Common Lesion-Derived Circuitry Across Addiction Remission and Apathy

Background: Lesions associated with remission from nicotine and alcohol addiction map to a common brain circuit with positive connectivity to the dorsal cingulate and insula, and negative connectivity to the medial prefrontal cortex (mPFC).1 Dopamine-related states such as apathy have also been associated with lesions to the dorsal cingulate and mPFC.2-4 Here we compare the addiction remission circuit to lesions associated with apathy.

Methods: We used a normative human connectome database (n=1000) to map the functional connectivity of 164 penetrating head trauma lesions. Spearman’s partial correlation was computed at each voxel to compare lesion connectivity and apathy severity on the Neuropsychiatric Inventory Questionnaire, controlling for Beck Depression Inventory, Mini-Mental Status Exam, and lesion size. The resulting apathy circuit was spatially correlated with the addiction remission map. Significance was assessed using permutation testing in which each patient’s imaging was randomly shuffled against a different patient’s apathy score.

Results: Apathy was greatest after lesions connected to a circuit with positive connectivity to the mPFC and fornix near the septal nuclei, and negative connectivity to the left intraparietal sulcus. The apathy circuit was negatively correlated with the addiction remission network (r=-0.65, p<0.05). This result remained unchanged when controlling for MacAndrews Alcoholism Risk score in the apathy dataset (r=-0.67, p<0.05). Conclusions: The connectivity profile of lesions associated with apathy was inversely correlated with the addiction remission circuit. Both circuits contained peaks in the mPFC, a region that projects to dopamine-producing neurons in the basal ganglia.5 These results suggest common circuitry across two dopamine-related conditions. References Joutsa, J., Moussawi, K., Siddiqi, S. H., Abdolahi, A., Drew, W., Cohen, A. L., … & Fox, M. D. (2022). Brain lesions disrupting addiction map to a common human brain circuit. Nature medicine, 28(6), 1249-1255. Horne, K. S., Gibson, E. C., Byrne, J., Bender, J. R., & Robinson, G. A. (2022). Post-stroke apathy: A case series investigation of neuropsychological and lesion characteristics. Neuropsychologia, 171, 108244. Knutson, K. M., Dal Monte, O., Raymont, V., Wassermann, E. M., Krueger, F., & Grafman, J. (2014). Neural correlates of apathy revealed by lesion mapping in participants with traumatic brain injuries. Human brain mapping, 35(3), 943-953. Kos, C., van Tol, M. J., Marsman, J. B. C., Knegtering, H., & Aleman, A. (2016). Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders. Neuroscience & Biobehavioral Reviews, 69, 381-401. Hui, M., & Beier, K. T. (2022). Defining the interconnectivity of the medial prefrontal cortex and ventral midbrain. Frontiers in Molecular Neuroscience, 15, 971349.