Edit brain to treat Parkinson’s

U. SHEFFIELD (UK) — Removal of part of the brain could help sufferers of Parkinson’s disease regain smooth initiation of movement.

Many of the problems suffered by patients with Parkinson’s—difficulties in initiating actions, slow labored movements, and tremors—can be understood in terms of damage to control circuits in the brain responsible for habits, according to a new international study. The analysis is published online in Nature Reviews Neuroscience.

An important processing unit in the brain known as the the basal ganglia is part of two behavioral control circuit: habitual control, which directs fast, automatic movements; and voluntary goal-directed control, which is driven by a conscious appreciation of the action’s outcome, explains Peter Redgrave, professor of psychology at the University of Sheffield.

This means goal-directed movements are typically slower, require effort, and can only be done one at a time. Different regions of the basal ganglia are involved in goal-directed and habitual control. Parkinson’s disease is linked to a loss of the neurotransmitter dopamine from the regions involved in habitual control.

Many of the symptoms of Parkinson’s disease could be viewed in terms of a catastrophic loss of habits, which means patients have to rely on the goal-directed control system for everything they do.  This could explain why movements are slow, effortful, and easily interrupted.

For example, when approaching a narrow door or object, a patient with Parkinson’s disease can suddenly freeze and find it difficult to start again.  Under serial goal-directed control, (i.e., you can only think about doing one thing at a time), when the patient stops thinking about walking and starts to think about going through the door or avoiding the object, they stop walking.

At the level of the basal ganglia, the study maintains, the goal-directed and habitual-control circuits are physically separated, but downstream, they converge on shared motor systems (that is, we can do the same action either under goal-directed or habitual control).

Numerous experiments show that the loss of dopamine from the basal ganglia increases inhibitory output from the habitual control circuits.

For a patient with Parkinson’s disease to express goal-directed behavior, they have to overcome the distorting inhibitory signals from the malfunctioning part of the brain.  This may help explain why destruction of the parts of the basal ganglia responsible for habits can have a beneficial effect.

Removing the distorting inhibitory output from habitual-control circuits could make it easier for patients to express goal-directed behavior, says Redgrave.

“We hope our analysis provides a better understanding of the link between normal and abnormal functioning in the basal ganglia,” Redgrave says. “This is important because the better your understanding of normal function, the better the questions you can ask about its failings, which hopefully, will direct you towards more effective treatments.”

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