Grant: Operating Grant

The brain can be subdivided into circuits that occupy its top (dorsal) and bottom (ventral) parts. This dorsal-ventral organization is manifest in the expansion of the brain's surface (cortex) across species and the maturation of the brain from infancy to adulthood. Research suggests that neurodevelopmental disorders, including Schizophrenia (SCZ), may be caused by the improper development of dorsal circuits. For example, vision is controlled by separate dorsal and ventral pathways that work closely together and SCZ has been linked to abnormalities in the dorsal visual pathway. The auditory system is organized in a similar fashion. However, whether SCZ also results in dorsal auditory pathway dysfunction is untested. This is an important step because auditory hallucinations, a prominent SCZ symptom, may arise explicitly from irregularities in this pathway. This proposal also examines the neurophysiology and neurochemistry of these problems. Specifically, activation of the dorsal auditory pathway results in prototypical brainwaves, known as gamma oscillations. In turn, gamma oscillations are controlled by a brain chemical known as GABA. Compromised gamma oscillations and GABA neurotransmission are believed to underlie many of the symptoms of SCZ. However, it is not clear whether these anomalies are related to disturbances in dorsal versus ventral circuitry. Therefore, this study will ascertain if (a) people with SCZ have dorsal auditory pathway impairment and (b) this impairment is due to deficient GABA neurotransmission and consequent disruption in gamma oscillations. Auditory performance will be measured using computerized hearing tests, while brainwaves and GABA will be measured using noninvasive, specialized neuroimaging techniques - electroencephalography and magnetic resonance spectroscopy. Defining which brain systems underlie the development of SCZ may lead to new treatments specifically targeting those brain circuits that are critical to symptom production.