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Last modified: Monday, September 17, 2012

IU researchers receive $1.9 million grant to study role of 'lesser brain' in schizophrenia

Researchers to use advanced research methods to study brain abnormalities in people with schizophrenia, their close relatives

Sept. 17, 2012

BLOOMINGTON, Ind. -- A team of Indiana University researchers led by William P. Hetrick, chair of the Department of Psychological and Brain Sciences at IU Bloomington, has received a $1.9 million award from the National Institute of Mental Health to study the neurobiological basis of schizophrenia, a devastating psychological disorder affecting approximately 2.4 million U.S. adults.

William Hetrick

William P. Hetrick

The five-year study, which builds on findings from a previous five-year NIMH grant spearheaded by Hetrick, will examine the structural and functional integrity of the cerebellum, a critical but understudied region of the human brain. Long thought to be exclusively involved in balance and coordination of body movements, in recent years this "lesser brain" has been found to play a significant role in mental processes. Abnormalities in the cerebellum have also been found in several mental illnesses. This study will explore the role of the cerebellum in schizophrenia.

Members of the research team include Olaf Sporns, Aina Puce, Dae-Jin Kim, Brian O'Donnell, Amanda Bolbecker and Sharlene Newman, all from the College of Arts and Sciences' Department of Psychological and Brain Sciences; and Alan Breier from the IU School of Medicine's Department of Psychiatry.

"Our initial research points to a fundamental disturbance in the function of the cerebellum in not only individuals diagnosed with schizophrenia but also in individuals at risk for developing the disorder, such as close family members and individuals showing sub-clinical symptoms," Hetrick said. "Our neuroanatomical, functional and behavioral findings are converging to suggest that cerebellar abnormalities are associated with, and may contribute to, cognitive and clinical symptoms of schizophrenia; testing this hypothesis is the innovative focus of this project."

The over-arching goals of the study are to use functional and structural magnetic resonance imaging to examine whether abnormalities in the cerebellum, as well as its connectivity to other brain areas, are present in individuals with schizophrenia and their first-degree relatives. MRI will be collected when the participants are at rest and when they are engaged in several cerebellar-based tasks, including eyeblink conditioning, tone-paced repetitive finger tapping, and time bisection estimation. Cutting-edge methods including connectome network science analyses and dynamic causal modeling will be used to analyze task-related fMRI activation and resting state fMRI. Diffusion tensor imaging tractography will determine brain white matter connectivity of the cerebellum to cortical brain areas. These techniques will determine the direction of connectivity to rule out models in which the origin of the observed deficits lies in non-cerebellar regions of the brain.

Hetrick and colleagues hypothesize that people with schizophrenia will be impaired on the cerebellar-based tasks, that they will show cerebellar abnormalities on functional and structural MRI, and that the connections of the cerebellum to other brain regions will be deviant compared to people without a psychiatric illness. The team also predicts that relatives will show a profile of abnormalities parallel to those seen in schizophrenia.

Hetrick and colleagues believe the data from this project will critically inform models of cerebellar involvement in cortical cognitive processing in psychiatric illness and yield insights about potential novel mechanisms of illness and targets of treatment.

Hetrick's hunch is that they will learn "that the 'lesser brain' plays a much bigger role in schizophrenia than previously thought and may be an important target for treatment."