Increased Hippocampal, Thalamic, and Prefrontal Hemodynamic Response to an Urban Noise Stimulus in Schizophrenia

Objective: People with schizophrenia often have difficulty ignoring unimportant noises in the environment. While experimental measures of sensory gating have yielded insight into neurobiological mechanisms related to this deficit, the degree to which these measures reflect the real-world experience of people with schizophrenia is unknown. The goal of this study was to develop a clinically relevant sensory gating paradigm and to assess differences in brain hemodynamic responses during the task in schizophrenia. Method: Thirty-five participants, including 18 outpatients with schizophrenia and 17 healthy comparison subjects, underwent scanning on a 3-T MR system while passively listening to an "urban white noise" stimulus, a mixture of common sounds simulating a busy urban setting, including multiple conversations and events recorded from a neighborhood gathering, music, and talk radio. P50 evoked responses from a typical paired-click sensory gating task also were measured. Results: Listening to the urban white noise stimulus produced robust activation of the auditory pathway in all participants. Activation was observed in the bilateral primary and secondary auditory cortices, medial geniculate nuclei, and inferior colliculus. Greater activation was observed in the schizophrenia patients relative to the comparison subjects in the hippocampus, thalamus, and prefrontal cortex. Higher P50 test/conditioning ratios also were observed in the schizophrenia patients. These evoked responses correlated with hemodynamic responses in the hippocampus and the prefrontal cortex. Conclusions: The finding of greater activation of the hippocampus, thalamus, and prefrontal cortex during a sensory gating task with high face validity further supports the involvement of these brain regions in gating deficits in schizophrenia. This link is strengthened by the observed correlation between evoked responses in the paired-click paradigm and hemodynamic responses in a functional MRI sensory gating paradigm.