Cortico-striatal engagement during cue-reactivity, reappraisal, and savoring of drug and non-drug stimuli predicts craving in heroin addiction
Authors: Huang Yuefeng , Ceceli Ahmet O. , Kronberg Greg , King Sarah , Malaker Pias , Alia-Klein Nelly , Garland Eric , Goldstein Rita Z. 
Published: May 2022

AbstractImportanceHeroin addiction is rampant and persistent, with devastating consequences to the public health, necessitating further study into the neurobiological mechanisms of drug cue-reactivity and craving-reducing interventions (e.g., reappraisal and savoring).ObjectiveTo document cortico-striatal reactivity during passive viewing, reappraisal, and savoring, as predictors of heroin craving in individuals with heroin use disorder (iHUD) vs. controls.DesignA cross-sectional study (11/2020-09/2021), with a novel fMRI task in iHUD vs. controls.SettingiHUD and controls were recruited from treatment facilities and surrounding neighborhoods, respectively.ParticipantsiHUD (N=32) [40.3±8.8 years; 7 (21.9%) women] and age-/sex-matched controls (N=21) [40.6±10.8 years; 8 (38%) women].Main Outcomes and MeasuresBetween-group blood-oxygen-level-dependent signal differences during cue-reactivity/reappraisal/savoring and their direct contrast (reappraisal vs. savoring), and correlations with drug craving in iHUD.ResultsDrug cue-reactivity (look drug>neutral) revealed higher nucleus accumbens and ventromedial prefrontal cortical activity in iHUD vs. controls (Z>3.1, p<.05), the latter positively correlated with post-task drug cravings (r2=.47, p<.001). In contrast, controls showed higher dorsolateral prefrontal cortex (dlPFC) and inferior frontal gyrus (IFG) reactivity to food cues (>drug; Z>3.1, p<.05; with the opposite pattern for the iHUD). Both drug-reappraisal and food-savoring (vs. respective passive viewing) showed increased activity in the IFG and supplementary motor area in all participants; the higher the dlPFC/IFG drug reappraisal in iHUD, the lower the post-MRI drug cue-induced craving (Z>3.1, p<.05). A direct comparison (drug-reappraisal vs. food-savoring) revealed higher drug-reappraisal in the ventral caudate and PFC regions in the iHUD (Z>3.1, p<.05), as predicted in the striatum by pre-task drug cravings (Z>2.57, p<.05); in controls, these areas showed instead higher food-savoring (Z>3.1, p<.05).Conclusions and RelevanceWe demonstrate upregulated cortico-striatal activity during drug-cue exposure (while passively looking or reappraising) and impaired reactivity during processing (looking or savoring) of non-drug rewards in heroin addiction. These results bolster the impaired response inhibition and salience attribution model of drug addiction, previously supported mostly by results in stimulant addiction. Normalizing cortico-striatal function by reducing drug cue-reactivity (e.g., reappraising drug cues) and enhancing natural reward valuation (e.g., savoring food stimuli) may inform therapeutic mechanisms for reducing drug craving/seeking in heroin addiction.Key PointsQuestionWhat are the cortico-striatal brain regions driving reactivity to and reappraisal of drug vs. savoring food cues in individuals with heroin use disorder (iHUD); do these activations contribute to self-reported drug cravings?FindingsIn this cross-sectional study, and compared to matched healthy control subjects, iHUD exhibited cortico-striatal reward and self-control regional hyperactivations to drug cues during both passive viewing of pictures and their reappraisal as compared to savoring of alternative reward (images of food); and these activations correlated with drug cravings.MeaningWe identified drug-cue biased processing in cortico-striatal regions in iHUD, providing potential therapeutic biomarkers for neuromodulation and cognitive training in reducing hyper-responsiveness to drug cues and enhancing responses to alternative natural rewards.