Drug cue reactivity as a possible “severity” dimension in cocaine dependence

1992 ◽  
Vol 42 (2) ◽  
pp. 367
2021 ◽  
Author(s):  
Hamed Ekhtiari ◽  
Ghazaleh Soleimani ◽  
Rayus Kuplicki ◽  
Hung-Wen Yeh ◽  
Yoon-Hee Cha ◽  
...  

Transcranial direct current stimulation (tDCS) has been studied as an adjunctive therapeutic option to alter maladaptive cortical excitability, activity, and connectivity associated with chronic substance use via the application of a weak direct current through the brain. The underlying mechanism of action remains ambiguous, however. We present a randomized, triple-blind, sham-controlled, clinical trial with two parallel arms conducted to determine the neural substrates of tDCS effects on drug craving using an fMRI drug cue reactivity paradigm. Sixty participants with methamphetamine use disorder were randomly assigned to two groups: 30 participants to active tDCS (5x7 cm2, 2 mA, for 20 minutes, anode/cathode over the F4/Fp1 in EEG 10-20 standard system) and 30 participants to the sham group. Neuroimaging data of a methamphetamine cue reactivity (MCR) task were collected immediately before and after stimulation with subjective craving assessed before, after, and during fMRI scans. There was a significant reduction in self-reported craving after stimulation (main effect of time) without any significant effect of group, time, or by group-time interaction. Our whole-brain analysis demonstrated that brain activation decreased in all parts of the brain in the second (post-stimulation) MCR imaging session after sham stimulation (habituation) but this uniform decrease did not occur throughout the brain in the active group. There were significant interactions between the group (active vs. sham) and time (after vs. before stimulation) in five main regions; medial frontal gyrus, anterior insula, inferior parietal lobule, precuneus, and inferior frontal gyrus with higher activations after active stimulation. We simulated computational head models for each individual. There was a significant effect of group in the relationship between level of current in the above-mentioned significant clusters and changes in task-modulated activation. We also found that brain regions with the highest electric fields in the prefrontal cortex showed a significant time by group interaction in task-modulated connectivity (psychophysiological interaction during MCR) in the frontoparietal network. In this two-parallel-arms triple-blind randomized control trial, we did not find any significant effect of the one session of active F4/Fp1 tDCS on drug craving self-report compared to sham stimulation. However, connectivity differences induced by active compared to sham stimulation suggested some potential mechanisms of tDCS to modulate neural response to drug cues among people with methamphetamine use disorder.


2020 ◽  
Author(s):  
Zhenhao Shi ◽  
Kanchana Jagannathan ◽  
James H. Padley ◽  
An‐Li Wang ◽  
Victoria P. Fairchild ◽  
...  

2021 ◽  
Author(s):  
Ahmet O. Ceceli ◽  
Muhammad A. Parvaz ◽  
Sarah King ◽  
Matthew Schafer ◽  
Pias Malaker ◽  
...  

AbstractDrug 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. We developed a novel stop-signal fMRI 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) vs. demographically matched healthy control participants (HC; n=26). Despite similarities in drug cue-related SSRT and valence and arousal word ratings between groups, the 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 < .05 corrected). Results suggest reduced 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.Significance statementExcessive salience attribution to drugs and related cues at the expense of nondrug reinforcers and cues and inhibitory control impairments are hallmark symptoms of drug addiction. Although these neuropsychological functions have been investigated independently, brain representations of their interaction are less clear. We illustrate that, despite matched behavioral performance and valence and arousal ratings, the dorsolateral prefrontal cortex—a key node of the cognitive control network also associated with craving—exhibits decreased signaling when successfully inhibiting responses to drug compared to nondrug (food) cues (words) in cocaine-addicted individuals. Modulating salience while taxing self-control permits the study of their combined impact, an ecologically valid examination of the addiction experience. Better understanding inhibitory control under drug cue-reactivity may refine targeted neuromodulatory interventions.


2020 ◽  
Author(s):  
Hamed Ekhtiari ◽  
Mehran Zare-Bidoky ◽  
Arshiya Sangchooli ◽  
Amy C. Janes ◽  
Marc J. Kaufman ◽  
...  

AbstractBackgroundCue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been many promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, heterogeneities in participant characteristics, task design, craving assessment, scanning preparation and analysis decisions limit rigor and reproducibility in the field of fMRI of drug cue reactivity (FDCR), hampering clinical translation and synthesis by systematic reviews and meta-analyses. The aim of this consensus paper and Delphi study is to outline the important methodological aspects of FDCR studies and present a list of items and recommendations that should be taken into account when designing FDCR studies and reporting their results.MethodsFifty-five FDCR scientists from around the world participated. First, an initial checklist of items deemed important in FDCR studies was developed by a group of members from the ENIGMA Addiction Consortium based on a systematic review. Then, using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist. Subsequently, experts were asked to rate the importance of the items.ResultsThirty-seven items were proposed in the first round. After the commenting phase, seven new items suggested by experts were added and six were removed. The final 38 items that reached a defined consensus threshold in the rating phase were classified under seven categories and are considered important for conducting and reporting in any FDCR study.ConclusionThis paper proposes a list of items and additional recommendations that researchers in the field of FDCR are encouraged to note and report when designing an FDCR study and reporting its results. Along with the presentation of a quality control checklist with Yes/No ratable items, various challenges in moving towards greater homogeneity in FDCR research and widespread use of FDCR to investigate SUDs and develop clinically relevant biomarkers are discussed.


