Dysfunctional amygdala activation and connectivity with the prefrontal cortex in current cocaine users

Crunelle, Cleo L.; Kaag, Anne Marije; Munkhof, Hanna E. van den; Reneman, Liesbeth; Homberg, Judith R.; Sabbe, Bernard; Brink, Wim van den; Wingen, Guido van

doi:10.1002/hbm.22913

Cited by 25 publications

(18 citation statements)

References 26 publications

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“…In addition, medial prefrontal-amygdala circuits involved in fear conditioning and extinction have been implicated in persistent drug-seeking behavior and relapses (Crunelle et al 2015 ; Peters et al 2009 ). Interestingly, ventral striatal (VS) high frequency DBS in rats, comparable to the settings often used in humans, impaired extinction training of morphine seeking, whereas low frequency dorsal VS DBS strengthened morphine extinction memory (Martínez-Rivera et al 2016 ).…”

Section: Resultsmentioning

confidence: 99%

Efficacy of Invasive and Non-Invasive Brain Modulation Interventions for Addiction

et al. 2018

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It is important to find new treatments for addiction due to high relapse rates despite current interventions and due to expansion of the field with non-substance related addictive behaviors. Neuromodulation may provide a new type of treatment for addiction since it can directly target abnormalities in neurocircuits. We review literature on five neuromodulation techniques investigated for efficacy in substance related and behavioral addictions: transcranial direct current stimulation (tDCS), (repetitive) transcranial magnetic stimulation (rTMS), EEG, fMRI neurofeedback and deep brain stimulation (DBS) and additionally report on effects of these interventions on addiction-related cognitive processes. While rTMS and tDCS, mostly applied at the dorsolateral prefrontal cortex, show reductions in immediate craving for various addictive substances, placebo-responses are high and long-term outcomes are understudied. The lack in well-designed EEG-neurofeedback studies despite decades of investigation impedes conclusions about its efficacy. Studies investigating fMRI neurofeedback are new and show initial promising effects on craving, but future trials are needed to investigate long-term and behavioral effects. Case studies report prolonged abstinence of opioids or alcohol with ventral striatal DBS but difficulties with patient inclusion may hinder larger, controlled trials. DBS in neuropsychiatric patients modulates brain circuits involved in reward processing, extinction and negative-reinforcement that are also relevant for addiction. To establish the potential of neuromodulation for addiction, more randomized controlled trials are needed that also investigate treatment duration required for long-term abstinence and potential synergy with other addiction interventions. Finally, future advancement may be expected from tailoring neuromodulation techniques to specific patient (neurocognitive) profiles.

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Section: Resultsmentioning

confidence: 99%

Efficacy of Invasive and Non-Invasive Brain Modulation Interventions for Addiction

et al. 2018

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“…Several cue reactivity studies have indeed demonstrated increased amygdala activation in response to substance-related cues, supporting the role of the amygdala in drug-related behavior ( 37 – 39 ). However, we have recently demonstrated that the amygdala in regular cocaine users is also hyperresponsive to negative emotional stimuli in general ( 40 , 41 ), which is suggested to be normalized by substance intake ( 42 ). However, it is still unclear how the amygdala modulates frontostriatal processing of drug-related cues and how this is related to childhood trauma and negative emotional states.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Amygdala-Striatal Functional Connectivity during the Processing of Cocaine Cues in Male Cocaine Users with a History of Childhood Trauma

et al. 2018

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Background and aimsChildhood trauma is associated with increased levels of anxiety later in life, an increased risk for the development of substance use disorders, and neurodevelopmental abnormalities in the amygdala and frontostriatal circuitry. The aim of this study was to investigate the (neurobiological) link among childhood trauma, state anxiety, and amygdala-frontostriatal activity in response to cocaine cues in regular cocaine users.MethodsIn this study, we included 59 non-treatment seeking regular cocaine users and 58 non-drug using controls. Blood oxygenation level-dependent responses were measured using functional magnetic resonance imaging while subjects performed a cue reactivity paradigm with cocaine and neutral cues. Psychophysiological interaction analyses were applied to assess functional connectivity between the amygdala and other regions in the brain. Self-report questionnaires were used to measure childhood trauma, state anxiety, drug use, drug use severity, and craving.ResultsNeural activation was increased during the presentation of cocaine cues, in a widespread network including the frontostriatal circuit and amygdala in cocaine users but not in controls. Functional coupling between the amygdala and medial prefrontal cortex was reduced in response to cocaine cues, in both cocaine users and controls, which was further diminished with increasing state anxiety. Importantly, amygdala-striatal connectivity was positively associated with childhood trauma in regular cocaine users, while there was a negative association in controls. At the behavioral level, state anxiety was positively associated with cocaine use severity and craving related to negative reinforcement.ConclusionChildhood trauma is associated with enhanced amygdala-striatal connectivity during cocaine cue reactivity in regular cocaine users, which may contribute to increased habit behavior and poorer cognitive control. While we cannot draw conclusions on causality, this study provides novel information on how childhood trauma may contribute to the development and persistence of cocaine use disorder.

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“…Participants performed an emotional face matching task, known to probe amygdala and hippocampus activity [31,32]. The block design consisted of the alternated presentation of 2 emotional condition blocks (fearful and angry face expressions) with 3 control condition blocks (blurred ellipses).…”

Section: Fmri Assessment: Emotional Face Matching Taskmentioning

confidence: 99%

Influence of Gamma-Hydroxybutyric Acid-Use and Gamma-Hydroxybutyric Acid-Induced Coma on Affect and the Affective Network

et al. 2019

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Background: Gamma-hydroxybutyric acid (GHB) is a drug of abuse associated with increased emergency room attendances, due to GHB-induced comas. Withdrawal from GHB often increases social anxiety and is linked to alterations in emotion processing. However, little is known about the effects of GHB-use and GHB-induced comas on affect regulation in humans. Objectives: We aimed to assess the effect of GHB-use and GHB-induced comas on the affective network. Method: We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without a GHB-induced coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants completed self-report questionnaires assessing negative affect (depression, anxiety and stress) and performed an emotional face matching task during functional magnetic resonance imaging to probe activity of the amygdala and the hippocampus. Results: The GHB-Coma group reported higher levels of depression, anxiety, and stress; showed decreased activity of the hippocampus; and increased functional connectivity of the left hippocampus with the left fusiform gyrus and a cluster on the left temporal-parietal-occipital junction, when compared with the 2 other groups. The GHB-NoComa group showed decreased functional connectivity of the left hippocampus with the amygdala in comparison with the No-GHB group. Conclusions: GHB-use but in particular GHB-induced comas, are associated with altered emotion identification and hippocampal functioning. Awareness campaigns are required to raise consciousness about the adverse effects of GHB-induced comas on affect regulation, despite the absence of subjective side effects.

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Dysfunctional amygdala activation and connectivity with the prefrontal cortex in current cocaine users

Cited by 25 publications

References 26 publications

Efficacy of Invasive and Non-Invasive Brain Modulation Interventions for Addiction

Efficacy of Invasive and Non-Invasive Brain Modulation Interventions for Addiction

Enhanced Amygdala-Striatal Functional Connectivity during the Processing of Cocaine Cues in Male Cocaine Users with a History of Childhood Trauma

Influence of Gamma-Hydroxybutyric Acid-Use and Gamma-Hydroxybutyric Acid-Induced Coma on Affect and the Affective Network

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