Neuronal effects of nicotine during auditory selective attention in schizophrenia

Although nicotine has been shown to improve attention deficits in schizophrenia, the neurobiological mechanisms underlying this effect are poorly understood. We hypothesized that nicotine would modulate attention-associated neuronal response in schizophrenia patients in the ventral parietal cortex (VPC), hippocampus, and anterior cingulate based on previous findings in control subjects. To test this hypothesis, the present study examined response in these regions in a cohort of nonsmoking patients and healthy control subjects using an auditory selective attention task with environmental noise distractors during placebo and nicotine administration. In agreement with our hypothesis, significant diagnosis (Control vs. Patient) X drug (Placebo vs. Nicotine) interactions were observed in the VPC and hippocampus. The interaction was driven by task-associated hyperactivity in patients (relative to healthy controls) during placebo administration, and decreased hyperactivity in patients after nicotine administration (relative to placebo). No significant interaction was observed in the anterior cingulate. Task-associated hyperactivity of the VPC predicted poor task performance in patients during placebo. Poor task performance also predicted symptoms in patients as measured by the Brief Psychiatric Rating Scale. These results are the first to suggest that nicotine may modulate brain activity in a selective attention-dependent manner in schizophrenia.