Yu Fukuda, MSc; Teresa Katthagen, PhD; Lorenz Deserno, MD; Leila Shayegan, BA; Jakob Kaminski, MD; Andreas Heinz, PhD, MD; Florian Schlagenhauf, MD
Background: Working-memory impairment is a core cognitive dysfunction in people with schizophrenia and people at mental high risk. Recent imaging studies on working memory have suggested that abnormalities in prefrontal activation and in connectivity between the frontal and parietal regions could be neural underpinnings of the different stages of psychosis. However, it remains to be explored whether comparable alterations are present in people with subclinical levels of psychosis, as experienced by a small proportion of the general population who neither seek help nor show constraints in daily functioning.
Methods: We compared 24 people with subclinical high delusional ideation and 24 people with low delusional ideation. Both groups performed an n-back working-memory task during functional magnetic resonance imaging. We characterized frontoparietal effective connectivity using dynamic causal modelling.
Results: Compared to people who had low delusional ideation, people with high delusional ideation showed a significant increase in dorsolateral prefrontal activation during the working-memory task, as well as reduced working-memory-dependent parietofrontal effective connectivity in the left hemisphere. Group differences were not evident at the behavioural level.
Limitations: The current experimental design did not distinguish among the working-memory subprocesses; it remains unexplored whether differences in connectivity exist at that level.
Conclusion: These findings suggest that alterations in the working-memory network are also present in a nonclinical population with psychotic experiences who do not display cognitive deficits. They also suggest that alterations in working-memory-dependent connectivity show a putative continuity along the spectrum of psychotic symptoms.
Submitted Mar. 20, 2018; Revised Jul. 20, 2018; Accepted Aug. 22, 2018; Published online Jan. 15, 2019
Acknowledgements: This study was supported by grants from the German Research Foundation (DFG SCHL1969/1-1&2, DFG SCHL 1969/3-1, DFG SCHL 1969/4-1) and the Max Planck Society (to F. Schlagenhauf); a travel grant from GlaxoSmithKline Stiftung (to Y. Fukuda); the Elsa Neumann Scholarship of the city of Berlin (to T. Katthagen); a Fulbright Grant of the German–American Fulbright Commission (to L. Shayegan); a Berlin School of Mind & Brain postdoc scholarship (to T. Katthagen); a Junior Clinician Scientist (to J. Kaminski); and German Federal Ministry of Education and Research grants (01GQ0411, 01QG87164, NGFN Plus 01 GS 08152, 01 GS 08159 to A. Heinz). The authors thank further members of the work group for their assistance during data acquisition.
Affiliations: From the Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany (Fukuda, Katthagen, Kaminski, Heinz, Schlagenhauf); the Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany (Deserno); Department of Neurology, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Deserno, Kaminski, Schlagenhauf); the Columbia University College of Physicians and Surgeons, New York, NY (Shayegan); and the Berlin Institute of Health, Berlin, Germany (Kaminski).
Competing interests: None declared.
Contributors: L. Deserno, A. Heinz and F. Schlagenhauf designed the study. Y. Fukuda, T. Katthagen and J. Kaminski acquired and analyzed the data, which L. Deserno, L. Shayegan and F. Schlagenhauf also analyzed. Y. Fukuda, T. Katthagen and F. Schlagenhauf wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.
Correspondence to: Yu Fukuda, Department of Psychiatry and Psychotherapy, Charité–Universitätsmedizin Berlin, Campus Mitte Charitéplatz 1, 10117 Berlin, Germany; firstname.lastname@example.org