It is Never as Good the Second Time Around: Brain Areas Involved in Salience Processing Habituate During Repeated Drug Cue Exposure in Methamphetamine and Opioid Users

AbstractIntroductionThe brain response to drug-related cues is an important marker in addiction-medicine, however, the temporal dynamics of this response in repeated exposure to the cues are not well known yet. In an fMRI drug cue-reactivity task, the presence of rapid habituation or sensitization was investigated by modeling time and its interaction with condition (drug>neutral) using an initial discovery-sample. Replication of this temporal response was tested in two other clinical populations.MethodsSixty-five male participants (35.8±8.4 years-old) with methamphetamine use disorder (MUD) were recruited as the discovery-sample. A linear mixed effects model was used to identify areas with a time-by-condition interaction in the discovery-sample. Replication of these effects was tested in two other samples (29 female with MUD and 22 male with opioid use disorder). The second replication-sample was re-tested within two weeks.ResultsIn the discovery-sample, clusters within the VMPFC, amygdala and ventral striatum showed both significant condition and condition-by-time interaction with a habituation response for the drug-related cues but not neutral cues. The estimates for the main effects and interactions were generally consistent between the discovery and replication-samples across all clusters. The re-test data showed consistent lack of drug>neutral and habituation response within all selected clusters in the second cue-exposure session.ConclusionsVMPFC, amygdala and ventral striatum show a habituation in response to drug-related cues which is consistent among different clinical populations. Habituation in response in the first session of cue-exposure and lack of reactivity in the second session of exposure provide foundations for development of cue-desensitization interventions.

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The role of withdrawal in mesocorticolimbic drug cue reactivity in opioid use disorder

Addiction Biology ◽

10.1111/adb.12977 ◽

2020 ◽

Author(s):

Zhenhao Shi ◽

Kanchana Jagannathan ◽

James H. Padley ◽

An‐Li Wang ◽

Victoria P. Fairchild ◽

...

Keyword(s):

Cue Reactivity ◽

Opioid Use Disorder ◽

Opioid Use ◽

Drug Cue

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How Top-Down and Bottom-Up Regulation in Fronto-Amygdalar Network Changes over Time during Drug Cue-Exposure: An fMRI Study among Abstinent Heroin User

10.1101/678961 ◽

2019 ◽

Author(s):

Arash Zare-Sadeghi ◽

Mohammad Ali Oghabian ◽

Mehran Zare-Bidoky ◽

Seyed Amir Hossein Batouli ◽

Hamed Ekhtiari

Keyword(s):

Regulatory Networks ◽

Cue Reactivity ◽

Network Connectivity ◽

Heroin User ◽

Top Down ◽

Cue Exposure ◽

Down Regulation ◽

Potential Biomarker ◽

Over Time ◽

Drug Cue

AbstractTop-down regulation is one of the major neural cores in drug-craving management and relapse prevention. The dynamic temporal behavior of top-down regulation between the dorso-lateral and ventro-medial prefrontal cortices (DLPFC and VMPFC) and amygdala during drug cue-exposure has not been studied yet. Fifteen abstinent participants with heroin use disorder were scanned using drug cue-induced craving fMRI task. Using Dynamic Causal Modelling (DCM), the winning model showed a significant reciprocal connection between the VMPFC and DLPFC while there was a one-way effect of the VMPFC on the amygdala. There is also a top-down modulation by DLPFC on the VMPFC-Amygdala connection. Craving contrast input only modulated amygdala directly. Using sliding-window for temporal evaluation, craving input to amygdala increased over time, simultaneously, DLPFC top-down modulatory effect on VMPFC-amygdala connection decreased. Temporal changes in the network connectivity during cue exposure with enhancement in craving input to amygdala and reduction in top-down modulatory effects of DLPFC, could provide us with new insights towards the dynamic nature of the cue-reactivity and failure to control its motivational consequences. Dynamic response of top-down regulatory networks during cue exposure can be considered as a new potential biomarker in the future addiction fMRI studies.

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309. The Impact of Addiction Medicine Consultation on Discharges Against Medical Advice in Patients with Opioid Use Disorder and Staphylococcus Aureus Bacteremia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.352 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S152-S152

Author(s):

Stephanie Spivack ◽

Daniel Mueller ◽

Peter Axelrod ◽

Joseph D’Orazio

Keyword(s):

Staphylococcus Aureus ◽

Patient Population ◽

Medical Advice ◽

Index Admission ◽

Opioid Use ◽

Urban Hospital ◽

Addiction Medicine ◽

Against Medical Advice ◽

Number Of Patients ◽

The Impact

Abstract Background People who inject drugs (PWID) are at risk for infectious complications of their injection practices, including Staphylococcus aureus (SA) bacteremia. Prolonged hospitalization is sometimes required; however, rates of discharges against medical advice (AMA) are elevated in this patient population. Inadequate control of pain and opioid withdrawal are commonly cited. Our aim was to assess the effectiveness of addiction medicine consultation for preventing AMA discharges. Methods We performed a retrospective chart review of adult PWID admitted to an urban hospital with SA bacteremia between August 2016 and May 2018. Demographics, HIV and HCV status, and presence or absence of addiction medicine consultation were recorded. We assessed whether discharges were planned or AMA; the number of hospitalizations at 30 days, 90 days, and 1 year from index admission; and death within one year. EpiInfo6 was used for data analysis. Results A total of 360 patients with SA bacteremia were reviewed. Of these, 101 reported intravenous opioid use at admission. Average age was 37 years, and 64% were male. HIV and HCV were present in 13% and 82% of patients, respectively. Addiction medicine was consulted on 29 patients. Of these, 4/29 (13.8%) left AMA, compared to 27/72 (37.5%) of patients without an addiction consult (RR = 0.3678 [95% CI = 0.1412 - 0.9583], p = 0.02). Patients receiving addiction medicine consultation averaged 0.17 readmissions within 30 days of their index admission, compared to 0.39 readmissions in the group without addiction medicine consult (p = 0.27). Readmissions at 90 days and 1 year were also lower but not statistically significant. At 1 year, 6 deaths were observed; 2 who had addiction medicine consultation and 4 who did not. Conclusion Consultation with an addiction medicine specialist significantly reduced the number of patients discharged AMA in a high-risk cohort of PWID presenting with SA bacteremia. Numerically fewer readmissions occurred after consultation, though this difference was not statistically significant. Mortality in both groups was low. There were high rates of HIV and HCV in this patient population, suggesting a particularly vulnerable patient population, which warrants further study. Disclosures All Authors: No reported disclosures

