Auditory orienting and inhibition of return in schizophrenia: a functional magnetic resonance imaging study

Abstract

Patients with schizophrenia (SP) exhibit deficits in both attentional reorienting and inhibition of return (IOR) during visual tasks. However, it is currently unknown whether these deficits are supramodal in nature and how these deficits relate to other domains of cognitive dysfunction. In addition, the neuronal correlates of this pathological orienting response have not been investigated in either the visual or auditory modality. Therefore, 30 SP and 30 healthy controls (HC) were evaluated with an extensive clinical protocol and functional magnetic resonance imaging (fMRI) during an auditory cuing paradigm. SP exhibited both increased costs and delayed IOR during auditory orienting, suggesting a prolonged interval for attentional disengagement from cued locations. Moreover, a delay in the development of IOR was associated with cognitive deficits on formal neuropsychological testing in the domains of attention/inhibition and working memory. Event-related fMRI showed the characteristic activation of a frontoparietal network (invalid trials>valid trials), but there were no differences in functional activation between patients and HC during either attentional reorienting or IOR. Current results suggest that orienting deficits are supramodal in nature in SP, and are related to higher-order cognitive deficits that directly interfere with day-to-day functioning.

Figure 1

Mean reaction time (RT) in milliseconds (ms) at each stimulus onset asynchrony (SOA) for patients (SP; Panel A) and controls (HC; Panel B). Grey triangles were used to represent valid trials and black squares for invalid trials. Panel C exhibits validity effects (invalid RT – valid RT) at each SOA for patients (SP; black) and controls (HC; white). Error bars correspond to two times the standard error of the mean for all data.

Figure 2

Invalid trials were associated with widespread bilateral activity in several regions including (Panel A) pre-supplementary/supplementary motor area (Pre-SMA/SMA), frontal eye fields (FEF), dorsolateral prefrontal cortex (DLPFC), and posterior parietal lobe (PPL). The left ventrolateral prefrontal cortex (VLPFC) was also active during invalidly cued trials. Slice locations (X and Z) are presented according to the Talairach atlas, and activations were color-coded (red versus yellow) according to p-value magnitude. Percent signal change (PSC) data is presented in Panel B for valid (VD; red bars) and invalid (IN; blue bars) trials for selected left (L), right (R) and bilateral (B) regions, with error bars equivalent to two times the standard error of the mean.

Figure 3

Panel A presents regions exhibiting a main effect of stimulus onset asynchrony (SOA), with slice locations (X and Z) presented according to the Talairach atlas. Panels B-D present the percent signal change (PSC) data from selected regions at the 200 (red), 400 (blue), 600 (orange) and 800 (green) ms SOA intervals. In Panel B, the main effect of SOA was associated with increasing activation as a function of SOA in the bilateral primary and secondary auditory cortex (AC). Panel C shows how activation within the bilateral precuneus (B Prc) and pre-supplementary motor area (Pre-SMA) decreased as a function of SOA. Finally, activation within the bilateral middle frontal gyrus (MFG), bilateral occipital gyri (OG; percent signal change data not presented) and left ventrolateral prefrontal cortex (L VLPFC) decreased as a function of SOA, with deactivation present at longer SOAs (Panel D).