Low frequency brain stimulation improves cognition in Parkinson's disease

November 28, 2017, University of Iowa
The image illustrates changes in prefrontal brain activity when the subthalamic nucleus (STN) is stimulated at: high frequencies (right head), not stimulated at all (left head), or stimulated at 4 Hz (middle head). Stimulating the STN at 4 Hz produces a significant increase in frontal activity (also at 4 Hz), which correlates with improved patient performance on a simple cognitive task that is usually disrupted by Parkinson's disease (PD). The findings by neuroscientists at the University of Iowa and published Nov. 28 in the journal Brain, suggest that low frequency stimulation of the STN may provide an approach for treating cognitive symptoms of PD, and possibly other cognitive diseases. Credit: Narayanan Lab, University of Iowa

A multidisciplinary neuroscience study using rare, intraoperative brain recordings suggests that low frequency stimulation of a deep brain region may be able to improve cognitive function in patients with Parkinson's disease (PD). The study findings, published Nov. 28 online in the journal Brain, also hint at the broader potential of brain stimulation for treating other cognitive diseases.

The new work by neurologists and neurosurgeons with the Iowa Neuroscience Institute at the University of Iowa provides the first direct evidence of a connection in the human brain between the thinking region of the brain (the ) and a deeper structure called the subthalamic nucleus (STN) that is involved in controlling movement. The study also shows that stimulation of the STN at low frequencies improves the performance of PD patients on a simple cognitive task that is usually disrupted by PD.

"It's not very often that you identify a new connection in the human brain," says Nandakumar Narayanan, MD, PhD, UI assistant professor of neurology in the UI Carver College of Medicine and senior study author. "The existence of this hyperdirect pathway from the prefrontal cortex to the STN has been bandied about for around a decade, but this is the first time we've experimentally shown that it exists and functions in people.

"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," he adds. "And if we stimulate the STN and change cortical activity, we can actually change behavior in a beneficial way, improving the patients' ."

Parkinson's disease is a progressive neurodegenerative condition that affects about one million people in the United States. Deep brain stimulation of the STN at high frequencies is already approved to treat movement problems in some patients with PD. In addition to causing movement problems, however, PD also affects thinking. The new findings raise the possibility that STN deep brain stimulation at a different (low) frequency might also improve cognitive symptoms in PD, and possibly even in other neurologic and psychiatric diseases.

Listening in on the brain

The team was able to map the STN-cortex connection by "listening in" on during surgeries to implant (DBS) electrodes in patients with PD.

UI neurosurgeon Jeremy Greenlee, MD, conducts more than 30 such surgeries every year and his expertise was vital to the mapping experiment. Using specialized recording electrodes placed inside the patients' brains, Greenlee listens in on brain activity in order to accurately place the DBS device. Those electrodes also allow direct recording of brain activity for experimental purposes in patients who are awake during the procedure without adding any risk. This kind of intraoperative recordings is not very common, but Greenlee and his UI colleagues have a long history of expertise in the technique.

During the surgery, the patients did a simple cognitive task as a way of stimulating one part of the brain while recording electrical activity from other parts that are connected. Listening to the neural activity during the task allowed the team to map the connection.

"We were able to evoke a response to show the functional connection," Greenlee explains. "The very fast response suggests a single, direct synaptic connection - that is what hyperdirect means."

Stimulation improves cognitive performance

Having established the existence of the hyperdirect connection, the researchers next investigated the effect of low frequency STN stimulation on cognitive abilities. Narayanan's team uses a very simple thinking task—accurately estimating the passage of a short interval of time—to study cognitive impairment in PD patients and animal models of PD.

During post-surgery follow up visits, the researchers had the patients do the interval timing task with the DBS stimulator set to one of three settings: high frequency (normal for controlling movement), no stimulation, or a setting of 4 Hz. Only the 4 Hz stimulation improved the patients' performance on the timing test.

Previous research from Narayanan's labs has shown that people with PD and rodent models of the disease are missing a specific wave known as the delta wave in their frontal cortex while they are doing the timing task. The delta wave cycles at a frequency of about 4 Hz.

"When we stimulate the STN at 4 Hz, the delta wave is restored in the mid frontal cortex," Narayanan says. "By stimulating the STN we can rescue cortical activity (which is disrupted in PD) and we can improve cognitive behavior."

The researchers think that the frequencies are like communication channels between networks. If two networks are working together at the same , that might be a unique way that the networks interact and information is transmitted.

"The fact that we are able to 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.

"It is exciting to potentially have a way to improve cognition that could be life changing for patients," Greenlee adds.

Explore further: Timing may be key to understanding cognitive problems in Parkinson's disease

More information: Brain (2017). DOI: 10.1093/brain/awx300

Related Stories

Timing may be key to understanding cognitive problems in Parkinson's disease

December 15, 2016
When a cheetah chases a gazelle, it's not raw speed that predicts the outcome of the contest. Instead, it's the animal that times its movements better that has the advantage. That ability to consciously guide movements over ...

Brain stimulation improves schizophrenia-like cognitive problems

March 28, 2017
"A beautiful, lobular structure," is how Krystal Parker describes the cerebellum - a brain region located at the base of the skull just above the spinal column. The cerebellum is most commonly associated with movement control, ...

Team constructs whole-brain map of electrical connections key to forming memories

November 22, 2017
A team of neuroscientists at the University of Pennsylvania has constructed the first whole-brain map of electrical connectivity in the brain based on data from nearly 300 neurosurgical patients with electrodes implanted ...

A noninvasive method for deep brain stimulation—Electrodes placed on the scalp could help patients with brain disease

June 1, 2017
Delivering an electrical current to a part of the brain involved in movement control has proven successful in treating many Parkinson's disease patients. This approach, known as deep brain stimulation, requires implanting ...

Researchers put brain training to the test

September 6, 2016
Researchers from The University of Queensland have shown for the first time that "brain training" for specific tasks can also improve broader brain performance, in findings with major implications for ageing brains.

Magnetic stimulation of the brain improved awareness of subject's own cognitive abilities

August 29, 2017
Researchers at Aalto University and the University of Helsinki have succeeded for the first time ever in affecting metacognition of a tactile working memory task by combining neural pathway imaging and magnetic stimulation ...

Recommended for you

Team seeks to create genetic map of worm's nervous system

December 10, 2018
How do you build a brain? What "rules" govern where neurons end up, how they connect to each other, and which functions they perform?

Classifying brain microglia: Which are good and which are bad?

December 6, 2018
Microglia are known to be important to brain function. The immune cells have been found to protect the brain from injury and infection and are critical during brain development, helping circuits wire properly. They also seem ...

Drawing is better than writing for memory retention

December 6, 2018
Older adults who take up drawing could enhance their memory, according to a new study.

Friend or foe? Brain area that controls social memory also triggers aggression

December 5, 2018
Columbia scientists have identified a brain region that helps tell an animal when to attack an intruder and when to accept it into its home. This brain area, called CA2, is part of the hippocampus, a larger brain structure ...

How the brain hears and fears

December 5, 2018
How is it that a sound can send a chill down your spine? By observing individual brain cells of mice, scientists at Cold Spring Harbor Laboratory (CSHL) are understanding how a sound can incite fear.

Adding new channels to the brain remote control

December 5, 2018
By enabling super-fast remote control of specific cells, light-activated proteins allow researchers to study the function of individual neurons within a large network—even an entire brain. Now one of the pioneers of 'optogenetics' ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.