Translational Research on Sustained Attention and Attentional Control in Rats, Healthy Humans and Patients with Schizophrenia.

Abstract

Attentional deficits are often studied in schizophrenia, yet treatments to alleviate these impairments remain undeveloped. In part, this gap between basic and clinical research stems from a lack of tasks validated for translational research. The current work develops the distractor condition sustained attention task (dSAT), an attentional control paradigm traditionally used in rats to investigate the cholinergic system’s role in attention, for cross-species, translational research by adapting it for use in humans. In the basic sustained attention task (SAT), subjects report the presence or absence of a brief, centrally-presented signal of varying duration. In the distractor condition (dSAT), a visual distractor evokes top-down control mechanisms in order to stabilize performance. The current work demonstrates that rats and healthy, young human adults have qualitatively similar patterns of performance on the SAT and dSAT, including decreased attentional performance during distraction. Neuroimaging in young human adults shows that this decreased attentional performance is correlated with increased activation of right middle frontal gyrus (MFG). The sensitivity of right MFG to the attentional effort demands in the dSAT is of interest because this region is implicated as a site of disruption in patients with schizophrenia (Minzenberg et al., 2009). To investigate the dSAT’s sensitivity to attentional deficits in schizophrenia, stable, medicated schizophrenic outpatients and healthy controls were tested on the dSAT. Healthy children were also tested to compare the patients to a group with similar overall accuracy levels. While patients are only minimally impaired on the task in the absence of distraction, their attentional performance levels decline dramatically during distraction, exceeding the declines seen in healthy adult controls or children. Children also show time-on-task declines in SAT performance, suggesting that impairments on the SAT and dSAT may be dissociable in different populations. The ability to implement the dSAT in both rat psychopharmacological and neurochemical experiments and human neuroimaging research, as well as the dSAT’s sensitivity to the cognitive deficits in schizophrenia, makes the dSAT a useful instrument for translational research on attention systems in animal models of cognitive disorders, healthy human subjects, and patients with neuropsychiatric disorders.