Working memory-related activity in catecholaminergic nuclei in schizophrenia

Abstract Schizophrenia is a complex psychiatric condition in which cortical, subcortical and neuromodulatory alterations have been implicated in its symptom expression. Long standing views of schizophrenia symptoms have posed that alterations in catecholaminergic systems, which explain psychotic symptoms, may be also associated with the cognitive impairments commonly observed in this condition. However, evidence on the involvement of catecholaminergic regions on cognitive functions in schizophrenia remains scarce. Working memory is one cognitive domain where schizophrenia patients present more impairments at higher levels of cognitive load. Here we explored the activation of catecholaminergic regions during a working memory task in schizophrenia. We reanalyzed an openly available functional magnetic resonance imaging dataset where schizophrenia patients and healthy controls were scanned while performing the N-back task. We compared activation of two dopaminergic areas, ventral tegmental area and substantia nigra, and of a noradrenergic nucleus, locus coeruleus, to the presentation of targets, and compared three different levels of cognitive load (0-, 1– and 2-back). We found that across nuclei, higher load was related to lower activation. Furthermore, schizophrenia patients showed reduced activation at the highest load level when compared to healthy controls. These findings point to catecholaminergic systems as mediators of the deficits in effort processing in schizophrenia. Our study lends further support for the importance of including catecholaminergic systems in the mechanisms of cognitive deficits in schizophrenia.