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Transcranial Direct Current Stimulation to Modulate fMRI Drug Cue Reactivity in Methamphetamine Users: A Randomized Clinical Trial

10.1101/2021.04.12.21255366 ◽

2021 ◽

Author(s):

Hamed Ekhtiari ◽

Ghazaleh Soleimani ◽

Rayus Kuplicki ◽

Hung-Wen Yeh ◽

Yoon-Hee Cha ◽

...

Keyword(s):

Clinical Trial ◽

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Cue Reactivity ◽

Methamphetamine Use ◽

Sham Stimulation ◽

Group Time ◽

Methamphetamine Use Disorder ◽

The Brain ◽

Drug Cue

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.

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CRAVING IN THE LAB: STUDIES OF DRUG CUE REACTIVITY

Psychophysiology ◽

10.1111/j.1469-8986.2008.00732.x ◽

2008 ◽

Vol 45 ◽

pp. S6-S7

Keyword(s):

Cue Reactivity ◽

Drug Cue

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Eating behavior in response to food-cue exposure: Examining the cue-reactivity and counteractive-control models.

Psychology of Addictive Behaviors ◽

10.1037/a0013610 ◽

2009 ◽

Vol 23 (1) ◽

pp. 131-139 ◽

Cited By ~ 40

Author(s):

Jennifer S. Coelho ◽

Anita Jansen ◽

Anne Roefs ◽

Chantal Nederkoorn

Keyword(s):

Eating Behavior ◽

Cue Reactivity ◽

Cue Exposure ◽

Control Models

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Cue Exposure for Binge Eating

Exposure Therapy for Eating Disorders ◽

10.1093/med-psych/9780190069742.003.0011 ◽

2019 ◽

pp. 121-130

Author(s):

Carolyn Black Becker ◽

Nicholas R. Farrell ◽

Glenn Waller

Keyword(s):

Binge Eating ◽

Cue Reactivity ◽

Cue Exposure ◽

Food Cravings ◽

Subsequent Response ◽

Do So

Many patients who have experienced difficulties with binge eating continue to do so even after nutritional stabilization. This can happen because they experience learned cues that trigger strong food cravings. Cue exposure can be useful to address such binge eating. This technique involves confronting the cues that typically elicit heightened food cue reactivity (i.e., cravings), while preventing the subsequent response of bingeing. In this process, patients learn that their binge cues are no longer predictive of an actual episode of binge eating. That learning has the effect of substantially weakening cravings that occur in association with exposure to binge eating cues.

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Addiction Medicine Consultations Reduce Readmission Rates for Patients With Serious Infections From Opioid Use Disorder

Clinical Infectious Diseases ◽

10.1093/cid/ciy924 ◽

2018 ◽

Vol 68 (11) ◽

pp. 1935-1937 ◽

Cited By ~ 44

Author(s):

Laura R Marks ◽

Satish Munigala ◽

David K Warren ◽

Stephen Y Liang ◽

Evan S Schwarz ◽

...

Keyword(s):

Opioid Use Disorder ◽

Opioid Use ◽

Addiction Medicine ◽

Readmission Rates ◽

Serious Infections

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Weaker Memory Performance Exacerbates Stress-Induced Cannabis Craving in Youths’ Daily Lives

Clinical Psychological Science ◽

10.1177/2167702619841976 ◽

2019 ◽

Vol 7 (5) ◽

pp. 1094-1108 ◽

Cited By ~ 3

Author(s):

Robert Miranda ◽

Stephanie E. Wemm ◽

Hayley Treloar Padovano ◽

Ryan W. Carpenter ◽

Noah N. Emery ◽

...

Keyword(s):

Working Memory ◽

Real World ◽

Substance Misuse ◽

Memory Performance ◽

Laboratory Data ◽

Cue Exposure ◽

Moment Stress ◽

Daily Lives ◽

Ecological Momentary ◽

Drug Cue

Theories of addiction posit that stimuli associated with drug use, including both exteroceptive (e.g., paraphernalia) and interoceptive (e.g., feeling tense or stressed), evoke craving and contribute to the pathogenesis of substance misuse. Control over drug cue response and stress is essential for moderating use. Building from laboratory data supporting associations between cue exposure, stress, and craving, this study tested whether these associations generalize to real-world settings and examined whether a well-vetted neurocognitive control capacity (i.e., working memory, or WM) moderated associations. Youths ( N = 85; 15–24 years old) completed baseline and ecological momentary assessments. Cue exposure and participants’ average stress predicted higher craving. Youths with weaker WM experienced stronger craving at higher-stress moments but not when faced with cues. Interactions were present for both previous-moment and same-moment stress. Craving among adolescents with stronger WM was not swayed by momentary stress. Findings suggest that stronger WM protects against craving at more stressful moments.

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