels of neurotrophins, such as BDNF that keeps neurons vibrant, healthy and alive, increased cortical activation, connectivity, reduced inflammation, modification of dysfunctional striatal brain circuitry, improved dopaminergic signaling, and increased dopamine D2 receptors. These effects can manifest in improvements both in motor and non-motor aspects of PD. As a first step toward promoting greater international collaboration and knowledge on exercise-induced neuroplasticity in human PD, we need to start working together in radical ways – a system I call ‘radical collaboration’. Scientists and clinicians are already collaborating all around the world and some are collaborating with people with PD but so far our efforts have not been very productive. We need a radical shift in our collaboration-ability, away from competing with each other for grants and funding, towards a unified partnership approach where all the stakeholders benefit, including the health of our planet. Big questions cannot be solved by individuals. It requires teams. Working together. Anyone who knows anything about science knows this. The problem is, we have become addicted to funding, and scientists are not the best collaborators or team players, so I think there are new skills we must learn. So in that sense, we need a radical shift.  To become advocates for each other and for the sake of our tiny blue planet, to promote a health-enhancing, vibrant earth.

Question: How important is exercise to PD?

Hirsch: Anyone planning to begin exercise should consult with a healthcare professional (physician, physical therapist) to ensure there are no contraindications. The exercise and PD animal data suggests that individuals with PD should begin exercising the day they are diagnosed.  The American Medical Association launched a new educational initiative they call “Exercise is Medicine.” The aim of this initiative is to encourage healthcare professionals to talk to their patients about exercise at every office visit and to support patients in making healthy lifestyle choices.  Physicians and physiotherapists should help their patients find places in the community to exercise. Research suggests that patients value their physicians advice, although patients don’t always follow it, and communities may not be offering exercise programs specific to PD, so there is still a disconnect between physician’s giving good advice and then patients actually finding places to exercise and sticking with it.  In truth, we don’t yet understand what motivates people with PD to begin exercise or the factors that encourage them to keep exercising for a lifetime.  But, if healthcare professionals are not talking to their patients about exercise and there are no community programs catering to patients’ individual needs, which may turn out to be the typical situation, we should not be surprised that patients are not as physically active as they could be. It is hoped that our paper and hopefully my presentation on the proposed mechanisms of exercise induced neuroplasticity in human PD in Barcelona at the WPC 2023 gives physiotherapists, patients and physicians something to talk about!

Question: So, if exercise is important, what should people with PD do to get it?

Hirsch: Get active, in any way you can - at home, in your neighborhood, community and city. Talk to your doctor or seek the advice of a physiotherapist specializing in Parkinson’s care.  Many individuals in the early stages of Parkinson’s might believe they don’t need exercise and might choose to avoid the subject; These individuals may lack awareness that they have deficits because, in the early stages of PD, these can be subtle and difficult to detect and therefore individuals may put off going to their doctor; many physicians and therapists are still unaware of neuroplasticity-based exercise principles so they might not be aware that individuals at all stages of PD can benefit from exercise and therapy; and the exercises individuals may be doing on their own or receiving from PTs may not be as efficacious as they could be; and our environment (pollution) may be acting against the endogenous release of neurotrophins, such as brain derived neurotrophic factor as research has shown that for example in situations where we cycle near busy streets, endogenous BDNF becomes down regulated; and exposure to environmental toxins, such as pesticides or solvents might be responsible, in large part, to mood and mental changes that make exercise more difficult. The good thing is that if exposure to environmental toxins is important, there is a lot we can do by eliminating these chemicals and substances from our environment. And it might even be that exercise confers neuro-protection or neuro-restoration in people with probably neurotoxin-induced Parkinson’s disease, but those studies still need to be conducted. So for now it is important for people with PD to be discussing these things with their healthcare providers and also to advocate for change to a healthier, wellness enhancing planet earth on a global level.  People with PD who receive ineffective treatment – treatments that are not neuroprotective or neurorestorative or do not affect the signs and symptoms may stop exercising altogether, which is stressful, and we know from the animal literature that being sedentary or being exposed to stress may be pro-degenerative for the Parkinson’s brain. Again, making an appointment with a physician or a PT is one of the most important decisions a person can make for their overall health and for getting them involved with exercise and lifestyle changes. 

