Intracranial subsecond dopamine measurements during a “sure bet or gamble” decision-making task in patients with alcohol use disorder suggest diminished dopaminergic signals about relief

Abstract

OBJECTIVE To the authors’ knowledge, no data have been reported on dopamine fluctuations on subsecond timescales in humans with alcohol use disorder (AUD). In this study, dopamine release was monitored in 2 patients with and 2 without a history of AUD during a “sure bet or gamble” (SBORG) decision-making task to begin to characterize how subsecond dopamine responses to counterfactual information, related to psychological notions of regret and relief, in AUD may be altered. METHODS Measurements of extracellular dopamine levels were made once every 100 msec using human voltammetric methods. Measurements were made in the caudate during deep brain stimulation electrode implantation surgeries (for treatment of movement disorders) in patients who did (AUD, n = 2) or did not (non-AUD, n = 2) have a history of AUD. Participants performed an SBORG decision-making task in which they made choices between sure bets and 50%-chance monetary gamble outcomes. RESULTS Fast changes were found in dopamine levels that appear to be modulated by “what could have been” and by patients’ AUD status. Positive counterfactual prediction errors (related to relief) differentiated patients with versus without a history of AUD. CONCLUSIONS Dopaminergic encoding of counterfactual information appears to differ between patients with and without AUD. The current study has a major limitation of a limited sample size, but these data provide a rare insight into dopaminergic physiology during real-time decision-making in humans with an addiction disorder. The authors hope future work will expand the sample size and determine the generalizability of the current results.

Sub-second Dopamine Signals during Risky Decision-Making in Patients with Impulse Control Disorder

“…Our group recently demonstrated that sub-second dopamine fluctuations in response to calculated relief values effectively separated patients with and without Alcohol Use Disorder (AUD). 19 Here we expand this approach to propose sub-second dopamine fluctuations from the dorsal striatum as potential future investigative anatomic structures for preclinical work on the origins of ICD. Our sample size was modest (n = 3 patients with ICD, n = patients without ICD), but our results align with previous human neuroimaging studies demonstrating dorsal striatal activation during risky decision-making in patients with ICD.…”

“…10–12 The insights gained by presenting sub-second dopamine fluctuations measured in the human operating room offer potential mechanisms underlying this debilitating behavioral addiction disorder for future neuroimaging and other pre-clinical work. 19…”

“…Recently, technology that allows safe measurements of dopamine release with sub-second temporal resolution in humans revealed changes in dopamine levels within hundreds of milliseconds of actions and events around risky decisions and their outcomes. [14][15][16][17][18] This approach uncovered novel characterization in behavioral and dopaminergic patterns in individuals with alcohol use disorder (AUD), 19 which is both a comorbidity and clinical predictor of ICD. 3,4,[20][21][22] In fact, a family history of alcohol disorders is a leading clinical predictor of ICD risk supported by several studies.…”

“…3,4,[20][21][22] In fact, a family history of alcohol disorders is a leading clinical predictor of ICD risk supported by several studies. 3,4,[19][20][21] One study of 3,090 PD patients found a statistically significant increase in prevalence in family history of alcohol disorders in first-degree relatives in ICD versus non-ICD patients. 3 A coinciding family or personal history of disordered alcohol or substance use has also been reported in around 28-30% of ICD patients.…”

“…Dopaminergic fluctuations serve as a bridge between behavioral addictions in ICD and the substance-based AUD; investigating underlying dopaminergic fluctuations in humans with and without ICD may allow us to define dopaminergic signatures underlying behavioral patterns for future investigation in humans and other models of addiction. Here, we build on this recent work in AUD 19 and apply a human voltammetry approach to investigate behavioral and dopaminergic fluctuation patterns in ICD.…”