Can we predict motor learning sequence?
A look at motor learning in Parkinson’s Disease
INTRODUCTION TO PARKINSON’S DISEASE
Physical therapists are commonly involved in the treatment of neurodegenerative disorders, and Parkinson’s disease is the prototypical example in older patients. As a matter of fact, in Africa, Parkinson’s Disease (PD) is occurring more frequently than in the past. Many possible reasons exist, including better diagnostic techniques, increasing exposure to causative factors, and an increasing aging population.
As such, it is important to pay attention to secular trends in our treatment population. Though they can occur in younger age groups, the presence of PD and dementia in the senior group is a growing concern globally.
PD is characterized by a reduction in dopamine-producing cells of the substancia nigra. Thus the nigrostriatal pathways of the basal ganglia are starved of dopamine, and this leads to a variety of movement disorders such as motor tremors, bradykinesia (slowness of movement), rigidity, motor fluctuations, and other disorders. The most serious long-term effects are seen in gait and balance disorders and these ultimately lead to activity restriction and dependency. PD patients suffer from freezing during ambulation, as well as a festinating gait (described as inability stopping), and overall postural instability. However, PD is much more complex. Patients may also suffer from autonomic disturbances, that may lead to swallowing difficulties for example. They may also suffer from cognitive disorders which are the result of involvement of other areas of the brain, but these are less fully understood. In addition, a person with PD (i.e. PwPD) suffers from the general clinical picture of someone with a chronic condition, and this can include mental health issues like lack of motivation, depression, dementia, and others.
Treatment of PD requires a multidisciplinary approach. This involves both rehabilitation and medical personnel. The gold standard treatment is levodopa or L-dopa. It is a form of inactive dopamine that is ingested daily by PwPD. One of its advantages is that it is not transformed into its active form until it crosses the blood brain barrier (BBB). Most studies report that L-dopa reaches its peak plasma concentration about one hour after ingestion. Thus most studies describe a state of ON and OFF, referring to levodopa effect during treatment sessions.
Unfortunately, over time, the nigrostriatal pathways develop a tolerance to levodopa. When this happens, the addition of carbidopa becomes necessary to reduce the effects of tolerance and improve levodopa’s efficacy. Patients also take many other dopamine agonists. So sometimes, the ON / OFF description is not totally correct because of the presence of these other drugs, which may affect the treatment session, however mildly.
Finally, we should mention the ongoing hypothesis of a levodopa overdose. Some current studies have found reduced learning while ON levodopa, suggesting that levodopa dosing may affect motor performance adversely and have suggested investigating this phenomenon. The physiologic explanation is that in the normal aging process, loss of dopamine-producing cells occurs. However, the cells of the anterior tegmentum are affected in this situation, and these cells provide dopamine to the mesocorticolimbic tracts, which are association tracts between the basal ganglia and subcortical areas. The explanation of the overdosing becomes clear. The levodopa dose that is given to patients not only provides dopamine to the nigrostriatal but also to other dopaminergic nerve tracts of the mesocorticolimbic system, which in PD are not affected. The ongoing hypothesis states that overdosing in these tracts leads to a reduction of some forms of motor learning, specifically general motor learning.
MOTOR THEORIES
In spite of all the treatments available for PD, patients’ movements will eventually deteriorate and physical therapy becomes the only recourse for them.
A common goal in physical therapy is improving motor performance. Motor performance is a reflection of motor skill acquisition, i.e., motor learning. Thus, we can expect beneficial outcomes from physical therapy only in cases where motor learning can occur.
