Summary: Scientists have uncovered a new understanding of levodopa-induced dyskinesia, a common side effect in Parkinson’s sufferers, revealing that the machine brain stops rather than straight causing these activities.
The research shows that morphine, an anesthetic, can destroy irregular brain activity during dyskinesia and promote long-lasting neurogenesis, helping the engine brain regain control. First clinical trials involving low-dose ketamine infusions demonstrate claim, with effects lasting month after treatment.
These observations could pave the way for more effective treatment to control Parkinson’s problems.
Important Facts:
- Motor Cortex Disconnect: Dyskinesia stems from a motor brain connect, no immediate action.
- Benefits of ketamine: ketamine prolongs neuroplasticity and disrupts irregular patterns.
- Clinical Promise: First tests show low-dose morphine benefits may last weeks after a single therapy.
Origin: University of Arizona
Researchers at the University of Arizona have gained new information about one of the most frequent complications experienced by Parkinson’s disease patients: the years-long onset of excessive movements.
Parkinson’s disease – a neurological condition of the mind that affects a woman’s movement – develops when the level of serotonin, a chemical in the brain that’s responsible for physical movements, begins to decline.
A substance called drug is given to counteract the loss of serotonin, which is later transformed into serotonin in the brain. But, long-term care with drug induces spontaneous and excessive motions known as levodopa-induced dyskinesia.  ,
A , study  , published in the journal , Brain , has  , uncovered new findings , about the nature of levodopa-induced dyskinesia and how ketamine, an anesthetic, can help address the challenging condition.  ,
Over the years, the head of a Parkinson’s person adapts to the drug therapy, which is why drug causes dyskinesia in the long term, said , Abhilasha Vishwanath, the article’s lead author and a postdoctoral research associate in the U of A , Department of Psychology.  ,
The research group found that the motor cortex, the head area responsible for controlling activity, becomes effectively “disconnected” during dyskinetic shows in the new study.
This finding challenges the commonly held notion that the motor cortex is in charge of these uncontrollable movements.
There’s probably not a direct link between motor cortical activity and these uncontrollable movements, but rather an indirect way is being generated, Vishwanath said.  ,
The researchers recorded motor cortex neurons acting in thousands of different ways.  ,
” There are about 80 billion neurons in the brain, and they hardly shut up at any point. So there are a lot of interactions between these cells that continue throughout the entire process,” Vishwanath said.  ,
The research team discovered that these neurons ‘ firing patterns had little to do with the dyskinetic movements, suggesting that there was more to it that a fundamental disconnection rather than direct causation.
” It’s like an orchestra where the conductor goes on vacation”, said , Stephen Cowen, senior author of the study and an associate professor in the Department of Psychology.  ,
Downstream neural circuits are left to spontaneously generate these problematic movements on their own, without the motor cortex properly coordinating movement.
This new understanding of dyskinesia’s underlying mechanism is complemented by the team’s findings regarding the therapeutic potential of ketamine, a common anesthetic.
The study demonstrated that ketamine could aid in the dyskinesia-related abnormal repetitive electrical patterns. This might allow the motor cortex to regain some movement control.
Ketamine works like a one-two punch, Cowen said. It initially alters these abnormal electrical patterns that are present during dyskinesia.
Then, hours or days later, ketamine triggers much slower processes that allow for changes in the connectivity and activity of brain cells over time, known as neuroplasticity, that last much longer than ketamine’s immediate effects.
What is the mechanism by which neurons can form new connections and strengthen existing ones is called neuroplasticity.
With one injection of morphine, useful results can be seen even after a few months, Vishwanath said.
In light of an ongoing Phase 2 clinical trial at the University of Alberta, where a group of researchers from the Department of Neurology are testing low doses of ketamine infusions as a treatment for dyskinesia in Parkinson’s patients, these findings have additional significance.
Early results from this trial appear promising, according to Vishwanath, with some patients reporting benefits that last for weeks following a single course of treatment.
Ketamine doses could be altered to ensure that the therapeutic effects are maintained while side effects are minimized, according to Cowen. Based on the study’s findings regarding motor cortex involvement in dyskinesia, completely new therapeutic strategies may also be developed.  ,
We might be able to treat dyskinesia more effectively in the future by better understanding the fundamental neurobiology underlying how ketamine works with these dyskinetic individuals, Cowen said.
Funding: The study received funding from National Institute of Neurological Disorders and Stroke ( grants R56 NS109608 and R01 NS122805 ) and Arizona Biomedical Research Commission ( grant ADHS18-198846 ).
About this Parkinson’s disease and neuropharmacology research news
Author: Niranjana Sahasranamam Rajalakshmi
Source: University of Arizona
Contact: Niranjana Sahasranamam Rajalakshmi – University of Arizona
Image: The image is credited to Neuroscience News
Original Research: Open access.
” Decoupling of motor cortex to movement in Parkinson’s dyskinesia rescued by sub-anaesthetic ketamine” by Abhilasha Vishwanath et al. Brain
Abstract
Decoupling of motor cortex to movement in Parkinson’s dyskinesia rescued by sub-anaesthetic ketamine
Movement control is governed by the gamma band and single-unit neural activity in the primary motor cortex ( M1 ).
This activity is disrupted in Parkinson’s disease ( PD ) and levodopa-induced dyskinesia ( LID), a debilitating consequence of dopamine replacement therapy for PD. Physiological features of LID include pathological narrowband gamma oscillations, finely tuned gamma (FTG), and altered M1 firing activity.
Since most studies characterize LID through visual scoring, little is known about the relationships between ongoing dyskinetic movements, gamma, and neuronal activity at fast ( sub-second ) and slow ( seconds ) timescales.
In animal models of PD and LID, we investigate how motor cortex activity changes with movement at different timescales. Furthermore, sub-anesthetic ketamine has emerged as a possible therapy for LID.
How ketamine may reduce LID is not fully understood. Consequently, we investigate how ketamine affects the relationship between motor cortex activity and movement.
