Brain lesions disrupting addiction map to a common human brain circuit

Abstract

Drug addiction is a public health crisis for which new treatments are urgently needed. In rare cases, regional brain damage can lead to addiction remission. These cases may be used to identify therapeutic targets for neuromodulation. We analyzed two cohorts of patients addicted to smoking at the time of focal brain damage (cohort 1 n = 67; cohort 2 n = 62). Lesion locations were mapped to a brain atlas and the brain network functionally connected to each lesion location was computed using human connectome data (n = 1,000). Associations with addiction remission were identified. Generalizability was assessed using an independent cohort of patients with focal brain damage and alcohol addiction risk scores (n = 186). Specificity was assessed through comparison to 37 other neuropsychological variables. Lesions disrupting smoking addiction occurred in many different brain locations but were characterized by a specific pattern of brain connectivity. This pattern involved positive connectivity to the dorsal cingulate, lateral prefrontal cortex, and insula and negative connectivity to the medial prefrontal and temporal cortex. This circuit was reproducible across independent lesion cohorts, associated with reduced alcohol addiction risk, and specific to addiction metrics. Hubs that best matched the connectivity profile for addiction remission were the paracingulate gyrus, left frontal operculum, and medial fronto-polar cortex. We conclude that brain lesions disrupting addiction map to a specific human brain circuit and that hubs in this circuit provide testable targets for therapeutic neuromodulation.

Pathological fear, anxiety and negative affect exhibit distinct neurostructural signatures: evidence from psychiatric neuroimaging meta-analysis

“…Recent preclinical studies have demonstrated the potential of real-time fMRI-informed neurofeedback to modulate brain systems and circuits traditionally implicated in internalizing disorders [ 135 , 174 , 175 ] and suggest that the neurofeedback training success is associated with variations in regional GMV [ 176 ]. The efficacy of these interventions can benefit from the identification of robust and disorder-specific therapeutic targets from our comparative meta-analyses or other approaches (e.g., lesion network mapping [ 177 ]).…”

Functional neuroimaging in psychiatry and the case for failing better

“…Outcome variability in focal neuromodulation studies might reflect a host of factors, including suboptimal stimulation targets, and functional neuroimaging (e.g., resting-state fMRI) may yet play a role in assessing target selection and engagement in individual patients (Cash et al, 2021;Cole et al, 2020Cole et al, , 2022Fitzgerald, 2021;Fox et al, 2012;Nord et al, 2019;Price et al, 2021;Siddiqi et al, 2021a;Weigand et al, 2018;Weissman and Daskalakis, 2022). Furthermore, neuroimaging-based techniques such as lesion network mapping show promise in identifying new anatomical targets that are causally implicated in therapeutic change (Joutsa et al, 2022;Siddiqi et al, 2020Siddiqi et al, , 2021bSiddiqi et al, , 2022. Nevertheless, it remains the case that mappings between neuroanatomical loci and psychiatric diagnoses or symptoms have remained elusive.…”

Lesion network mapping for symptom localization: recent developments and future directions

“…These findings may have important clinical implications given that the identification of effective treatment targets for addiction disorders has been exceptionally challenging, resulting in numerous neuromodulation trials with no consensus regarding the optimal targets [33]. Independent of the LNM study by Joutsa et al [30 ▪ ], two recently published large trials (one to facilitate smoking cessation, one to reduce craving in alcoholism) reported positive results with specific coil designs [34,35]. Although these studies did not intend to target the regions identified using LNM, the peaks of these coil electric fields overlapped remarkably well with the cortical network peak of the addiction remission network, demonstrating the potential therapeutic relevance of mapping brain circuits from beneficial brain lesions.…”

“…In addition, a recent study applied this approach to lesions improving addiction, and localized a brain circuit thought to mediate smoking addiction remission [30 ▪ ]. Specifically, lesions resulting in smoking addiction remission showed positive connectivity to the insula and paracingulate cortex, and negative connectivity to the medial prefrontal cortex.…”