In the past, the Schema theory was the eminent theory explaining motor control and learning as well as the basis of most of our understanding of motor function. While it is beyond the scope of this short review to go into detail, we can mention that Schema introduced the relationship between learning and variables like repetition, training, and feedback. Most importantly it introduced motor programs into our vernacular. This was a “great leap” which transported our understanding of movement from basic reflex responses to complex programs controlled by higher centers. But Schema wasn’t perfect, and it didn’t account for movement variability nor did it explain the non-linear nature of learning. Thus, about 20 years ago, interest in thermodynamics led to the emergence of a new theory called Dynamic Systems Theory (DST), which posed a serious threat to Schema. By observing weather systems, physicists and weather experts were able to explain some of the predictability in nature, but they also understood that weather systems affected each other, thus there was degree of variability that was impossible to detect. This is what DTS offered physical therapy. It suggested that motor learning was influenced by a multitude of systems and that it was non-linear and variable. It suggested challenging multiple systems at the same time would lead to better retention and translation of therapy into the patient’s external environment. For example, dual tasks that challenge verbal memory while performance balance activities. While they seem like two different systems, the ability to remember the words as a form of general learning and the ability to perform or respond to balance perturbations is also a form of general learning, they somehow exert a synergistic effect on learning paths improving outcomes. This has been documented in many studies, but is beyond our current review of Olivier et al.’s research on predictability of learning and the effects of levodopa.
OLIVIER ET AL. STUDY ON PREDICTING MOTOR SEQUENCE OUTCOMES
Because of its progressive nature, PD presents a challenge to physical therapists. To answer some of these questions, Olivier et al. (2019) decided to look for evidence of the following:
1. Is relearning possible in PwPD?
2. Is motor learning in PD influenced by acquisition rate, practice dose (i.e. physical therapy dose) to plateau, and physical ability?
3. Does levodopa influence learning?
The study was based on data from a secondary RCT at Utah University. Participants were pooled from local sources and had to be diagnosed with Idiopathic Parkinson’s Disease, did not suffer from any cognitive dementia, were ambulatory for at least 10m without AD or assistance in OFF phase, were H&Y stages 1-3, and were not suffering from any conditions that would endanger their safety. A blinded physical therapist assessed the participants and then stratified and randomized them into two groups: ON and OFF groups (i.e., ON levodopa, OFF levodopa).
Both groups of participants were made to practice a Serial Reaction Timed Task (SRTT), which comprised a mattress with 4 arrows in front of each foot and a computer screen that would show an arrow indicating where the foot should land. The accuracy and speed were recorded. Each step measure included the response time which was composed of the reaction time (time to foot off) and response time (time till foot was placed on correct arrow on matt, about 7kg pressure). Learning was calculated as the initial response time from the assessment (taken from the average of the first six trials) – response time of the retention test (done 2 days after the end of the protocol).
The protocol involved 6 blocks per day. Each block was composed of 6 trials. Each trial was composed of 24 steps (12 repeated steps and 12 random steps). The random steps were always changed throughout the program, while the repeated steps remained the same. On average, the routine required about 1.5 hours per day for 3 days. By the end of the three days, each participant had completed 108 trials and about 2592 steps. A retention test was done 2 days after the last practice session, and another retention test was performed 7 days after the first.
The researchers then separately calculated the average learning for the repeated and random stepping exercises. They also put together a mixed regression model to represent the learning in relation to dose and plateauing. In addition, they produced models showing the relationship between acquisition time and learning, as well as personal abilities and learning for both random and repeated sequences.
The results showed that learning occurred for both random and repeated sequences. There was also an inverse correlation between level of impairment and learning, thus those with more impairment learned more than those with less impairment. Acquisition time was inversely correlated to learning, those with quick learning acquisition learned less, thus showing that even slow starters still had the capability to learn; though there was no effect on random sequences. Results also showed that plateauing did not affect learning. And finally, the trial showed that learning was influenced positively by the effect of levodopa, thus the levodopa overdose hypothesis was challenged.
In conclusion, the results suggest the importance of dosing in physical therapy, and this could possibly explain the “attractor well” described in DTS, wherein patients need to be progressed via activities like dual tasks or other challenging techniques to improve motor performance, i.e., motor learning. The fact that the second retention test showed no difference to the first retention test further validates the learning technique, and it also proves that memory in PD is still intact within the parameters explained above. Thus, these results provide strong evidence for interventions in PD.
Reference:
1 Olivier G N, Paul S S, Lohse K R, Walter C S, Schaefer S Y, Dibble L E. Predicting motor sequence learning in people with Parkinson Disease. Journal of Neurologic Physical Therapy 2019;43(1):33-41. DOI: 10.1097/NPT.0000000000000251
I hope that you enjoyed this month’s discussion. I am doing my best to increase my contributions, but finding time for my passions is getting harder.
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