David D. Stephenson, PhD; Ansam A. El Shaikh, PhD; Nicholas A. Shaff, BS; Juan R. Bustillo, MD; Andrew B. Dodd, MS; Christopher J. Wertz, BS; Sephira G. Ryman, PhD; Faith M. Hanlon, PhD; Jeremy P. Hogeveen, PhD; Josef M. Ling, BA; Ronald A. Yeo, PhD; Shannon F. Stromberg, MD; Denise S. Lin, MD; Swala Abrams, MD; Andrew R. Mayer, PhD
Background: Functional underpinnings of cognitive control deficits in unbiased samples (i.e., all comers) of patients with psychotic spectrum disorders (PSD) remain actively debated. While many studies suggest hypofrontality in the lateral prefrontal cortex (PFC) and greater deficits during proactive relative to reactive control, few have examined the full hemodynamic response.
Methods: Patients with PSD (n = 154) and healthy controls (n = 65) performed the AX continuous performance task (AX-CPT) during rapid (460 ms) functional neuroimaging and underwent full clinical characterization.
Results: Behavioural results indicated generalized cognitive deficits (slower and less accurate) across proactive and reactive control conditions in patients with PSD relative to healthy controls. We observed a delayed/prolonged neural response in the left dorsolateral PFC, the sensorimotor cortex and the superior parietal lobe during proactive control for patients with PSD. These proactive hemodynamic abnormalities were better explained by negative rather than by positive symptoms or by traditional diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR), with subsequent simulations unequivocally demonstrating how these abnormalities could be erroneously interpreted as hypoactivation. Conversely, true hypoactivity, unassociated with clinical symptoms or DSM-IV-TR diagnoses, was observed within the ventrolateral PFC during reactive control.
Limitations: In spite of guidance for AX-CPT use in neuroimaging studies, one-third of patients with PSD could not perform the task above chance and were more clinically impaired.
Conclusion: Current findings question the utility of the AX-CPT for neuroimaging-based appraisal of cognitive control across the full spectrum of patients with PSD. Previously reported lateral PFC “hypoactivity” during proactive control may be more indicative of a delayed/prolonged neural response, important for rehabilitative purposes. Negative symptoms may better explain certain behavioural and hemodynamic abnormalities in patients with PSD relative to DSM-IV-TR diagnoses.
Submitted Feb. 27, 2020; Revised Apr. 13, 2020; Accepted May 23, 2020; Published online Aug. 31, 2020
Acknowledgments: This work was supported by the National Institutes of Health (grant number 1RO1MH101512-03 to ARM). The authors thank Diana South and Catherine Smith for their assistance with data collection.
Affiliations: From the The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, USA (Stephenson, Shaikh, Shaff, Dodd, Wertz, Ryman, Hanlon, Ling, Mayer); the Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, NM, USA (Bustillo, Stromberg, Lin, Abrams, Mayer); the Department of Psychology, University of New Mexico, Albuquerque, NM, USA (Hogeveen, Yeo, Mayer); and the Department of Neurology, University of New Mexico School of Medicine, Albuquerque, NM, USA (Mayer).
Competing interests: None declared.
Contributors: D. Stephenson, R. Yeo and A. Mayer designed the study. N. Shaff, J. Bustillo, A. Dodd, C. Wertz, F. Hanlon, S. Stromberg, D. Lin, S. Abrams and A. Mayer acquired the data, which D. Stephenson, A. El Shaikh, N. Shaff, A. Dodd, S. Ryman, F. Hanlon, J. Hogeveen, J. Ling, S. Abrams and A. Mayer analyzed. D. Stephenson, A. El Shaikh, N. Shaff, A. Dodd, C. Wertz, S. Stromberg and A. Mayer 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: A. Mayer, Mind Research Network, Pete and Nancy Domenici Hall, 1101 Yale Blvd NE, Albuquerque, NM 87106 USA; firstname.lastname@example.org