Connectivity Changes in PPN After Exercise Tied to Motor Gains

A significant improvement in the UPDRS-III score was observed after exercise training

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A person with a microphone speaks, while a person wearing a lab coat shines a light onto an oversized brain with tissue that is floating between them.

Exercise can modify the connectivity of the brain’s pedunculopontine nucleus (PPN) with other areas of the brain in people with Parkinson’s disease and gait impairments, a study has found.

Decreases in connectivity of the PPN on the left side of the brain after exercise were associated with motor improvements that correlated with the amount of walking a person did.

“Altered PPN functional connectivity can be a marker for exercise-induced motor improvement in [Parkinson’s disease], ” the researchers wrote.

The study, “Walking exercise alters pedunculopontine nucleus connectivity in Parkinson’s disease in a dose-dependent manner,” was published in Frontiers in Neuroscience. 

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Gait disturbances are common in Parkinson’s disease and, while various approaches including physical rehabilitation, medications, or deep brain stimulation, have been evaluated, these issues remain largely untreatable, according to researchers.

The brain changes underlying gait abnormalities in Parkinson’s are not well understood, but the PPN — a component of the mesencephalic locomotor center, a brain structure critical for gait control — is thought to be involved. The PPN connects broadly with other brain regions involved in movement.

Alterations to the PPN have been previously linked to gait abnormalities in Parkinson’s patients and have emerged as a target of interest for treating gait problems, either by medication or brain stimulation.

Exercise is well recognized as a behavioral intervention that can help gait issues and has been shown to affect the functional connectivity, or degree of communication, between various brain regions. But its effects on PPN functional connectivity were not known.

The researchers investigated the impact of exercise on PPN connectivity in 27 gait-impaired Parkinson’s patients with mild to moderate disease, as determined by the Hoehn and Yahr stage I–III. Of these patients, 17 were men and 10 were women, with a mean age of 64.5.

After a month of at-home walking to determine each person’s overall pattern of activity and gait, participants began a three-month home-based walk training program, consisting of a minimum of 60 minutes of walking per week at their own pace.

Comprehensive assessments, including measures of movement, cognition and quality of life, were collected before baseline walking, before the walking training, and after the training. A functional MRI was performed before and after the training to measure PPN functional connectivity.

Before the exercise program, the degree of functional connectivity of the PPN on the left side of the brain was correlated with motor performance, as measured by the Unified Parkinson’s Disease Rating Scale motor score (UPDRS-III). A greater degree of connectivity was therefore linked to a worse motor performance.

Changes in PPN functional connectivity were observed after exercise, but differed on the left and right side of the brain. Specifically, overall functional connectivity was increased for the right PPN. In contrast, a trend towards decreased connectivity was seen on the left side.

After training, a significant improvement in the UPDRS-III score was observed, demonstrating that exercise improves motor function. Certain brain connectivity changes were linked to these improvements.

Specifically, the observed reductions in left-sided PPN connectivity after exercise were correlated with UPDRS-III improvements, whereas changes in right connectivity were not. Increases in the laterality of PPN connectivity strength were also linked to motor improvements. Laterality refers to the dominance of a particular side of the brain, rather than equal connectivity strength in both sides.

The decrease in left PPN connectivity was also correlated with the number of walks a person took.

“We demonstrated that PPN functional connectivity change is modified by walking exercise in a dose-dependent manner. The associated improvement in motor function provides additional evidence for how exercise can positively impact [Parkinson’s disease],” the research team wrote.

Given the notable differences between the PPN on the right and left side of the brain, the researchers said the result “further supports an asymmetry in PPN connectivity strength, as previously suggested.”

The inclusion of only patients with relatively mild disease and a lack of a healthy comparator group marked the study’s limitations, they said, noting that the results, nevertheless, “provide additional evidence of altered functional connectivity of the locomotor network in [Parkinson’s] patients and further support evidence of lateral PPN connectivity strength early in the disease course,” the researchers wrote.

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