Dr. Hirsch’s research has focused on PD and the effect of high-intensity exercise in improving the cardinal signs and symptoms of the disease (i.e., postural control, fall prevention). His current research focuses on the neuroplastic mechanisms that link neurotrophic factor expression levels, physical exercise and social networks, mostly in Parkinson’s disease, and applying these insights to the clinic in the context of physical medicine and rehabilitation. Dr. Hirsch has made seminal scientific contributions in the area of exercise and Parkinson’s disease, which has provided great insights into the importance of exercise and physical activity promotion as a clinical first line treatment for Parkinson’s disease. Dr. Hirsch is also known for his pioneering work in the area of Parkinson patient/provider/scientist collaboration.

His work on physical activity promotion and brain neurotrophins has been critical in the field of neurorehabilitation. He was appointed Fellow of the American Congress of Rehabilitation Medicine and is Past Chair of the Board of Directors of the Parkinson Association of the Carolinas, past Chair of ACRM- Neurodegenerative Diseases Networking Group, Co-Chair the ACRM Committee on Diversity, Equity and Inclusion (2020-), and member of several international editorial boards. Hirsch works with researchers internationally (The Netherlands, Italy, Switzerland) and has published over 100 papers in peer reviewed international journals. Current efforts involve translating what has been learned from studies on exercise and PD neuroplasticity mechanisms to the level of the community.

Further reading:
van Wegen E, Hirsch MA, van de Berg WDJ, Rietberg MB, Vriend C, Newman M, Vanbellingen T, van den Heuvel OA. High intensity interval cycle ergometer training in Parkinson's disease: Protocol for identifying individual response patterns using a single subject research design. Front Neurol. 22 October 2020, Volume 11. https://doi.org/10.3389/FNEUR.2020.569880

Hirsch MA, van Wegen EEH, Newman MA, Heyn PC. Exercise-induced increase in brain-derived neurotrophic factor in human Parkinson's disease: A systematic review and meta-analysis. Translational Neurodegeneration. 2018;7:Article 7. DOI : 10.1186/s40035-018-0112-1. This open access paper was accessed over 10K times since publication in 2018.

Hirsch MA, Iyer S, Sanjak M.  Exercise-induced neuroplasticity in human Parkinson's disease: What is the evidence telling us? Parkinsonism and Related Disorders. 2016 Jan;22 Suppl 1:S78-81.

Mougeot JL, Hirsch MA, Stevens CB, Mougeot F. Oral biomarkers in exercise-induced neuroplasticity in Parkinson's disease. Oral Diseases. 2016 Feb 15. doi: 10.1111/odi.12463.

Heyn PC, Hirsch MA, York MK, Backus D.  Physical activity recommendations for the aging brain: A clinician-patient guide. Archives of Physical Medicine and Rehabilitation. 2016;97:1045-7.

van Wegen EEH, Hirsch MA, Huiskamp M, Kwakkel G.  Harnessing cueing training for neuroplasticity in Parkinson's disease.  Topics in Geriatric Rehabilitation.  2014;30(1):46-57.

Hirsch MA, Farley BG. Exercise, neuroplasticity and Parkinson’s disease. European Journal of Physical and Rehabilitation Medicine. 2009 Jun;45(2):215-29.

Mark A. Hirsch, PhD, FACRM is a professor at the Wake Forest University, School of Medicine, Department of Orthopedic Surgery and Rehabilitation, Winston-Salem, North Carolina, USA; Director Parkinson and Movement Disorders Lab, Carolinas Rehabilitation, and Director of Department of Physical Medicine and Rehabilitation Residency Research Education Program, Charlotte, North Carolina. He will be presenting at the WPC 2023 in Barcelona on the subject of “Biological brain changes observed following exercise in Parkinson’s: What do they tell us?” View the Scientific Program here. Twitter: @MarkAHirsch

Ideas and opinions expressed in this post reflect that of the author(s) solely. They do not necessarily reflect the opinions or positions of the World Parkinson Coalition®