Several studies have come out recently touting unconventional methods to treat Parkinson’s disease. Parkinson’s is caused by damage to neurons in the substantia nigra (SN), a region of the basal ganglia that is responsible for creating much of the brain’s dopmaine. Dopamine is an essential neurotransmitter implicated in a variety of behavioral and motivational mechanisms, and it is most notably involved in reward and addiction. However, it is also a key component of the motor system. Feedback loops from the cortex to the basal ganglia circulate information about whether to initiate or inhibit a movement, and these cicuits are greased by dopamine, activating the excitatory loop and suppressing the inhibitory one. Without adequate dopamine, the system comes to a stalemate, making the initiation of movement much more difficult and causing the hesitation, trembling, and inertia that are characteristic of Parkinson’s.
Common treatments for Parkinson’s include flooding the brain with dopamine agonists or the dopamine precursor L-DOPA. This boosts dopamine levels in the brain, causing the remaining healthy SN neurons to produce and fire greater amounts of the neurochemical, making up for the deficit from the impairment of the other cells. However, there are currently no treatments that prevent the progressive cell death in the SN, and in advanced stages it is difficult to compensate for the abundant cell loss. Excess “artificial” dopamine in the brain can also result in the downregulation of other dopamine-producing and receiving cells, the brain adjusting to the new flood of dopamine by reducing its endogenous production and receptor sensitivity in an attempt to return to a dopaminergic homeostasis. Additionally, it is impossible to localize dopamine agonists to the motor regions of the brain, meaning that many Parkinson’s patients treated with dopamine come to display symptoms similar to those seen in impulse control disorders, which are also commonly rooted in a widespread dysregulated dopamine system. These can include the development of compulsive gambling and shopping problems, sexually deviant behavior, and drug addiction.
Given the obvious shortcomings in the current treatment options, the need for alternative therapies for Parkinson’s is widely acknowledged. Two labs taking on this problem have recently published results on alternative treatments that do not involve pharmacological challenge and instead target a patient’s motor efficacy, one increasing the patient’s control and the other withdrawing it.
The first, published in the Journal of Neuroscience, suggests that self-regulation of brain activity facilitated by real-time fMRI feedback can increase brain activation and decrease Parkinson’s symptoms. Focusing on the supplementary motor region, an area of cortex that has direct connections with basal ganglia pathways and that is commonly shown to have diminished activity in Parkinson’s, researchers at the University of Cardiff had patients mentally activate this region using motor imagery while in the fMRI scanner. Patients in the experiment group received direct feedback on their activation levels during the trials via a thermometer display, whereas those in the control group did not have any indication of their success at mentally activating the area. The patients who received the real-time feedback were able to activate the supplementary motor region to a greater extent than those who did not, successfully upregulating this area as well as other brain regions associated with the motor system. They also significantly improved their ability on a motor function test and a subjective assessment of Parkinson’s symptoms, whereas control participants did not. Researchers speculate that this increase in activity and subsequent improvement in symptoms is due to a greater excitation of compensatory motor pathways, strengthening these connections and facilitating the activity of the under-utilized basal ganglia circuitry.
The second method, published in Exercise and Sport Sciences Reviews, takes an alternative approach, deliberately taking the control out of the hands (or legs) of the participants. Researchers at the Cleveland Clinic in Ohio are investigating the idea that forced exercise, with exertion levels out of the patient’s control, can be more effective in treating Parkinson’s symptoms than voluntary physical activity. Led by Dr. Jay Alberts, researchers had patients ride on the back of tandem bicycles where the energy output was set at 50% higher than the patients’ comfortable self-selected effort levels. After eight weeks at the greater energy expenditure, patients had a significant decrease in tremors and other motor symptoms, which lasted for approximately one month after treatment was stopped. Additionally, the benefits seen were not just a result of localized increased muscle tone or coordination as has been the case in previous studies investigating the effects of exercise in Parkinson’s. Instead, participants showed improvements in movement throughout the body, as well as increased neural activity during MRI scans of the basal ganglia and cortex. Researchers are as yet unsure of the basis for these improvements, though the emotional and cognitive benefits of exercise are widely known. In an interview with the New York Times, Dr. Alberts speculated that the effects could stem from the release of stress hormones during exercise, which can trigger the neurochemical systems and are more active during forced or very high intensity activities than comfortable voluntary levels of exertion.
While these studies are still only addressing the symptoms rather than the root of the problem, they do provide new evidence for treatment options beyond the standard fair. Importantly, neither of these methods comes with any of the adverse side effects of dopaminergic treatments, which can severely undermine the efficacy and quality of life improvements for patients with Parkinson’s disease. Further research is of course always needed, and certainly these methods would need to be used in tandem with current drug therapies, but these studies present an interesting alternative to complete reliance on pharmacological medication to treat the symptoms of neurological disorders.