The neural correlates of illness awareness in addiction: A pilot exploratory analysis of preliminary data from the Cognitive Dysfunction in the Addictions Study

Shannen Kyte^1,2Jianmeng Song^3,4Yuliya S Nikolova^5,6,7Anthony C. Ruocco^5,6,7,8Sri Mahavir Agarwal^3,5,6Aron Amaev^3,4Danielle Bukovsky^3,4Edgardo Carmona-Torres^3,4Daniel Felsky^5,6,9Ariel Graff-Guerrero^3,4,5Shannon Lange^10,3,5,6Thomas PREVOT^11,5,6Lena Catherine Quilty^5,6Gary Remington^3,5,6Etienne Sibille^11,5,6Antonio P Strafella^12,3,5Fumihiko Ueno⁴Erica Vieira^5,6Daphne Voineskos^5,6Philip Gerretsen^3,4,5,6*

• ¹Institute of Medical Science, University of Toronto, Toronto, Canada
• ²Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
• ³University of Toronto Institute of Medical Science, Toronto, Canada
• ⁴Centre for Addiction and Mental Health Research Imaging Centre Multimodal Imaging Group, Toronto, Canada
• ⁵Centre for Addiction and Mental Health Campbell Family Mental Health Research Institute, Toronto, Canada
• ⁶University of Toronto Department of Psychiatry, Toronto, Canada
• ⁷University of Toronto Department of Psychological Clinical Science, Toronto, Canada
• ⁸University of Toronto Scarborough Department of Psychology, Toronto, Canada
• ⁹University of Toronto Dalla Lana School of Public Health, Toronto, Canada
• ¹⁰Centre for Addiction and Mental Health Institute of Mental Health Policy Research, Toronto, Canada
• ¹¹University of Toronto Temerty Faculty of Medicine Department of Pharmacology and Toxicology, Toronto, Canada
• ¹²University of Toronto University Health Network Temerty Faculty of Medicine Toronto Western Hospital & Krembil Brain Institute Neurology Division Edmond J. Safra Parkinson Disease Program, Toronto, Canada

Background: Impaired illness awareness or anosognosia is common in substance use disorders (SUDs), including alcohol use disorder (AUD), and is a significant barrier to treatment engagement. Neuroimaging studies of the neural correlates of impaired illness awareness in other conditions have observed functional differences in regions involved in self-referential processing, namely the frontoparietal and insular areas. This study aimed to extend this research to impaired illness awareness in SUDs. Methods: Twenty participants with AUD (n = 10) or other SUDs (n = 10) (age = 35.10 (± 10.59), 80% male) were recruited from the Cognitive Dysfunction in Addictions (CDiA) research program at the Centre for Addiction and Mental Health in Toronto, Canada. Participants completed an illness awareness task during a functional MRI scan consisting of brief questions/statements derived from the core domains of illness awareness. Illness awareness was assessed based on response accuracy to the illness-related stimuli. Participants were grouped into impaired (≤77% response accuracy, n=10) versus intact (≥77%, n=10) illness awareness. Regression and non-parametric between-group analyses were conducted to assess brain activity, as measured by blood oxygen level dependent (BOLD) response during the illness awareness task for the AUD and other SUD groups combined and separately. Regions of interest were the posterior parietal area (PPA), dorsolateral prefrontal cortex (dlPFC), and insula. Results: Individuals with impaired illness awareness had significantly greater activation than individuals with intact illness awareness in the right insula in the AUD and SUD combined group and in the left PPA (i.e., supramarginal gyrus) in the AUD subgroup. These results were no longer significant after including illness severity as a covariate and controlling for substance category in the combined group. Conclusion: The results of this pilot exploratory study cautiously suggest that similar to other conditions that feature impaired illness awareness, subjective addiction awareness may be related to heightened frontoparietal and insular brain activity. However, no findings were significant after correction for multiple testing, hence, further study in a larger sample is required to establish brain regions associated with subjective substance use awareness.