Visual Masking as a Probe for Abnormal Gamma Range Activity in Schizophrenia Michael Foster Green, Jim Mintz, Dustin Salveson, Keith H. Nuechterlein, Bruno Breitmeyer, Gregory A. Light, and David L. Braff Background: Visual masking procedures assess very early stages of visual perception. Patients with schizo- phrenia consistently show deficits on visual masking tasks, and these deficits likely reflect vulnerability to schizophre- nia. We conducted two experiments to determine whether visual masking procedures can reveal underlying abnor- malities in gamma range oscillations in schizophrenia. Methods: In the first experiment, we conducted nonlinear modeling of visual masking performance data from 89 male schizophrenic patients and 20 male comparison subjects. In the second experiment, electrophysiological recordings of event-related gamma activity were taken during a visual masking task in a subset of eight patients and seven control subjects. Results: In the first experiment, nonlinear modeling of the performance data revealed evidence of oscillations in the gamma range (30 and 35 Hz) for the comparison group but not patients. In the second experiment, the comparison group, but not the patients, showed a burst of gamma range activity 200 – 400 msec following target presenta- tion. The difference between patients and comparison subjects in this time period was significant (p  .05). Conclusions: Visual masking procedures can serve as a probe for underlying gamma range activity, which ap- pears to be aberrant in schizophrenia. Perceptual prob- lems in schizophrenia may, at least in part, be due to a failure to establish and/or maintain gamma range oscil- lations. Biol Psychiatry 2003;53:1113–1119 © 2003 So- ciety of Biological Psychiatry Key Words: Schizophrenia, visual masking, gamma fre- quency, backward masking, visual processing, neurocog- nition Introduction S chizophrenia is associated with a wide range of per- ceptual problems. Early visual processing in schizo- phrenia is often assessed with visual masking techniques. In visual masking, the visibility of a briefly presented target is reduced by a mask that is presented very shortly before or after the target (Breitmeyer 1984, 1992). When the mask follows the target, the effect is called backward masking. Schizophrenic patients consistently show back- ward masking performance deficits (i.e., they require a longer interval between target and mask to identify the target) compared with nonclinical subjects (Braff et al 1991; Cadenhead et al 1998; Green and Walker 1986; Rund 1993; Saccuzzo and Braff 1981; Schwartz et al 1983; Slaghuis and Bakker 1995). These deficits appear to reflect vulnerability factors for schizophrenia, as opposed to the symptoms of the illness, because remitted, unmedi- cated patients and unaffected siblings show similar deficits (Green et al 1997, 1999; Keri et al 2001; Miller et al 1979); however, the results may depend on the difficulty level of the test, because one study using a relatively easy version of backward masking did not find deficits in a high-risk sample of adolescents (Lieb et al 1996). In an influential model of the neural basis of backward masking, Breitmeyer and Ganz (1976) have proposed that masking depends on the interactions of transient (magno- cellular) and sustained (parvocellular) visual systems (Breitmeyer and Ganz 1976; Breitmeyer 1984). The model proposes that these visual channels travel in parallel until they start to interact at the level of the primary visual cortex. Backward masking occurs when the transient channels of the mask interfere with the sustained channels of the target. The sustained channels process high spatial frequency information and are needed for identification of the target. This model has recently been expanded to take into account recent developments in neuroscience. Ac- cording to the expanded version of this model (Pu- rushothaman et al 2000), the sustained visual channels oscillate in the gamma range (Breitmeyer and Ogmen 2000). Depending on whether the onset of the mask occurs in the peak or trough of the oscillation, it will have more From the Departments of Psychiatry and Biobehavioral Sciences (MFG, JM, KHN) and Psychology (KHN), University of California, Los Angeles, and Veterans Affairs Greater Los Angeles Healthcare System (MFG, JM, DS), Los Angeles, California; Department of Psychology (BB), University of Houston, Houston, Texas; and Department of Psychiatry (GAL, DLB), University of California, San Diego, La Jolla, California. Address reprint requests to Michael F. Green, Ph.D., UCLA, Neuropsychiatric Institute, 760 Westwood Plaza, C9-420, Los Angeles, CA 90024-1759. Received April 24, 2002; revised August 21, 2002; accepted October 2, 2002. © 2003 Society of Biological Psychiatry 0006-3223/03/$30.00 doi:10.1016/S0006-3223(02)01813-9