Nav: Home

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 a timeframe of a few seconds is a simple but universal thinking skill in mammals. It also is an ability that is consistently impaired in patients with Parkinson's disease (PD), and for University of Iowa neurologist Nandakumar Narayanan that makes "timing" an ideal tool to study cognitive problems in PD.

Parkinson's disease is caused by loss of the brain signaling chemical dopamine and affects about 1 million people in the United States. It is most commonly thought of as a disease that causes movement problems, but neurologists now know that PD can significantly affect patients' thinking, or cognitive abilities, too.

"The cognitive problems associated with PD are very debilitating," says Narayanan, MD, PhD, UI assistant professor of neurology. "They affect quality of life by causing loss of the ability to work, nursing home placement, falls, and increased health care costs. We have a lot of great treatments for the motor symptoms of Parkinson's disease, but there is very little I can do to treat the cognitive symptoms, and that is very frustrating for me."

Working in the lab and the clinic, Narayanan and his team record brain activity in mice and humans as they do simple timing tasks. The scientists also use various genetic technologies to manipulate and study brain activity in the mice. These experiments help to reveal the neurocircuitry that controls timing ability, and explain how this simple cognitive process is disrupted by a lack of dopamine.

In a new study, published online Dec. 15 in the journal Current Biology, the researchers show for the first time that brain stimulation of specific neurons at a specific frequency can improve timing in mice that are missing dopamine. The findings imply that, at least in theory, it might be possible to use brain stimulation to improve cognitive problems caused by PD, and possibly other cognitive disorders, too.

The team studied 12 patients with PD and showed that their ability to judge a period of time (12 seconds) was much poorer than people without PD. Measurements of brain activity from the frontal cortex using EEG (electroencephalography) showed that PD patients were also missing a specific brain wave known as the delta wave, which cycles at a frequency of about 1-4 times per second (1-4 Hertz), while they were doing the timing task.

As expected, mice that lacked dopamine in their frontal cortex also performed poorly on a timing task. However, the team was excited to discover that the animals were also missing the delta rhythm, suggesting that this specific, dopamine-dependent neural signal might be important for timing abilities.

In the frontal cortex, dopamine normally activates neurons with D1 dopamine receptors. The UI team, including Young-Cho Kim, PhD, first author on the study and a postdoctoral fellow in Narayanan's lab, genetically altered the mice so that the D1 neurons could be artificially activated using pulses of light. When the researchers pulsed the light at the same frequency as the missing delta wave signal -- 2 Hertz -- the mice recovered their ability to perform the timing task.

"This was jaw-dropping," Narayanan says. "For the first time we are able to deliver brain stimulation to improve a cognitive behavior.

"When we stimulated D1 neurons in normal mice, we did not improve their timing'" he adds. "But in mice that have cognitive (timing) impairment due to loss of dopamine, we can make those mice better. The results suggest that, theoretically, delivering targeted, selective, and specific brain stimulation might improve some of the cognitive aspects of losing dopamine in Parkinson's disease."

Brain stimulation is already used to treat some patients with PD, but the therapy targets specific areas of the brain that are important for motor control (not the frontal cortex) and only improves movement problems of PD. The new findings suggest precise stimulation of specific neural networks in the cortex might also form the basis of new therapies that improve cognitive processes that depend on dopamine.
-end-
In addition to Narayanan and Kim, the team included Sang-Woo Han; Stephanie Alberico; Rafael Ruggiero; and Benjamin De Corte from the Department of Neurology at the UI Carver College of Medicine; and Kuan-Hua Chen at University of California Berkeley. Narayanan is a member of the UI Pappajohn Biomedical Institute and the Aging Mind and Brain Initiative at the UI.

The research was funded in part by grants from the National Institute of Neurological Disorders and Stroke, the National Institute of Mental Health, the Brain and Behavior Foundation and The Sao Paulo Research Foundation.

University of Iowa Health Care

Related Neurons Articles:

New tool to identify and control neurons
One of the big challenges in the Neuroscience field is to understand how connections and communications trigger our behavior.
Neurons that regenerate, neurons that die
In a new study published in Neuron, investigators report on a transcription factor that they have found that can help certain neurons regenerate, while simultaneously killing others.
How neurons use crowdsourcing to make decisions
When many individual neurons collect data, how do they reach a unanimous decision?
Neurons can learn temporal patterns
Individual neurons can learn not only single responses to a particular signal, but also a series of reactions at precisely timed intervals.
A turbo engine for tracing neurons
Putting a turbo engine into an old car gives it an entirely new life -- suddenly it can go further, faster.
Brain neurons help keep track of time
Turning the theory of how the human brain perceives time on its head, a novel analysis in mice reveals that dopamine neuron activity plays a key role in judgment of time, slowing down the internal clock.
During infancy, neurons are still finding their places
Researchers have identified a large population of previously unrecognized young neurons that migrate in the human brain during the first few months of life, contributing to the expansion of the frontal lobe, a region important for social behavior and executive function.
How many types of neurons are there in the brain?
For decades, scientists have struggled to develop a comprehensive census of cell types in the brain.
Molecular body guards for neurons
In the brain, patterns of neural activity are perfectly balanced.
Engineering researchers use laser to 'weld' neurons
University of Alberta researchers have developed a method of connecting neurons, using ultrashort laser pulses -- a breakthrough technique that opens the door to new medical research and treatment opportunities.

Related Neurons Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...