Working memory in schizophrenia: The role of the locus coeruleus and its relation to functional brain networks

Evidence suggests functional brain networks, especially the executive control network (ECN) and default mode network (DMN), to be abnormal in schizophrenia. Dysfunctions within the locus coeruleus (LC)-noradrenaline (NE) system, which is supposed to be pivotal to modulate neuronal network activation during executive control (e.g., working memory function), are also considered to play a vital role in the occurrence of positive (e.g., hallucinatory) or negative (e.g., inattentive) symptoms in these patients. In the present study, we sought to shed further light on the role of the LC-NE system in patients with schizophrenia. More specifically, we wanted to improve our understanding of the relationship and possible disturbances of the ECN and DMN during a working memory task in patients. A total of 58 healthy control subjects and 40 medicated patients with schizophrenia were investigated using a working memory 3-back task during functional magnetic resonance imaging. Main findings of our present study were differential dynamics of ECN and DMN blood oxygenation level-dependent (BOLD) activations with increasing task demands in both patients and controls. Moreover, we found increased BOLD activation in the LC in patients compared to controls in the interaction contrast between groups and conditions. LC BOLD activation significantly correlated with both, the main hub of the ECN, that is, the dorsolateral prefrontal cortex, and of the DMN, that is, the posterior cingulate cortex. Thus, the LC-NE system seems to be crucial in modulating neuronal network activity in a 3-back working memory task and might significantly contribute to cognitive impairments in schizophrenia.