Frontiers in neurology · 2026
The neural correlates of illness awareness in addiction: a pilot exploratory analysis of preliminary data from the cognitive dysfunction in the addictions (CDiA) research program.
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Kyte Shannen, Song Jianmeng, Nikolova Yuliya S, Ruocco Anthony C, Agarwal Sri Mahavir, Amaev Aron, Bukovsky Danielle, Carmona-Torres Edgardo, Felsky Daniel, Graff-Guerrero Ariel, Lange Shannon, Prevot Thomas D, Quilty Lena C, Remington Gary, Sibille Etienne, Strafella Antonio P, Ueno Fumihiko, Vieira Erica, Voineskos Daphne, Gerretsen Philip
Аннотация
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. In the SUD subgroup, impaired illness awareness was associated with higher activation in the right dlPFC (i.e., medial superior frontal gyrus); however, this finding did not survive family-wise error correction.
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 increased frontoparietal and insular brain activity during an fMRI illness awareness task. 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.
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. In the SUD subgroup, impaired illness awareness was associated with higher activation in the right dlPFC (i.e., medial superior frontal gyrus); however, this finding did not survive family-wise error correction.
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 increased frontoparietal and insular brain activity during an fMRI illness awareness task. 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.