A new study has found that abnormal brain activity in people with schizophrenia mirrors similar irregular activity seen in animal models of the disorder. The study, led by two-time NARSAD Young Investigator Grantee Kevin Spencer, Ph.D., of Harvard Medical School, used electroencephalography (EEG) to measure a specific type of brain-wave activity called “spontaneous gamma power” in people with schizophrenia compared to  people without the illness. EEG is a non-invasive technique that can measure the activity of large populations of neurons in the brain through electrodes attached to the scalp of a human or animal.

Evidence from several studies suggests that the cognitive symptoms of schizophrenia – problems in making decisions, focusing or paying attention, and in using information immediately after learning it -- may be caused at least in part to a decrease in the activity of docking ports called NMDA receptors found on the surface of certain neurons. The receptor is named for a molecule (N-methyl-D-aspartate) that can activate it. The specific brain cells in question are called parvalbumin-expressing interneurons (also called PV cells). These inhibitory neurons, which tamp down signals from co-called excitatory neurons, are linked, in turn, to the production of gamma waves.

In past experiments, researchers have used genetic techniques in mice to disrupt the function of NMDA receptors in PV cells. The mice developed cognitive problems similar to those seen in people with schizophrenia, including deficits in working memory. The brains of these mice also showed increased spontaneous gamma activity, suggesting that a decrease in NMDA receptor function disrupts the balance between inhibitory and excitatory activity. If similar changes in gamma activity were observed in people with schizophrenia, then this activity could possibly serve as an indicator (or biomarker) of the cellular changes that underlie the disorder.

In their recent study, which was published online January 14th in JAMA Psychiatry, Dr. Spencer and colleagues, including former NARSAD Young Investigator Grantee Paul G. Nestor, Ph.D., of the University of Massachusetts, Boston, used EEG to measure gamma activity while people passively listened to a series of clicks. The researchers found that the people with schizophrenia had increased spontaneous gamma activity when listening to the clicks compared to the control participants. They also found a relationship between induced gamma power and auditory hallucination symptoms in people with schizophrenia.

This study draws a link between gamma activity in people with schizophrenia and the molecular and cellular mechanism that may cause the disorder. But there are several questions that will need to be answered before gamma activity will have clinical use as a biomarker for schizophrenia. These questions include how specific the study’s findings are to schizophrenia as opposed to other psychiatric disorders, whether gamma activity changes during the course of the disorder, and what impact medication has on this activity.

Read the abstract of this research paper.