Short communicationAcute alcohol intake alters resting state functional connectivity of nucleus accumbens with pain-related corticolimbic structures
Introduction
The nucleus accumbens (NAc) is a basal forebrain structure with neuroanatomic and functional connections to a range of structures, including medial prefrontal cortex (mPFC), amygdala, and insula (Ikemoto, 2010).The role of the NAc in reinforcement and reward associated with alcohol use is well appreciated (Russo et al., 2010); briefly, alcohol-induced release of dopamine and opioid peptides in the NAc underlie its reinforcing properties (Koob and Volkow, 2010). Chronic pain and alcohol use disorder (AUD) frequently co-occur (e.g., Boissoneault et al., 2019) and involve overlapping neural substrates (Apkarian et al., 2013; Becerra and Borsook, 2008; Egli et al., 2012; Scott et al., 2006; Zale et al., 2015), but empirical studies regarding alcohol effects on resting state functional connectivity (rsFC) between regions and networks relevant to alcohol/pain interactions, including NAc, are lacking.
Previous studies have examined changes in rsFC with acute alcohol administration (e.g., Gorka et al., 2018; Shokri-Kojori et al., 2017). However, acute alcohol effects on NAc-related circuits underlying motivation/reward, pain processing and chronification have not previously been examined. Thus, this study examined the acute effects of alcohol on rsFC between NAc and mPFC. Because alcohol can have analgesic effects in experimental settings (Thompson et al., 2017), and chronic pain is associated with greater rsFC between these structures, we hypothesized that acute alcohol intake would reduce NAc-mPFC connectivity. We also examined alcohol effects on connectivity of NAc with amygdala and insula, given their extensive anatomic and functional connections to the NAc (Ikemoto, 2010) and their role in modulating both alcohol’s reinforcing effects and the pain experience (Koob and Volkow, 2010).
Section snippets
Participants
Community-dwelling healthy drinkers (N = 15; 10 women), 25–45 years of age, were recruited as part of a study regarding biopsychosocial mechanisms underlying alcohol analgesia. Informed consent was obtained prior to data collection. The study was approved by the University of Florida IRB (Protocol #2018-0889).
Screening procedure
During the screening/eligibility session, participants completed questionnaires (demographics; medical history; Beck Depression Inventory-II (BDI-II; Beck et al., 1996); State-Trait
Participant characteristics
Participants averaged 30.8 years of age (SD = 3.7) and 20.1 years of education (SD = 2.87). Mean BDI-II and STAI-trait scores were 3.27 (SD = 3.8) and 29.3 (SD = 7.4), indicating minimal distress. Participants consumed, on average, 0.63 (SD = .37) oz. absolute ethanol/day over the 6 months prior to screening (∼1 standard drink). Maximum single-day consumption during this period averaged 4.68 (SD = 2.05) oz. absolute ethanol (∼8 standard drinks). The mean AUDIT score was 5.1 (SD = 1.8).
BrAC and SAC measures
Mean BrAC
Discussion
Results supported hypotheses that acute alcohol would disrupt NAc-mPFC and NAc-amygdala rsFC. Whole-brain analyses also indicated alcohol-related disruption of NAc-paracingulate/ACC rsFC. Alcohol did not appear to meaningfully affect NAc-insula rsFC.
Alcohol-related reductions in NAc-mPFC connectivity are intriguing given evidence that greater rsFC between these structures is associated with poorer self-regulation of experimental pain (Woo et al., 2015), chronic pain status (Baliki et al., 2010
Contributors
JB and MR designed the study, JB and BS collected data, JB conducted analyses, and JB, BS, and MR wrote the manuscript. All authors approved the final version of the manuscript for submission.
Role of funding source
Support for this work was provided by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under award number R01AA025337. The content of this article is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health.
Declaration of Competing Interest
The authors declare no conflict of interest.
Acknowledgment
The authors wish to thank the participants of this study for their willingness to participate.
References (38)
- et al.
Predicting value of pain and analgesia: nucleus Accumbens response to noxious stimuli changes in the presence of chronic pain
Neuron
(2010) - et al.
Signal valence in the nucleus accumbens to pain onset and offset
Eur. J. Pain
(2008) - et al.
A component based noise correction method (CompCor) for BOLD and perfusion based fMRI
Neuroimage
(2007) - et al.
Characterizing chronic pain and alcohol use trajectory among treatment-seeking alcoholics
Alcohol
(2019) - et al.
Cognitive and emotional influences in anterior cingulate cortex
Trends Cogn. Sci. (Regul. Ed.)
(2000) - et al.
An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest
Neuroimage
(2006) - et al.
Alcohol dependence as a chronic pain disorder
Neurosci. Biobehav. Rev.
(2012) Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory
Neurosci. Biobehav. Rev.
(2010)- et al.
Self-report of alcohol use for pain in a multi-ethnic community sample
J. Pain
(2009) - et al.
The addicted synapse: mechanisms of synaptic and structural plasticity in nucleus accumbens
Trends Neurosci.
(2010)
Analgesic effects of alcohol: a systematic review and meta-analysis of controlled experimental studies in healthy participants
J. Pain
Abnormal cortical activity in patients with temporomandibular disorder evoked by cognitive and emotional tasks
Pain
Interrelations between pain and alcohol: an integrative review
Clin. Psychol. Rev.
Predicting transition to chronic pain
Curr. Opin. Neurol.
Corticostriatal functional connectivity predicts transition to chronic back pain
Nat. Neurosci.
Immediate, quantitative estimation of blood alcohol concentration from saliva
J. Stud. Alcohol
Beck Depression Inventory
Acute effects of moderate alcohol on psychomotor, set shifting, and working memory function in older and younger social drinkers
J. Stud. Alcohol Drugs
Recommended Council Guidelines on Ethyl Alcohol Administration in Human Experimentation Retrieved 8/22, 2014
Cited by (12)
Neural underpinnings of expecting alcohol: Placebo alcohol administration alters nucleus accumbens resting state functional connectivity
2023, Behavioural Brain ResearchCitation Excerpt :These results add to the literature, suggesting NAcc networks may contribute to the subjective experience of intoxication through non-pharmacological, expectancy-related factors. Interestingly, prior studies examining NAcc – PFC resting state functional connectivity following acute alcohol consumption have been mixed, with either decreased or no change in functional connectivity reported [13,14]. Results from the current study indicate the non-pharmacological factors associated with alcohol use may relate to distinct changes in NAcc – ventral PFC networks during rest.
Acute effects of alcohol on resting-state functional connectivity in healthy young men
2021, Addictive BehaviorsCitation Excerpt :Two prior studies found that alcohol reduced fMRI resting-state connectivity involving ventral striatum, but to different regions (Khalili-Mahani et al., 2012; Gorka et al., 2018). In one study alcohol reduced connectivity between the NAcc and the medial prefrontal cortex, amygdala, and anterior cingulate (Boissoneault et al., 2020) whereas the other observed reduced connectivity between ventral striatum and globus pallidus externus (Fede et al.,). Individuals who are frequent drinkers exhibit greater negative functional connectivity between the mPFC and the nucleus accumbens (Forbes, Rodriguez, Musselman, & Narendran, 2014).
Electroencephalography-Based Effects of Acute Alcohol Intake on the Pain Matrix
2023, Brain Sciences