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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.

SUBMITTER: Joutsa J

PROVIDER: S-EPMC9205767 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThe efficacy of clinical interventions for post-stroke spasticity (PSS) has been consistently unsatisfactory, probably because lesions causing PSS may occur at different locations in the brain, leaving the neuroanatomical substrates of spasticity unclear. Here, we investigated whether heterogeneous lesions causing PSS were localized to a common brain network and then identified the key nodes in this network.MethodsWe used 32 cases of PSS and the Human Connectome dataset (n = 1,000), using a lesion network mapping method to identify the brain regions that were associated with each lesion in patients with PSS. Functional connectivity maps of all lesions were overlaid to identify common connectivity. Furthermore, a split-half replication method was used to evaluate reproducibility. Then, the lesion network mapping results were compared with those of patients with post-stroke non-spastic motor dysfunction (n = 29) to assess the specificity. Next, both sensitive and specific regions associated with PSS were identified using conjunction analyses, and the correlation between these regions and PSS was further explored by correlation analysis.ResultsThe lesions in all patients with PSS were located in different cortical and subcortical locations. However, at least 93% of these lesions (29/32) had functional connectivity with the bilateral putamen and globus pallidus. These connections were highly repeatable and specific, as compared to those in non-spastic patients. In addition, the functional connectivity between lesions and bilateral putamen and globus pallidus in patients with PSS was positively correlated with the degree of spasticity.ConclusionWe identified that lesions causing PSS were localized to a common functional connectivity network defined by connectivity to the bilateral putamen and globus pallidus. This network may best cover the locations of lesions causing PSS. The putamen and globus pallidus may be potential key regions in PSS. Our findings complement previous neuroimaging studies on PSS, contributing to identifying patients with stroke at high risk for spasticity at an early stage, and may point to PSS-specific brain stimulation targets.

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Brain lesions disrupting addiction map to a common human brain circuit.

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