Schizophrenia diagnosis and anterior hippocampal volume make separate contributions to sensory gating

Abstract

Impaired P50 gating is thought to reflect a core deficit in schizophrenia, but the relevant neural network is not well understood. The present study used EEG and MEG to assess sensory gating and volumetric MRI to measure hippocampal volume to investigate relationships between them in 22 normal controls and 22 patients with schizophrenia. In the schizophrenia group, anterior but not posterior hippocampal volume was smaller, and both the P50 and M50 gating ratios were larger (worse) than in controls. Independent of group, left-hemisphere M50 gating ratio correlated negatively with left anterior hippocampal volume, and right-hemisphere M50 gating ratio correlated negatively with right anterior hippocampal volume. Schizophrenia diagnosis predicted M50 gating independent of hippocampal volume. These results are consistent with the finding that hippocampus is a critical part of a fronto-temporal circuit involved in auditory gating. Copyright © 2008 Society for Psychophysiological ResearchAddress reprint requests to: Robert J. Thoma Hippocampal structure and function are abnormal in schizophrenia (for recent reviews, see Goldman & Mitchell, 2004;Harrison, 2004). The most conspicuous functional abnormalities associated with hippocampal damage are deficits in learning and memory (especially relational mnemonic ability; Cohen & Eichenbaum, 1993;Moses, Cole, Driscoll, & Ryan, 2005;Rudy & Sutherland, 1995;Rudy & Sutherland, 1989). However, hippocampus is also known to subserve cognition in other ways. For example, there is evidence that hippocampus serves as part of neural networks involved in novelty detection (Knight, 1996;Moses & Ryan, 2006), in orienting attention toward novel auditory stimuli (Knight, 1996), and in novel target detection in tasks such as dichotic listening (Pollmann, Lepsien, Hugdahl, & von Cramon, 2004) and the oddball paradigm (Crottaz-Herbette, Lau, Glover, & Menon, 2005;Paller, McCarthy, Roessler, Allison, & Wood, 1992;Tesche, Karhu, & Tissari, 1996). Hippocampus is also known to be critical for the gating of sensory responses to stimuli. It has been well established that hippocampus is involved in prepulse inhibition (PPI) of startle, sometimes known as sensorimotor gating (Bast & Feldon, 2003;Caine, Geyer, & Swerdlow, 1992;Swerdlow et al., 2001;Zhang, Bast, & Feldon, 2002a, 2002b. However, whether and how hippocampus is involved in gating of the auditory event-related brain potential (ERP) P50 component in a paired-click paradigm is an open question.Impaired P50 sensory gating has been described as the most robust physiological finding in schizophrenia research (Bramon, Rabe-Hesketh, Sham, Murray, & Frangou, 2004;Heinrichs, 2004) and is associated with sensory overload and disruption of higher-order cognitive processing. Gating is typically assessed in a paired-click paradigm, in which two identical click stimuli are played in succession and the P50 response following each is measured. Normally, individuals show a reduced P50 response following the second click, and this reduction of the ...

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COMT Val108/158Met genotype modulates human sensory gating

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