Krystal Parker, PhD, assistant professor of psychiatry, has received a five-year, $2.1 million grant from the National Institute of Mental Health to continue exploring the idea that the cerebellum may play a key role in cognitive function and may be targeted in diseases such as schizophrenia, autism, bipolar disorder, and Parkinson’s disease.
The project will investigate the interaction between the cerebellum and the frontal cortex, testing whether the cerebellum can be targeted therapeutically to restore cognitive function.
The frontal cortex is a region of the brain that is responsible for cognitive skills such as planning, timing, attention, and other higher-level processing. The cerebellum, located at the base of the skull, is traditionally associated with movement control, but has been shown to have a role in cognition. The cerebellum is densely connected to the cerebral cortex, giving it the ability to affect diverse cognitive networks and making it a potential target for treating diseases that affect cognitive function.
Parker’s previous work has shown that stimulating the cerebellum can restore frontal cortex activity and even improve cognitive processes in timing tasks. Her current study will further investigate these findings by taking a closer look at how the cerebellum is communicating temporal (timing) information.
Parker uses rodents to model disease behaviors that are typically seen in humans with schizophrenia. In schizophrenia, dopamine signaling in the frontal cortex is abnormal. By blocking dopamine signaling in the frontal cortex of rats, the team was able to produce schizophrenia-like timing problems in the animals.
“The really interesting part is that when we stimulated the cerebellum we were able to reinstate activity in the frontal cortex that was necessary for accurate timing,” says Parker, who also is a member of the Iowa Neuroscience Institute (INI). “That may be why cerebellar transcranial stimulation, which is currently in clinical trials, has been shown to rescue cognitive functioning in schizophrenia.”
Taking a closer look
Parker’s latest project takes a three-pronged approach:
- The research team will define the cerebellar contribution to cognition by looking into its involvement in a variety of cognitive tasks.
- The research team will also investigate how stimulating the cerebellum in rodents every day for three weeks influences the pathway connecting the cerebellum and frontal cortex. Through neuroimaging and advanced cell analyses, the team will also look for any structural changes involved in this process.
- Parker also plans to take a closer look at Purkinje cells, the large neurons found in the cerebellum, to uncover their role in cognitive processing. Parkers says the integration of information in the Purkinje cells creates signals that the frontal cortex needs in order to facilitate cognitive functioning.
The quest for new treatments
Transcranial magnetic stimulation (TMS) targeting the frontal cortex is approved as a treatment for depression and is currently used as a patient therapy in the Iowa Brain Stimulation Program. Cerebellar stimulation is still considered an experimental approach and is not approved as a treatment for any brain disorders.
Parker is currently overseeing human testing of noninvasive cerebellar stimulation at the UI in collaboration with Aaron Boes, MD, PhD, UI assistant professor of pediatrics and neurology, and a member of the INI.
“The potential is there for it to be a therapeutic pathway for many different diseases that involve cognitive function,” Parker says. “If we can figure that out in rodents, we can then use that data to guide our human clinical trials.”
Parker is collaborating with Jason Radley, PhD, John Freeman, PhD, and Vince Magnotta, PhD.