Neural substrates of cue reactivity: association with treatment outcomes and relapse

Courtney, Kelly E.; Schacht, Joseph P.; Hutchison, Kent E.; Roche, Daniel; Ray, Lara A.

doi:10.1111/adb.12314

Cited by 197 publications

(172 citation statements)

References 115 publications

(139 reference statements)

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“…fMRI cue-reactivity paradigms represent an ideal platform to probe the involvement of neurobiological pathways subserving the incentive salience system in addiction (Courtney et al, 2016;Ray et al, in press). Given that BOLD measures of drug cue-reactivity have been shown to predict relapse propensity in treatment seeking patients (eg, Beck et al, 2012;Kosten et al, 2006;Schacht et al, 2013b), the investigation of neurochemical systems that alter BOLD measures of cue-reactivity has the potential to improve real-world clinical outcomes in addiction.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans

Courtney

Ghahremani

Ray

2016

Neuropsychopharmacol

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Interactions between dopaminergic and opioidergic systems have been implicated in the reinforcing properties of drugs of abuse. The present study investigated the effects of opioid blockade, via naltrexone, on functional magnetic resonance imaging (fMRI) measures during methamphetamine cue-reactivity to elucidate the role of endogenous opioids in the neural systems underlying drug craving. To investigate this question, non-treatment seeking individuals with methamphetamine use disorder (N = 23; 74% male, mean age = 34.70 (SD = 8.95)) were recruited for a randomized, placebo controlled, within-subject design and underwent a visual methamphetamine cue-reactivity task during two blood-oxygen-level dependent (BOLD) fMRI sessions following 3 days of naltrexone (50 mg) and matched time for placebo. fMRI analyses tested naltrexone-induced differences in BOLD activation and functional connectivity during cue processing. The results showed that naltrexone administration reduced cue-reactivity in sensorimotor regions and related to altered functional connectivity of dorsal striatum, ventral tegmental area, and precuneus with frontal, visual, sensory, and motor-related regions. Naltrexone also weakened the associations between subjective craving and precuneus functional connectivity with sensorimotor regions and strengthened the associations between subjective craving and dorsal striatum and precuneus connectivity with frontal regions. In conclusion, this study provides the first evidence that opioidergic blockade alters neural responses to drug cues in humans with methamphetamine addiction and suggests that naltrexone may be reducing drug cue salience by decreasing the involvement of sensorimotor regions and by engaging greater frontal regulation over salience attribution.

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Section: Discussionmentioning

confidence: 99%

The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans

Courtney

Ghahremani

Ray

2016

Neuropsychopharmacol

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“…Participants are shown drug-related cues (often pictorial) that are known to induce craving and reward-related brain activation patterns inside the fMRI. The fMRI scanner captures the blood oxygenation level-dependent (BOLD) response, a measure of brain activation (e.g., Courtney et al 2016). Key brain areas that are activated in drug-users in cue reactivity paradigms are the NAc, medial PFC (mPFC), basolateral amygdala and other PFC areas (for reviews, see Courtney et al 2016;Schacht et al 2013).…”

Section: Neuroimaging Techniquesmentioning

confidence: 99%

“…The fMRI scanner captures the blood oxygenation level-dependent (BOLD) response, a measure of brain activation (e.g., Courtney et al 2016). Key brain areas that are activated in drug-users in cue reactivity paradigms are the NAc, medial PFC (mPFC), basolateral amygdala and other PFC areas (for reviews, see Courtney et al 2016;Schacht et al 2013). The NAc, mPFC and amygdala have been associated with bottom-up motivational aspects of cue reactivity (Barros-Loscertales et al 2011), reward processing (Koob and Volkow 2010), subjective drug craving and relapse (Beck et al 2012;Sinha 2012;Volkow et al 2004), whereas the dorsolateral PFC (dlPFC) is involved in top-down control over motivational reactions to drug cues in addiction (Baler and Volkow 2006;Bechara 2005;Sinha 2012).…”

Section: Neuroimaging Techniquesmentioning

confidence: 99%

“…This apparent discrepancy in results is likely to reflect the different temporal resolution for PET metabolic measures (30 min) and fMRI (2-5 min) and are consistent with impairment in control capacity following exposure to cues for which females appear to be more vulnerable than males . Various studies have focused on cue reactivity and relapse (recently reviewed in Courtney et al 2016). For example, alcohol cue-induced activation in the mPFC was elevated in alcoholics versus controls (Beck et al 2012).…”

