Proactive response inhibition abnormalities in the sensorimotor cortex of patients with schizophrenia

Proactive response inhibition abnormalities in the sensorimotor cortex of patients with schizophrenia

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J Psychiatry Neurosci 2016;41(5):312-21

Andrew R. Mayer, PhD; Faith M. Hanlon, PhD; Andrew B. Dodd, MS; Ronald A. Yeo, PhD; Kathleen Y. Haaland, PhD; Josef M. Ling, BA; Sephira G. Ryman, MS

Abstract

Background: Previous studies of response inhibition in patients with schizophrenia have focused on reactive inhibition tasks (e.g., stop-signal, go/no-go), primarily observing lateral prefrontal cortex abnormalities. However, recent studies suggest that purposeful and sustained (i.e., proactive) inhibition may also be affected in these patients.

Methods: Patients with chronic schizophrenia and healthy controls underwent fMRI while inhibiting motor responses during multisensory (audiovisual) stimulation. Resting state data were also collected.

Results:
We included 37 patients with schizophrenia and 37 healthy controls in our study. Both controls and patients with schizophrenia successfully inhibited the majority of overt motor responses. Functional results indicated basic inhibitory failure in the lateral premotor and sensorimotor cortex, with opposing patterns of positive (schizophrenia) versus negative (control) activation. Abnormal activity was associated with independently assessed signs of psychomotor retardation. Patients with schizophrenia also exhibited unique activation of the pre–supplementary motor area (pre-SMA)/SMA and precuneus relative to baseline as well as a failure to deactivate anterior nodes of the default mode network. Independent resting-state connectivity analysis indicated reduced connectivity between anterior (task results) and posterior regions of the sensorimotor cortex for patients as well as abnormal connectivity between other regions (cerebellum, thalamus, posterior cingulate gyrus and visual cortex).

Limitations: Aside from rates of false-positive responses, true proactive response inhibition tasks do not provide behavioural metrics that can be independently used to quantify task performance.

Conclusion: Our results suggest that basic cortico-cortico and intracortical connections between the sensorimotor cortex and adjoining regions are impaired in patients with schizophrenia and that these impaired connections contribute to inhibitory failures (i.e., a positive rather than negative hemodynamic response).


Submitted Mar. 25, 2015; Revised July 20, 2015; Revised Aug. 14, 2015; Accepted Sept. 9, 2015; Early-released Feb. 17, 2016

Acknowledgements: The authors thank Diana South and Catherine Smith for their assistance with data collection. This work was supported by the National Institutes of Health (grant numbers NIGMS P20GM103472 and 1R01MH101512-01A1).

Affiliations: From the Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Pete & Nancy Domenici Hall, Albuquerque, NM (Mayer, Hanlon, Dodd, Ling, Ryman); the Neurology Department, University of New Mexico School of Medicine, Albuquerque, NM (Mayer, Haaland); the Psychology Department, University of New Mexico, Albuquerque, NM (Mayer, Yeo, Ryman); the Psychiatry Department, University of New Mexico School of Medicine, Albuquerque, NM (Haaland).

Competing interests: None declared.

Contributors: A. Mayer designed the study and acquired the data, which all authors analyzed. A. Mayer, F. Hanlon, A. Dodd, R. Yeo, K. Haaland and S. Ryman wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.150097

Correspondence to: A. Mayer, The Mind Research Network, Pete & Nancy Domenici Hall, 1101 Yale Blvd. NE, Albuquerque NM 87106; amayer@mrn.org