Neural circuitry of impaired emotion regulation in substance use disorders
Open accessAbstract
Impaired emotion regulation contributes to the development and severity of substance use disorders (substance disorders). This review summarizes the literature on alterations in emotion regulation neural circuitry in substance disorders, particularly in relation to disorders of negative affect (without substance disorder), and it presents promising areas of future research. Emotion regulation paradigms during functional magnetic resonance imaging are conceptualized into four dimensions: affect intensity and reactivity, affective modulation, cognitive modulation, and behavioral control. The neural circuitry associated with impaired emotion regulation is compared in individuals with and without substance disorders, with a focus on amygdala, insula, and prefrontal cortex activation and their functional and structural connectivity. Hypoactivation of the rostral anterior cingulate cortex/ventromedial prefrontal cortex (rACC/vmPFC) is the most consistent finding across studies, dimensions, and clinical populations (individuals with and without substance disorders). The same pattern is evident for regions in the cognitive control network (anterior cingulate and dorsal and ventrolateral prefrontal cortices) during cognitive modulation and behavioral control. These congruent findings are possibly related to attenuated functional and/or structural connectivity between the amygdala and insula and between the rACC/vmPFC and cognitive control network. Although increased amygdala and insula activation is associated with impaired emotion regulation in individuals without substance disorders, it is not consistently observed in substance disorders. Emotion regulation disturbances in substance disorders may therefore stem from impairments in prefrontal functioning, rather than excessive reactivity to emotional stimuli. Treatments for emotion regulation in individuals without substance disorders that normalize prefrontal functioning may offer greater efficacy for substance disorders than treatments that dampen reactivity.
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Changes in connectivity between specific structures involved in fronto-striatal circuits (e.g., amygdala-medial PFC connectivity) appear important in explaining emotion dysregulation in substance-use disorders.
“Changes in connectivity between speci fi c structures involved in fronto-striatal circuits (e.g., connectivity between amygdala and medial PFC) appear important in explaining emotion dysregulation in substance-use disorders (Koob, 2015; Wilcox et al., 2016).”
From The Interaction of Person-Affect-Cognition-Execution (I-PACE) model for addictive behaviors: Update, generalization to addictive behaviors beyond internet-use disorders, and specification of the process character of addictive behaviors (2019) · cites this paper as Wilcox et al., 2016
The Resting State Functional and Structural Connectivity section reports weaker amygdala–rACC/vmPFC connectivity in substance-use disorders, and Routes of Dysfunction says impaired amygdala–PFC connectivity may contribute to emotion dysregulation. The paper does not characterize that connection as fronto-striatal; its Limitations and Future Work section says the striatum was not a focus of the review. (LLM, conf=0.85)
Experimental — accuracy not yet measuredWhen mental illness diagnoses such as PTSD and substance use disorders co-occur with mTBI, they likely have an additive effect on brain functioning in the VMPFC, further worsening negative urgency impulsivity.
“Therefore, it is likely that when mental illness diagnoses such as PTSD and substance use disorders co-occur with mTBI, they have an additive effect on brain functioning in the VMPFC, further worsening negative urgency impulsivity [69,70].”
From Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial (2024) · cites this paper as [70]
The Routes of Dysfunction section (page unavailable) reports reduced rACC/vmPFC activation in substance use disorders and describes reduced activation in some disorders including PTSD. But Limitations and Future Work (page unavailable) says the impact of comorbid psychiatric disorders on neural circuitry could not be assessed. The paper does not establish an additive effect with mTBI or a resulting worsening of negative urgency impulsivity. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNeuroimaging studies of individuals diagnosed with PTSD and substance use disorder demonstrate diminished volume and hypoactivity in the VMPFC.
“Moreover, neuroimaging studies of individuals diagnosed with PTSD and substance use disorder (2 conditions that are also associated with impulsive behavior and SI) demonstrate diminished volume and hypoactivity in the VMPFC [69,70].”
From Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial (2024) · cites this paper as [70]
The fMRI sections report reduced rACC/vmPFC activation in substance use disorders and describe hypoactivation in PTSD. They do not report diminished vmPFC volume or establish both findings in people diagnosed with both conditions. The Limitations section says the review could not assess the impact of comorbid PTSD on substance-use findings; page numbers were not provided in our copy. (LLM, conf=0.88)
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References 123 · Cited by 213
- Authors
- Wilcox, C. E., Pommy, J. M., & Adinoff, B.
- Affiliations
- University of New Mexico (US)
- Venue
- American Journal of Psychiatry
- Published
- 2016-04-01
- Volume
- 173
- Issue
- 4
- Pages
- 344-361
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC4979988
- OpenAlex
- W2236170483
- Cited by
- 213
- References
- 123
- Citations by year
- 2026: 18 · 2025: 22 · 2024: 15 · 2023: 33 · 2022: 22 · 2021: 18 · 2020: 23 · 2019: 21 · 2018: 20 · 2017: 18 · 2016: 3
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5k23aa021156-05)
- National Institute on Alcohol Abuse and Alcoholism (K23‐AA021156)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- emotion regulation, substance use disorders, neural circuits, rostral anterior cingulate cortex, ventromedial prefrontal cortex, amygdala, insula, cognitive control network, functional connectivity, structural connectivity, emotional modulation, cognitive modulation, behavioral control, prefrontal cortex dysfunction
- MeSH terms
- Self-Control, Affect, Amygdala, Brain, Brain Mapping, Cerebral Cortex, Cognition, Emotions, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Neural Pathways, Prefrontal Cortex, Substance-Related Disorders, Functional Neuroimaging
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