Amygdala and Orbitofrontal Reactivity to Social Threat in Individuals with Impulsive Aggression

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.

Section: Discussioncontrasting

confidence: 79%

Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

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Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation

Gan

Sterzer

Marxen

et al. 2015

“…In an fMRI study on face processing, Coccaro et al (2007) found a stronger amygdala response to angry faces in IED compared with controls, and a correlation between amygdala activation and a life history of aggression. Moreover, IED patients showed less amygdala-orbitofrontal cortex connectivity than controls, suggesting reduced regulatory control of the prefrontal cortex.…”

Section: Introductionmentioning

confidence: 99%

Effects of Escitalopram Administration on Face Processing in Intermittent Explosive Disorder: An fMRI Study

Cremers

Lee

Keedy

et al. 2015

The neurobiological underpinnings of intermittent explosive disorder (IED) are traditionally linked to deficiencies in the serotonergic system. In this study, we investigated the effects of escitalopram, a selective serotonin reuptake inhibitor (SSRI), on brain activation during face processing. We expected that escitalopram would reduce amygdala activity in IED and in addition, we explored the effect in other social-emotional-related brain regions. A total of 17 subjects with current IED and 14 healthy controls participated in a randomized, double-blind, placebo-controlled, counterbalanced fMRI face processing study. The analysis focused on the faces compared to a fixation baseline contrast, and a factorial model with Group as between-subject and Drug as within-subject factor was tested. Group × Drug interaction effects were found in the amygdala (small volume corrected) and the left temporal parietal junction (TPJ; whole-brain corrected). Escitalopram increased amygdala activation in controls, but surprisingly not in IED. However, the TPJ showed increased activity in IED on escitalopram compared with placebo. The TPJ is associated with social-cognitive processes, such as perspective taking and empathy. The TPJ findings suggest that SSRI administration may reduce aggressive tendencies towards other people by enhancing these social-cognitive processes. Future research should further elucidate the long-term effects of SSRIs on various social-emotional tasks in IED.

“…On the molecular level, serotonergic (Coccaro et al, 2015), neuropeptide (Coccaro et al, 1998), and inflammatory protein abnormalities have been linked to impulsive aggression. At the macro level, functional brain imaging studies have found evidence of exaggerated amygdala response to angry faces and diminished functional connectivity between the amygdala and orbitofrontal cortex (Coccaro et al, 2007). Impulsive aggression has been associated with abnormal patterns of task-related functional brain activity, with enhanced blood oxygen level-dependent (BOLD) activity in the amygdala and orbitofrontal cortex during provoked aggression but lower parietal activity in the medial parietal regions (New et al, 2009); enhanced amygdala BOLD reactivity to neutral faces (Bobes et al, 2013); lower striatal metabolic activity in both provoked and nonprovoked aggression as measured by FDG-PET in males (Perez-Rodriguez et al, 2012); and higher error-related dorsolateral prefrontal cortex BOLD activity (Moeller et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

White Matter Integrity Reductions in Intermittent Explosive Disorder

Lee

Arfanakis

Evia

et al. 2016

Intermittent explosive disorder (IED), as described in DSM-5, is the categorical expression of pathological impulsive aggression. Previous work has identified neurobiological correlates of the disorder in patterns of frontal-limbic brain activity and dysregulation of serotonergic neurotransmission. Given the importance of short-and-long range white matter connections of the brain in social and emotional behavior, studies of white matter connectivity in impulsive aggression are warranted. Diffusion tensor imaging (DTI) studies in the related conditions of antisocial and borderline personality disorder have produced preliminary evidence of disturbed white matter connectivity in these disorders, but to date there have been no DTI studies in IED. A total of 132 male and female adults between the ages of 18 and 55 years underwent Turboprop-DTI on a 3-Tesla MRI scanner. Of these, 42 subjects had IED, 40 were normal controls, and 50 were clinical psychiatric controls with psychiatric disorders without IED. All subjects were free of alcohol, psychotropic medications, or drugs of abuse. The diffusion tensor was calculated in each voxel and maps of fractional anisotropy (FA) were generated. Tract-based spatial statistics (TBSS) were used to compare FA along the white matter skeleton among the three subject groups. IED was associated with lower FA in two clusters located in the superior longitudinal fasciculus (SLF) when compared with the psychiatric and healthy controls. Impulsive aggression and borderline personality disorder, but not psychopathy or antisocial personality disorder, was associated with lower FA in the two clusters within the SLF. In conclusion, IED was associated with lower white matter integrity in long-range connections between the frontal and temporoparietal regions.