Why do some people who are diagnosed with schizophrenia experience psychosis, a disconnection from reality that can make them believe their actions are being controlled by aliens or the government?
Michigan State University scientists will use a $1.5 million, four-year grant from the National Institutes of Health to investigate and potentially identify the brain mechanisms related to this peculiar behavior.
Neuroscientist Katharine Thakkar suspects these psychotic symptoms may be related to faulty signaling between regions of the brain that are involved in producing movement and regions of the brain involved in sensation. These signals, known as corollary discharge signals, allow people to predict the sensations they will experience as a result of their actions.
A match between the predicted sensations of an action and what the person actually experiences contributes to our sense of agency. Without proper transmission of the sensory signals, individuals with schizophrenia may not understand how their movement or speech came about.
"We believe these corollary discharge signals are what allow us to know that 'I did something' versus 'someone did something to me,'" said Thakkar, assistant professor of psychology and lead investigator on the project.
"This study," she added, "may allow us to make great strides in our understanding of the specific mechanisms of these symptoms of schizophrenia that have been the trickiest to explain at the level of physiology."
Together with Eric Achtyes, a psychiatrist and medical researcher, and David Zhu, a professor and expert in radiology, Thakkar will study corollary discharge signals that are relayed through the thalamus to the cortex - connections known to be abnormal in people with schizophrenia.
Participants will perform eye movement tasks in an fMRI scanner. The oculomotor system is an ideal framework for investigating disturbed sensory signals, Thakkar said, noting that corollary discharge signals associated with eye movements have been studied in animals.
A major goal of the study is to identify a sensorimotor mechanism thought to support a subjective sense of agency in schizophrenia patients at different illness stages. Schizophrenia in the initial stages is marked by a psychotic break that can include hallucinations and delusions and often requires hospitalization. Psychotic symptoms seem to abate somewhat during the course of the illness.
But about half of all people with bipolar disorder experience psychosis as well. Because of this, the researchers will also study bipolar patients with psychosis.
Thakkar said it may turn out that the corollary discharge abnormalities aren't related to schizophrenia, per se, but instead to the psychosis experienced by both groups.
Bipolar disorder affects some 5.7 million adults in the United States, while schizophrenia affects about 2.2 million Americans.
"The immediate goal of the project is to understand the biological processes underlying the self-related disturbances that characterize psychosis," Thakkar said. "Long-term goals include using this oculomotor approach to identify novel treatment targets and to aid in early identification of people who will later experience psychotic symptoms."
Thakkar discusses the research in a recent paper titled "Oculomotor prediction: A window into the psychotic mind," published in the journal Trends in Cognitive Sciences.
"Understanding how the brain anticipates the sensory consequences of movement," the article states, "provides a powerful model for understanding how these processes could go awry in psychosis."