Cognitive Function Can be Improved In Parkinson's Disease Patients

Highlights

• New brain connection found that could be a target for improving cognitive symptoms in Parkinson's disease
• Cognitive function in patients with Parkinson's disease (PD) can be improved with low-frequency stimulation of a deep brain region
• Stimulation of subthalamic nucleus (STN) at low frequency setting of 4 Hz improves cognitive function

Low-frequency stimulation of a deep brain region can improve cognitive function in Parkinson's disease (PD) patients, reveals a new study. // The multidisciplinary neuroscience study used a rare, intraoperative brain recordings. The study findings were published online in the journal Brain, which reveal that other cognitive diseases can also be treated with brain stimulation.

The new work was demonstrated by neurologists and neurosurgeons who worked along with the Iowa Neuroscience Institute at the University of Iowa.

The research team provides the very first evidence revealing a connection between the thinking region of the brain called the frontal cortex and a more in-depth structure called the subthalamic nucleus (STN), which controls the movement in the human brain.

The results also reveal that stimulation of the STN at low frequencies can improve PD patients performance on a simple cognitive task, which is usually disrupted by PD.

Nandakumar Narayanan, MD, Ph.D., UI assistant professor of neurology in the UI Carver College of Medicine and senior study author says that it is rare to find a new connection in the human brain.

The hyper direct pathway from the prefrontal cortex to the STN has been in existence and has been in discussion for about a decade. However, this is the first time that the research team has experimentally shown that this pathway exists and does even function in people.

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"We were also able to show that if we stimulate the STN, we change the frontal cortical activity and we think it's by this pathway, and if we stimulate the STN and change cortical activity, we can actually change behavior in a beneficial way, improving the patients' cognitive performance," added Narayanan.

About one million people in the U.S are affected by Parkinson's disease, which is a progressive neurodegenerative condition.

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In patients with PD, STN deep brain stimulation at high frequencies has already been approved to treat movement problems. Apart from causing movement problems, thinking is also affected by PD.

The new findings suggest that deep brain stimulation of STN at a lower frequency can improve even cognitive symptoms in PD patients, and also in other neurologic and psychiatric diseases.

Listening in on the Brain Activity

To implant, these deep brain stimulation (DBS) electrodes in PD patients, the research team during surgeries mapped the STN-cortex connection by "listening in" on brain activity.

Jeremy Greenlee, MD, a UI neurosurgeon performs more than 30 such surgeries every year and is an expert at the mapping experiment.

To accurately place the DBS device inside the patient’s brain, Greenlee uses specialized recording electrodes to listen in on the brain activity. For experimental purposes, these electrodes allow direct recording of the brain activity in PD patients without increasing any risk during surgery.

Greenlee and his UI colleagues have a long history of expertise in using this kind of intraoperative technique, which is not commonly used.

During the surgery, patients with PD performed simple cognitive tasks to stimulate a part of the brain and electrical activity from other parts of the brain was recorded from the ones that were connected.

The research team listened to the neural activity while PD patients performed the task, which enabled them to map the connection.

The research team was able to stimulate a response to show the functional connection. The swift response shows a single, direct synaptic connection, which is why it is known as the hyper-direct pathway.

Stimulation of STN Improves Cognitive Performance

After the establishment of the existence of a hyper-direct connection, the team further investigated the effect of STN stimulation on cognitive abilities in low frequencies.

To study the cognitive decline in patients with PD and animal models of PD, Narayanan's team used a straightforward thinking task, which estimated the passage in a short interval of time accurately.

Follow up visits by the research team during post-surgery involved patients with PD carry on the interval timing task with the DBS stimulator, which was set to one of three following settings:

• High frequency (i.e., normal for controlling movement)
• No stimulation or
• A low frequency setting of 4 Hz

Only the low-frequency setting of 4 Hz stimulation has improved the performance of PD patients' on the timing test.

In previous research studies, which were from Narayanan's labs, showed that PD patients and rodent models with PD were missing a specific brain wave called as the delta wave in their frontal cortex at a frequency of about 4 Hz while doing the timing task.

Narayanan said that while STN is stimulated at 4 Hz, the delta wave was found to be restored in the mid-frontal cortex and can rescue cortical activity, which has been disrupted in PD patients improving the cognitive behavior of the patients.

The research team said that the frequencies act like communication channels between networks.

If two networks are working together at the same frequency, that might be a unique way that the networks interact and the information is transmitted.

"The fact that we can test a lot of our ideas (that come from the rodent studies) about how the neural networks work in awake behaving humans, is something I never dreamed I'd be able to do, but it enables us to ask questions that might actually help a lot of people," Narayanan says.

Greenlee adds that it is exciting to have a way to improve cognition, which could be life-changing for PD patients.

Reference

1. Ryan Kelley, Oliver Flouty, Eric B Emmons, et al. A human prefrontal-subthalamic circuit for cognitive control. Brain (2017). DOI:10.1093/brain/awx300

Source-Medindia