The Brain Salience Network at the Intersection of Pain and Substance use Disorders: Insights from Functional Neuroimaging Research.

Purpose of Review: The brain's salience network (SN), primarily comprising the anterior insula and anterior cingulate cortex, plays a key role in detecting salient stimuli and processing physical and socioemotional pain (e.g., social rejection). Mounting evidence underscores an altered SN in the etiology and maintenance of substance use disorders (SUDs). This paper aims to synthesize recent functional neuroimaging research emphasizing the SN's involvement in SUDs and physical/socioemotional pain and explore the therapeutic prospects of targeting the SN for SUD treatment. Recent Findings: The SN is repeatedly activated during the experience of both physical and socioemotional pain. Altered activation within the SN is associated with both SUDs and chronic pain conditions, characterized by aberrant activity and connectivity patterns as well as structural changes. Among individuals with SUDs, functional and structural alterations in the SN have been linked to abnormal salience attribution (e.g., heightened responsiveness to drug-related cues), impaired cognitive control (e.g., impulsivity), and compromised decision-making processes. The high prevalence of physical and socioemotional pain in the SUD population may further exacerbate SN alterations, thus contributing to hindered recovery progress and treatment failure. Interventions targeting the restoration of SN functioning, such as real-time functional MRI feedback, neuromodulation, and psychotherapeutic approaches, hold promise as innovative SUD treatments. Summary: The review highlights the significance of alterations in the structure and function of the SN as potential mechanisms underlying the co-occurrence of SUDs and physical/socioemotional pain. Future work that integrates neuroimaging with other research methodologies will provide novel insights into the mechanistic role of the SN in SUDs and inform the development of next-generation treatment modalities.