Processing of auditory stimuli during visual attention in patients with schizophrenia

Abstract

Background: The aim of this study was to evaluate attentional functioning in patients with schizophrenia with an emphasis on automatic processes using the mismatch negativity (MMN) component of the event-related brain potential.

Methods: Participants were asked to perform a challenging visual discrimination task and simultaneously ignore auditory stimuli presented in the background. In different blocks of trials, the background was either a sequence of tones that included rare deviant tones differing in pitch or a sequence of tones that alternated regularly in pitch with occasional deviant repetitions. In a second experiment, participants were asked to actively respond to auditory deviant stimuli.

Results: Visual targets generated smaller N1, N2, and P3b deflections in patients than in control subjects, suggesting deficits in controlled attentional processes. Auditory deviant stimuli elicited an MMN that varied in scalp distribution as a function of the deviant-type (pitch vs. pattern). In patients with schizophrenia, impaired auditory discrimination was associated with altered MMN topography and reduced MMN amplitude.

Conclusions: These findings are consistent with impaired automatic processes in patients with schizophrenia, which may contribute to their difficulties in processing complex auditory sequences. The timing and scalp topography are consistent with impaired auditory pattern analysis in posterior association cortices.

Introduction

Patients with schizophrenia show impairment in a variety of cognitive functions, with prominent deficits in selective attention. They perform poorly in both visual and auditory discrimination tasks and show an attenuation of the scalp-recorded P300 response Ford et al 1992, Pritchard 1986, a component of the event-related brain potential (ERP) associated with controlled processes. Moreover, electrophysiological studies examining auditory selective attention have found impaired performance and reduced ERP amplitude to attended stimuli in schizophrenic patients Baribeau-Braun et al 1983, Michie et al 1990, Ward et al 1991, suggesting deficits in maintaining an effective selective processing strategy (Baribeau-Braun et al 1983). It has been proposed that impaired inhibitory functions play a central role in the schizophrenic attention disorder. That is, patients with schizophrenia would have more difficulty in filtering out both exteroceptive and interoceptive stimuli that are task-irrelevant to their current activity (McGhie and Chapman 1961). Consistent with the gating deficit hypothesis are the abnormal startle reflex (Braff et al 1978) and the abnormal brain responses to the second stimulus of a pair in a two-stimulus conditioning test Adler et al 1982, Boutros et al 1993, Freedman et al 1991. When two stimuli are presented successively and rapidly, normal adults show an attenuation of the P50 component (i.e., a positive deflection peaking at 50 msec poststimulus) to the second stimulus. Patients with schizophrenia do not show this typical P50 reduction. The lack of P50 suppression is thought to reflect an impairment in inhibitory mechanisms at the sensory level Adler et al 1982, Braff and Geyer 1990, Freedman et al 1991, similar to those seen in patients with prefrontal damage Alho et al 1994, Knight 1994. Deficits in inhibitory functioning might allow stimuli to “flood in” and perturb the perception and representations of auditory inputs, especially in conditions requiring some stimuli to be ignored.

The mismatch negativity (MMN) of human ERPs provides a neurophysiological index of early sensory and pattern analysis. The MMN is elicited by deviant stimuli embedded in sequences of homogeneous stimuli even when the stimuli are unattended (e.g., subjects engaged in a primary task such as reading). The deviant sounds may differ from the standard sounds in pitch, duration, intensity, or spatial location (for a review see Näätänen 1992). Deviations from simple auditory patterns, such as occasional repetitions occurring in a sequence of tones that alternate regularly in pitch Alain et al 1994, Nordby et al 1988, also generate an MMN wave. The MMN is isolated by the difference wave between the standard and deviant tones and peaks at a latency of 140–240 msec poststimulus over midline frontal areas. It reflects a neural mismatch between an incoming stimulus and representations of previously presented stimuli (Näätänen 1992). Evidence from dipole source modeling (Scherg et al 1989) suggests that the difference wave used to isolate the MMN does not reflect a unitary phenomenon but can be divided into two parts: 1) a component that represents the activation of nonrefractory auditory neurons; and 2) a “true” mismatch process.

Whether the MMN is impaired in patients with schizophrenia as compared with age-matched controls remains equivocal. Catts et al (1995) found that patients with schizophrenia had reduced MMN for deviant tones that were either longer or shorter than the standard stimuli. The attenuation was greater for the MMN elicited by long deviant stimuli than by short deviant stimuli. Javitt et al (1995) found a reduction in MMN amplitude in medicated and unmedicated schizophrenics for relatively small changes in pitch (i.e., 1024 vs. 1000 Hz); however, O’Donnell et al (1994) failed to find a difference in MMN amplitude between schizophrenics and controls using large pitch-deviant stimuli (see also Kathmann et al 1995). It is difficult to understand why only small pitch changes yielded an MMN attenuation in patients with schizophrenia. One possibility is that large pitch changes trigger both nonrefractory auditory neurons and mismatch processes, whereas small pitch changes trigger primarily mismatch processing (Näätänen 1992), which is thought to be impaired in patients with schizophrenia Catts et al 1995, Javitt et al 1995. If so, differing duration of deviant stimuli should have produced a different pattern of results, i.e., a greater attenuation for MMN elicited by shorter than longer deviant tones. A more likely possibility is that the discrepancies between the studies result from procedural differences such as the discriminability between stimuli composing the sequence and the control and monitoring of participants’ attention. Numerous studies have shown that attention can enhance the amplitude of the MMN Alain and Woods 1997, Naatanen et al 1993, Trejo et al 1995, Woldorff et al 1991; however, previous studies of schizophrenic patients neither control for participants’ attention (Javitt et al 1995) nor report subject performance in the primary task Catts et al 1995, Kathmann et al 1995, O’Donnell et al 1994. Thus, it remains possible that the amplitude difference between the patients and the controls found in some of the previous studies resulted from different attentional strategies, e.g., control subjects may have paid more attention to the auditory stimuli than did the patients. Conversely, the lack of group difference observed in some of the studies may be due to the fact that patients were paying attention to the auditory stimuli instead of performing the primary task (e.g., reading).

In the present study, participants’ attention was controlled and monitored using a challenging visual discrimination task. While doing the visual task, participants were presented with either 1) a sequence of identical tones that included small and large pitch deviant stimuli or 2) a sequence of tones alternating regularly in pitch with deviant repetitions. The auditory sequences were presented either to the left or right ear to evaluate potential asymmetry (e.g., Bruder et al 1995). Small and large pitch deviant stimuli were used to examine the effect of discriminability on the MMN. Lastly, different auditory sequences were used to ensure the generalizability for patterns of different complexity. The alternating tone pattern is particularly well suited to evaluate mismatch processes, because this MMN does not receive any contribution from new afferent input, since it is elicited by the repetition of a tone. Thus, if the MMN decrement in schizophrenia results from a fundamental impairment in the mismatch process, we should observe impaired MMN generation for both pattern and pitch deviance.