Section: Neuroimaging Techniquesmentioning

confidence: 99%

“…Several studies involving different drugs of abuse, including alcohol, nicotine and cocaine, have shown consistent brain areas of increased activation in drug abusers when they view cues of their drug. In addition, pharmacological agents that block dopamine release can erase the increased activation of these cue-craving areas (Courtney et al 2016).…”

Section: Neural Effects Of Pharmacological Interventionsmentioning

confidence: 99%

See 2 more Smart Citations

Neuroimaging the Effectiveness of Substance Use Disorder Treatments

Cabrera

Wiers

Lindgren

et al. 2016

J Neuroimmune Pharmacol

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Neuroimaging techniques to measure the function and biochemistry of the human brain such as positron emission tomography (PET), proton magnetic resonance spectroscopy ((1)H MRS), and functional magnetic resonance imaging (fMRI), are powerful tools for assessing neurobiological mechanisms underlying the response to treatments in substance use disorders. Here, we review the neuroimaging literature on pharmacological and behavioral treatment in substance use disorder. We focus on neural effects of medications that reduce craving (e.g., naltrexone, bupropion hydrochloride, baclofen, methadone, varenicline) and that improve cognitive control (e.g., modafinil, N-acetylcysteine), of behavioral treatments for substance use disorders (e.g., cognitive bias modification training, virtual reality, motivational interventions) and neuromodulatory interventions such as neurofeedback and transcranial magnetic stimulation. A consistent finding for the effectiveness of therapeutic interventions identifies the improvement of executive control networks and the dampening of limbic activation, highlighting their values as targets for therapeutic interventions in substance use disorders.

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Association of Neural Responses to Drug Cues With Subsequent Relapse to Stimulant Use

et al. 2018

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Importance Although chronic relapse is a characteristic of addiction to stimulants, conventional measures (eg, clinical, demographic, and self-report) do not robustly identify which individuals are most vulnerable to relapse. Objectives To test whether drug cues are associated with increased mesolimbic neural activity in patients undergoing treatment for stimulant use disorder and whether this activity is associated with risk for subsequent relapse. Design, Setting, and Participants This prospective cohort study of 76 participants included a control group for baseline group comparisons. Veteran patients (n = 36) with stimulant use disorders were recruited from a 28-day residential treatment program at the Veterans Affairs Palo Alto Health Care System. Healthy controls (n = 40) were recruited from the surrounding community. Baseline data were collected between September 21, 2015, and January 26, 2018, from patients and healthy controls using functional magnetic resonance imaging during a performance of a reward cue task. Patients’ stimulant use was subsequently assessed after treatment discharge (at approximately 1, 3, and 6 months) to assess relapse outcomes. Main Outcomes and Measures Primary measures included neural responses to drug and food cues in estimated mesolimbic volumes of interest, including the medial prefrontal cortex, nucleus accumbens (NAcc), and ventral tegmental area. The primary outcome variable was relapse (defined as any stimulant use), assessed both dichotomously (3 months after discharge) and continuously (days to relapse). Brain activity measures were contrasted between groups to validate neural measures of drug cue reactivity, which were then used to estimate relapse outcomes of patients. Results Relative to controls (n = 40; 16 women and 24 men; mean [SD] age, 32.0 [11.6] years), patients (n = 36; 2 women and 34 men; mean [SD] age, 43.4 [13.3] years) showed increased mesolimbic activity in response to drug cues (medial prefrontal cortex, t 74 = 2.90, P = .005, Cohen d = 0.66; NAcc, t 74 = 2.39, P = .02, Cohen d = 0.54; and ventral tegmental area, t 74 = 4.04, P < .001, Cohen d = 0.92). In patients, increased drug cue response in the NAcc (but not other volumes of interest) was associated with time to relapse months later (Cox proportional hazards regression hazard ratio, 2.30; 95% CI, 1.40-3.79). After controlling for age, NAcc response to drug cues classified relapsers (12 patients; 1 woman and 11 men; mean [SD] age, 49.3 [14.1] years) and abstainers (21 patients; 1 woman and 20 men; mean [SD] age, 39.3 [12.3] years) at 3 months with 75.8% classification accuracy. Model com...

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Neural substrates of cue reactivity: association with treatment outcomes and relapse

Cited by 197 publications

References 115 publications

The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans

The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans

Neuroimaging the Effectiveness of Substance Use Disorder Treatments

Association of Neural Responses to Drug Cues With Subsequent Relapse to Stimulant Use

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