Deficits in attentional modulation of auditory N100 in first-episode schizophrenia

Abstract

Reductions of the auditory N100 are present in schizophrenia, even at the first episode (FESz). Because most studies examine auditory N100 on active target detection oddball tasks, it remains unclear if the abnormality in FESz results from sensory deficits or impaired enhancement of N100 by selective attention, or both. N100 was recorded from 21 FESz and 22 matched healthy controls (HC) on a single-tone task and a two-tone oddball task. Overall, N100 was smaller in FESz (p = .036). Attention enhanced N100 amplitude (p < .001), but this differed between groups, with FESz impaired in N100 modulation (group x attention, p = .012). The oddball task showed greater N100 enhancement than the single-tone task (p < .001) in both groups. Group differences in N100 enhancement in the oddball task were large (Cohen's d = 0.85). Exploratory correlations showed that better N100 enhancement on the oddball task in FESz was associated with better MATRICS Overall Composite scores (cognitive tasks highly sensitive to psychosis), lower PANNS Negative factor and SANS scores, and better interpersonal (social) and role functioning in the last year. N100 during ignore conditions showed no significant difference between groups, albeit smaller in FESz, with small to medium effect sizes. Although sensory deficits in N100 are likely present, they are compounded by a failure to enhance N100 with attention. The failure of N100 enhancement by attentional gain control in FESz suggests functional dysconnection between cognitive control areas and the sensory cortex. N100 amplitude on active attention tasks may be a useful outcome biomarker for targeted enhancement of the cognitive control system.

Keywords: N100; attention; enhancement; first episode psychosis; gain; schizophrenia.

Figure 1.. N100 Averages.

A. Attend and ignore single-tone task (AEP) waveforms for HC (left panel) and FESz (right panel). B. Attend and ignore oddball task standard tone waveforms for HC (left panel) and FESz (right panel). Note the generally larger increase in N100 with attention in both groups, albeit larger in HC. C. Attend and ignore oddball task target/deviant tone ERP waveforms for HC (left panel) and FESz (right panel). The presence of P300 in attend but not ignore conditions indicates the controlled deployment of selective attention. HC = Healthy comparison participants. FESz = First-episode schizophrenia participants. Shaded area indicates peak N100 ± 5msec.

Figure 2.. N100 peak ±10 msec amplitudes and N100 enhancement.

A. Single-tone (AEP) task N100 distributions at Fz for ignore and attend conditions in each group. B. N100 enhancement by attention on the AEP task for each group. C. Two-tone (oddball) task N100 distributions at Fz for ignore and attend conditions in each group. D. N100 enhancement by attention on the oddball task for each group. Note: Bars in the scattergrams represent the group mean. Statistics are for uncorrected t-tests.