Alcohol-Induced Impairment of Inhibitory Control Is Linked to Attenuated Brain Responses in Right Fronto-Temporal Cortex

Gan, Gabriela; Guevara, Alvaro; Marxen, Michael; Neumann, Maike; Jünger, Elisabeth; Kobiella, Andrea; Mennigen, Eva; Pilhatsch, Maximilian; Schwarz, Daniel; Zimmermann, U.; Smolka, Michael N.

doi:10.1016/j.biopsych.2013.12.017

Cited by 89 publications

(81 citation statements)

References 62 publications

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“…Probably alcohol does not affect evaluation-related medial PFC activity as behavioral provocation effects on aggression and RTs were present under alcohol as well as placebo. In contrast, alcohol decreased brain responses irrespective of provocation in inferior/middle frontal areas possibly reflecting impaired top-down control under alcohol (Heinz et al, 2011;Kareken et al, 2013;Gan et al, 2014).…”

Section: Discussionmentioning

confidence: 89%

“…All study procedures, including alcohol administration, are detailed elsewhere Gan et al, 2014). For the placebo-controlled cross-over design, see Figure 1a.…”

Section: Methodsmentioning

confidence: 99%

“…All participants were physically (eg, no central nervous, cardio-vascular, or liver/kidney disease) and mentally healthy (eg, no previous or current alcohol/illicit drug abuse/dependence), abstained from illicit drugs/alcohol for at least 1 week/24 h before each experimental day, had a positive (FH+, at least one first-degree biological relative affected by alcoholism) or negative (no biological relative affected by alcoholism) family history of alcoholism (FHA; considered as covariate if affecting outcome variables) (for recruitment, detailed inclusion/exclusion criteria: Marxen et al, 2014;Gan et al, 2014). Exclusion criteria were MR-contraindications and pregnancy or breast-feeding in women.…”

Section: Participantsmentioning

confidence: 99%

“…However, people need to control possible outbursts of aggression in everyday life, because most societies will punish and not tolerate overt aggression. Behavioral control of aggression might especially be difficult under the influence of alcohol, a substance that impairs inhibitory control (eg, de Wit et al, 2000;Gan et al, 2014). Indeed, alcohol is involved in about one-half of violent crime, including domestic violence (Bureau of Justice Statistics, 1998;Foran and O'Leary, 2008;Bundeskriminalamt, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, alcohol-induced impairment of inhibitory control has been related to diminished activity of the lateral PFC (Kareken et al, 2013;Gan et al, 2014) and anterior cingulate cortex (ACC) under alcohol (Anderson et al, 2011). Aggressive behavior has also been linked to PFC hypo-activation, especially in the dorsal (d) ACC (Sterzer et al, 2005;Meyer-Lindenberg et al, 2006;Aharoni et al, 2013), and to increased activation of the amygdala, in particular for impulsive aggression triggered by provocation or threat, also referred to as reactive aggression (Meyer-Lindenberg et al, 2006;Coccaro et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation

Gan

Sterzer

Marxen

et al. 2015

Neuropsychopharmacol

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Although alcohol consumption is linked to increased aggression, its neural correlates have not directly been studied in humans so far. Based on a comprehensive neurobiological model of alcohol-induced aggression, we hypothesized that alcohol-induced aggression would go along with increased amygdala and ventral striatum reactivity and impaired functioning of the prefrontal cortex (PFC) under alcohol. We measured neural and behavioral correlates of alcohol-induced aggression in a provoking vs non-provoking condition with a variant of the Taylor aggression paradigm (TAP) allowing to differentiate between reactive (provoked) and proactive (unprovoked) aggression. In a placebo-controlled cross-over design with moderate alcohol intoxication (~0.6 g/kg), 35 young healthy adults performed the TAP during functional magnetic resonance imaging (fMRI). Analyses revealed that provoking vs non-provoking conditions and alcohol vs placebo increased aggression and decreased brain responses in the anterior cingulate cortex/dorso-medial PFC (provokingonon-provoking) and the ventral striatum (alcoholoplacebo) across our healthy sample. Interestingly, alcohol specifically increased proactive (unprovoked) but not reactive (provoked) aggression (alcohol × provocation interaction). However, investigation of inter-individual differences revealed (1) that pronounced alcohol-induced proactive aggression was linked to higher levels of aggression under placebo, and (2) that pronounced alcohol-induced reactive aggression was related to increased amygdala and ventral striatum reactivity under alcohol, providing evidence for their role in human alcohol-induced reactive aggression. Our findings suggest that in healthy young adults a liability for alcohol-induced aggression in a non-provoking context might depend on overall high levels of aggression, but on alcohol-induced increased striatal and amygdala reactivity when triggered by provocation.

