Dataset Information

Altered prefrontal signaling during inhibitory control in a salient drug context in cocaine use disorder.

ABSTRACT:

Introduction

Drug addiction is characterized by impaired response inhibition and salience attribution (iRISA), where the salience of drug cues is postulated to overpower that of other reinforcers with a concomitant decrease in self-control. However, the neural underpinnings of the interaction between the salience of drug cues and inhibitory control in drug addiction remain unclear.

Methods

We developed a novel stop-signal functional magnetic resonance imaging task where the stop-signal reaction time (SSRT-a classical inhibitory control measure) was tested under different salience conditions (modulated by drug, food, threat, or neutral words) in individuals with cocaine use disorder (CUD; n = 26) versus demographically matched healthy control participants (n = 26).

Results

Despite similarities in drug cue-related SSRT and valence and arousal word ratings between groups, dorsolateral prefrontal cortex (dlPFC) activity was diminished during the successful inhibition of drug versus food cues in CUD and was correlated with lower frequency of recent use, lower craving, and longer abstinence (Z > 3.1, P < 0.05 corrected).

Discussion

Results suggest altered involvement of cognitive control regions (e.g. dlPFC) during inhibitory control under a drug context, relative to an alternative reinforcer, in CUD. Supporting the iRISA model, these results elucidate the direct impact of drug-related cue reactivity on the neural signature of inhibitory control in drug addiction.

SUBMITTER: Ceceli AO

PROVIDER: S-EPMC9890460 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Altered prefrontal signaling during inhibitory control in a salient drug context in cocaine use disorder.

Ceceli Ahmet O AO Parvaz Muhammad A MA King Sarah S Schafer Matthew M Malaker Pias P Sharma Akarsh A Alia-Klein Nelly N Goldstein Rita Z RZ

Cerebral cortex (New York, N.Y. : 1991) 20230101 3

<h4>Introduction</h4>Drug addiction is characterized by impaired response inhibition and salience attribution (iRISA), where the salience of drug cues is postulated to overpower that of other reinforcers with a concomitant decrease in self-control. However, the neural underpinnings of the interaction between the salience of drug cues and inhibitory control in drug addiction remain unclear.<h4>Methods</h4>We developed a novel stop-signal functional magnetic resonance imaging task where the stop-s ...[more]

PMID: 35244138

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Project description:ImportanceHeroin addiction and related mortality impose a devastating toll on society, with little known about the neurobiology of this disease or its treatment. Poor inhibitory control is a common manifestation of prefrontal cortex (PFC) impairments in addiction, and its potential recovery following treatment is largely unknown in heroin (or any drug) addiction.ObjectiveTo study inhibitory control brain activity in iHUD and HC, before and after 15 weeks of inpatient treatment in the former.DesignA longitudinal cohort study (11/2020-03/2022) where iHUD and HC underwent baseline and follow-up fMRI scans. Average follow-up duration: 15 weeks.SettingThe iHUD and HC were recruited from treatment facilities and surrounding neighborhoods, respectively.ParticipantsTwenty-six iHUD [40.6±10.1 years; 7 (29.2%) women] and 24 age-/sex-matched HC [41.1±9.9 years; 9 (37.5%) women].InterventionFollowing the baseline scan, inpatient iHUD continued to participate in a medically-assisted program for an average of 15 weeks (abstinence increased from an initial 183±236 days by 65±82 days). The HC were scanned at similar time intervals.Main outcomes and measuresBehavioral performance as measured by the stop-signal response time (SSRT), target detection sensitivity (d', proportion of hits in go vs. false-alarms in stop trials), and brain activity (blood-oxygen level dependent signal differences) during successful vs. failed stops in the stop signal task.ResultsAs we previously reported, at time 1 and as compared to HC, iHUD exhibited similar SSRT but impaired d' [t(38.7)=2.37, p=.023], and lower anterior and dorsolateral PFC (aPFC, dlPFC) activity (p<.001). Importantly, at time 2, there were significant gains in aPFC and dlPFC activity in the iHUD (group*session interaction, p=.002); the former significantly correlated with increases in d' specifically in iHUD (p=.012).Conclusions and relevanceCompared to HC, the aPFC and dlPFC impairments in the iHUD at time 1 were normalized at time 2, which was associated with individual differences in improvements in target detection sensitivity. For the first time in any drug addiction, these results indicate a treatment-mediated inhibitory control brain activity recovery. These neurobehavioral results highlight the aPFC and dlPFC as targets for intervention with a potential to enhance self-control recovery in heroin addiction.

Project description:BackgroundIndividuals with cocaine use disorder experience heightened motivation to pursue rewards tied to cocaine, often triggered by associated cues. Cue reactivity and subsequent craving significantly elevate the risk of substance use, creating a pressing need for treatments that can help alleviate cravings. However, no pharmaceutical therapies for treating cocaine use disorder have been approved. Preclinical findings reveal dysfunctions in the glutamatergic pathway connecting prefrontal regions with the nucleus accumbens, which are correlated with cue-induced substance-seeking behaviour. These alterations, at both molecular and behavioural levels, can be reversed in rodents with N-acetylcysteine, a modulator of glutamatergic signalling. In contrast, the therapeutic potential for humans remains uncertain.MethodsHere, we assessed the impact of a short-term challenge with N-acetylcysteine on neural responses to cocaine cues and cue-induced craving in a randomised, placebo-controlled cross-over trial using a fMRI cue reactivity paradigm. In total, 44 fMRI cue reactivity scans of 22 individuals with cocaine use disorder were recorded-once after the administration of 2,400 mg of N-acetylcysteine/day for 2 days and once after placebo intake.ResultsIn the placebo condition, participants showed increased cue reactivity towards cocaine pictures, accompanied by significantly higher cravings as compared to neutral images. In accordance with recent meta-analyses, cue reactivity was evident in parietal regions such as the posterior cingulate and precuneus, temporal regions like the hippocampus, the bilateral insula, and medial prefrontal regions, namely the inferior, middle, and superior frontal gyrus. Cue-induced activity in the superior frontal gyrus was strongly predicted by the individual duration of cocaine use. While N-acetylcysteine showed no impact on subjectively rated cocaine craving, neural cue reactivity in the superior frontal gyrus was significantly decreased under N-acetylcysteine compared to placebo.ConclusionsOur findings show that prefrontal reactivity to cocaine cues can be reduced even by a brief pharmacological challenge with N-acetylcysteine. Since neural drug cue reactivity has been shown to be a precursor of relapse behaviour, N-acetylcysteine's therapeutic potential should be further investigated in future studies by extending treatment periods.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT02626494.

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Dataset Information

Altered prefrontal signaling during inhibitory control in a salient drug context in cocaine use disorder.

Introduction

Methods

Results

Discussion

Publications

Altered prefrontal signaling during inhibitory control in a salient drug context in cocaine use disorder.

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