Parkinson’s disease (PD) is a degenerative nerve condition that affects movement and cognition and usually worsens over time. Deep brain stimulation (DBS) of the brain structure that controls movement, the subthalamic nucleus (STN), has been shown to improve movement in people with PD, and a new study suggests that DBS at low frequencies can also improve cognitive function in those with PD.

The finding provides direct evidence that there is a connection between the brain’s cognitive center in the frontal cortex (FC) and the STN. It is rare to find a new connection in the human brain, Nandakumar Narayanan, senior author on the study, said, adding that although the existence of this connection has been discussed for years, “This is the first time we’ve experimentally shown it exists and functions in people.”

The findings are promising implications for improving cognition in those with other psychiatric or neurologic conditions, not just PD, the authors said. “It is exciting to potentially be able to improve cognition in a way that is life-changing for patients,” Jeremy Greenlee, corresponding author on the study, told TheDoctor.

Greenlee, a neurosurgeon at the University of Iowa, was able to “listen in” on brain activity during surgery to implant DBS devices in Parkinson's patients. During this procedure, recording electrodes are used to accurately place the DBS device. These electrodes also allowed doctors to record patients' brain activity without additional risk.

Patients remain awake during the surgery, and doctors had them perform a simple cognitive task while they recorded electrical activity from the parts of the brain connected to the electrodes. Listening to neural activity while patients performed the task made it possible for doctors to map the connection between the FC and the STN.

Once the FC-STN connection was established, the researchers studied the effect of low-frequency stimulation of the STN on cognitive function. During post-surgical follow-up visits, the researchers had patients estimate the passage of an interval of time with the DBS stimulator set to one of three settings: high frequency (normal for controlling movement), low frequency (4-Hz), or no frequency. Only the 4-Hz frequency improved performance on the interval timing test.

The result appeared connected to the team's earlier finding that suggested people with PD doing the timing task are missing a brain wave known as the delta wave in their FC. The delta wave cycles at a frequency of about 4-Hz.

So by stimulating the STN at 4-Hz, the delta wave in the FC, and thus cortical function, is restored, said Narayanan. When cortical function is restored, cognitive function can improve.

“The fact we are able to test a lot of our ideas from rodent studies about how neural networks work in living, awake human beings is something I never dreamed I’d be able to do, but it allows us to ask questions that might help a lot of people.”

The study is published in Brain.

—Charlotte LoBuono