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Section: Discussionmentioning

confidence: 89%

“…All study procedures, including alcohol administration, are detailed elsewhere Gan et al, 2014). For the placebo-controlled cross-over design, see Figure 1a.…”

Section: Methodsmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation

Gan

Sterzer

Marxen

et al. 2015

Neuropsychopharmacol

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The regulatory roles of socio‐economic status, social and intellectual activity in the relationship between alcohol consumption and cognitive decline trajectory in middle‐aged and elderly Chinese: A prospective cohort study

Fang

Chen

et al. 2023

Int J Geriat Psychiatry

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Objectives To determine the relationship between alcohol consumption and cognitive decline, and to further explore the potential regulatory role of education, socio‐economic status (SES), and social or intellectual activity in this relationship. Methods 6197 participants aged 45–75 years with four repeated measures data from 2011 to 2018 were included. A mixed‐effect model was used to explore the relationship between alcohol consumption and the rate of change in cognitive decline, a latent class growth mixed model (LCGMM) was applied to determine the potential trajectory of cognitive decline, and finally, the mediating and moderating analyses were used to determine the regulatory effect of all four variables on the relationship between alcohol consumption and potential trajectory. Results Compared to never‐drinkers, moderate alcohol consumption was a protective factor for overall cognitive function (β = 0.13, 95% CI: 0.04–0.20, p < 0.001), but there was no statistical correlation with the decline rate of cognitive function. And this protective effect was no longer significant after additional adjustments for education, SES, social and intellectual activity. The LCGMM model divided participants into two trajectories, a high‐level‐to‐decline group including 79.75% of participants (quadratic: β [SE]: −0.90 [0.07], p < 0.001), and a low‐level‐to‐decline group including 20.25% participants (linear: β [SE]: −3.05 [0.49], p < 0.001). With the latter as the reference, SES played a reverse regulation role in the harmful effect of heavy drinking on cognitive trajectories (odd ratio [OR] = 0.46, 95% CI: 0.23–0.93, p < 0.05). Social and intellectual activities played a negative mediating role in the harmful effect of alcohol consumption on cognitive trajectories (light: OR = 0.96, p < 0.001; moderate: OR = 0.96, p < 0.001; heavy: OR = 0.97, p < 0.01). Conclusions Alcohol itself has no protective effect on the decline of longitudinal cognitive trajectory. But the regulatory effect of SES, social and intellectual activities slows down the harm of alcohol consumption on the decline of cognitive function. Clinical Trial Registration The data used in this study are from publicly available databases. They are retrospective cohort studies without any intervention. Therefore, no clinical trial registration has been conducted.

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The Cerebellar GABAAR System as a Potential Target for Treating Alcohol Use Disorder

Rossi¹,

Richardson²

2018

The Neuropharmacology of Alcohol

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In the brain, fast inhibitory neurotransmission is mediated primarily by the ionotropic subtype of the gamma-aminobutyric acid (GABA) receptor subtype A (GABAR). It is well established that the brain's GABAR system mediates many aspects of neurobehavioral responses to alcohol (ethanol; EtOH). Accordingly, in both preclinical studies and some clinical scenarios, pharmacologically targeting the GABAR system can alter neurobehavioral responses to acute and chronic EtOH consumption. However, many of the well-established interactions of EtOH and the GABAR system have been identified at concentrations of EtOH ([EtOH]) that would only occur during abusive consumption of EtOH (≥40 mM), and there are still inadequate treatment options for prevention of or recovery from alcohol use disorder (AUD, including abuse and dependence). Accordingly, there is a general acknowledgement that more research is needed to identify and characterize: (1) neurobehavioral targets of lower [EtOH] and (2) associated brain structures that would involve such targets in a manner that may influence the development and maintenance of AUDs.Nearly 15 years ago it was discovered that the GABAR system of the cerebellum is highly sensitive to EtOH, responding to concentrations as low as 10 mM (as would occur in the blood of a typical adult human after consuming 1-2 standard units of EtOH). This high sensitivity to EtOH, which likely mediates the well-known motor impairing effects of EtOH, combined with recent advances in our understanding of the role of the cerebellum in non-motor, cognitive/emotive/reward processes has renewed interest in this system in the specific context of AUD. In this chapter we will describe recent advances in our understanding of cerebellar processing, actions of EtOH on the cerebellar GABAR system, and the potential relationship of such actions to the development of AUD. We will finish with speculation about how cerebellar specific GABAR ligands might be effective pharmacological agents for treating aspects of AUD.

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Alcohol-Induced Impairment of Inhibitory Control Is Linked to Attenuated Brain Responses in Right Fronto-Temporal Cortex

Cited by 89 publications

References 62 publications

Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation

Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation

The regulatory roles of socio‐economic status, social and intellectual activity in the relationship between alcohol consumption and cognitive decline trajectory in middle‐aged and elderly Chinese: A prospective cohort study

The Cerebellar GABAAR System as a Potential Target for Treating Alcohol Use Disorder

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