2010 ◽  
Vol 48 (9) ◽  
pp. 860-865 ◽  
Author(s):  
Kimber L. Price ◽  
Michael E. Saladin ◽  
Nathaniel L. Baker ◽  
Bryan K. Tolliver ◽  
Stacia M. DeSantis ◽  
...  
Keyword(s):  

2016 ◽  
Vol 41 (12) ◽  
pp. 2872-2881 ◽  
Author(s):  
Kelly E Courtney ◽  
Dara G Ghahremani ◽  
Lara A Ray

2021 ◽  
Author(s):  
Ghazaleh Soleimani ◽  
Rayus Kupliki ◽  
Jerzy Bodurka ◽  
Martin Paulus ◽  
Hamed Ekhtiari

AbstractBackgroundFrontoparietal network (FPN) with multiple cortical nodes is involved in executive functions. Transcranial electrical stimulation (tES) can potentially modulate interactions between these nodes using frontoparietal synchronization (FPS). Here we used fMRI and computational head models (CHMs) to inform electrode montage and dosage selection in FPS.MethodsSixty methamphetamine users completed an fMRI drug cue-reactivity task. Two sets of 4×1 HD electrodes with anode over F3 and F4 were simulated and spheres around maximum electric field in each hemisphere were defined as frontal seeds. Using frontal seeds, a task-based functional connectivity analysis was conducted based on a seed-to-whole brain generalized psychophysiological interaction (gPPI). Electrode placement for parietal sites was selected based on gPPI results. Task-based and resting-state connectivity were compared between fMRI-informed and classic F3-P3/F4-P4 montages.ResultsWhole-brain gPPI showed two significant clusters (left: 506 voxels P=0.006, right: 455 voxels P=0.016), located in the inferior parietal lobule under the CP5 and CP6 electrode location. Pair-wise ROI-based gPPI comparing informed (F3-CP5/F4-CP6) and classic (F3-P3/F4-P4) montages showed significant increased PPI and resting-state connectivity only in the informed montage. Cue-induced craving score was also correlated with left (F3-CP5) frontoparietal connectivity in the fMRI-informed montage.ConclusionThis study proposes an analytic pipeline to select electrode montage and dosage in dual site tES using CHMs and task-based connectivity. Stimulating F3-F4 can tap into both FPN and saliency network (SN) based on the montage selection. Using CHM and fMRI will be essential to navigating ample parameter space in the stimulation protocols for future tES studies.HighlightsWe demonstrated a methodology for montage selection in network-based tESTask-based functional connectivity can inform dual-site tES montage selectionHead models can help to induce balance tES dose in targeted brain regionsTargeting DLPFC with tES can tap into both saliency and frontoparietal networksLower resting-state frontoparietal connectivity before cue exposure followed by a greater craving


2021 ◽  
Author(s):  
Amirhossein Dakhili ◽  
Arshiya Sangchooli ◽  
Sara Jafakesh ◽  
Mehran Zare-Bidoky ◽  
Ghazaleh Soleimani ◽  
...  

Background: Drug-related cue-reactivity, dysfunctional negative emotion processing, and response-disinhibition constitute three core aspects of methamphetamine use disorder (MUD). These phenomena have been studied independently, but the neuroscientific literature on their interaction in addictive disorders remains scant. Methods: fMRI data were collected from 62 individuals with MUD when responding to the geometric Go or No-Go cues superimposed over blank, neutral, negative-emotional and drug-related background images. Neural correlates of drug and negative-emotional cue-reactivity, response-inhibition, and response-inhibition during drug and negative-emotional blocks were estimated, and methamphetamine cue-reactivity was compared between MUDs and 23 healthy controls (HCs). Relationships between clinical and behavioral characteristics and observed activations were subsequently investigated. Results: MUDs had longer reaction times and more errors in drug and negative-emotional blocks compared to neutral and blank ones. MUDs showed higher drug cue-reactivity than HCs across prefrontal regions, fusiform gyrus, and visual cortices (Z>3.1, p-corrected<0.05). Response-inhibition was associated with activations in the precuneus, inferior parietal lobule, and anterior cingulate, temporal and inferior frontal gyri (Z>3.1, p-corrected<0.05). Response-inhibition in drug cue blocks coincided with higher activations in the visual cortex and lower activations in the paracentral lobule and superior and inferior frontal gyri, while inhibition during negative-emotional blocks led to higher superior parietal, fusiform, and lateral occipital activations (Z>3.1, p-corrected<0.05). Conclusion: Higher visual cortical activations and lower parietal and prefrontal activations during drug-related response-inhibition suggest the down-regulation of inhibitory regions and up-regulation of bottom-up drug cue-reactivity. Our results suggest that drug and negative-emotional cue-reactivity influence response-inhibition, and the study of these interactions may aid mechanistic understandings of addiction and biomarker discovery.


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