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

doi:10.1016/j.biopsych.2006.08.024

Biological Psychiatry

Volume 62, Issue 2, 15 July 2007, Pages 168-178

https://doi.org/10.1016/j.biopsych.2006.08.024 Get rights and content

Background

Converging evidence from animal and human lesion studies implicates the amygdala and orbitofrontal cortex (OFC) in emotional regulation and aggressive behavior. However, it remains unknown if functional deficits exist in these specific brain regions in clinical populations in which the cardinal symptom is impulsive aggression. We have previously shown that subjects diagnosed with intermittent explosive disorder (IED), a psychiatric disorder characterized by reactive aggressive behavior, perform poorly on facial emotion recognition tasks. In this study we employed a social-emotional probe of amygdala-OFC function in individuals with impulsive aggression.

Methods

Ten unmedicated subjects with IED and 10 healthy, matched comparison subjects (HC) underwent functional magnetic resonance imaging while viewing blocks of emotionally salient faces. We compared amygdala and OFC reactivity to faces between IED and HC subjects, and examined the relationship between the extent of activation in these regions and extent of prior history of aggressive behavior.

Results

Relative to controls, individuals with IED exhibited exaggerated amygdala reactivity and diminished OFC activation to faces expressing anger. Extent of amygdala and OFC activation to angry faces were differentially related to prior aggressive behavior across subjects. Unlike controls, aggressive subjects failed to demonstrate amygdala-OFC coupling during responses to angry faces.

Conclusions

These findings provide evidence of amygdala-OFC dysfunction in response to an ecologically-valid social threat signal (processing angry faces) in individuals with a history of impulsive aggressive behavior, and further substantiate a link between a dysfunctional cortico-limbic network and aggression.

Section snippets

Participants

Ten subjects with IED-IR (Coccaro 2003b) and 10 healthy control (HC) subjects participated in this study. The diagnosis of IED-IR was based on Integrated Research Criteria for IED as first described by Coccaro (Coccaro 2003b); IED-IR integrates DSM-IV criteria for IED (American Psychiatric Association 2000) with Research Criteria for IED (Coccaro et al. 1998). Other Axis I and Axis II psychiatric diagnoses were made according to DSM-IV criteria. Final diagnoses were assigned through a best

Behavioral Results

For the on-line task, there were no group differences (p > .2) in gender-identification accuracy, with both groups achieving > 99% correct responses. Analysis of post-scan emotion recognition accuracy revealed that subjects had high accuracy rates across emotions (avg. percent correct = 83 ± 7%). There was a significant main effect of emotion on recognition accuracy (F = 6.76, p < .0001); however, there were no significant group differences in accuracy of recognition on any specific emotion

Discussion

To our knowledge, this is the first fMRI study to examine brain activation, specifically amygdala-OFC function, during emotional information processing among IED patients with an extensive history of impulsive, reactive aggression. The study probed the neuroanatomy of impulsive aggression in a clinical population to elaborate on prior findings from human lesion and animal studies. We demonstrate a putative link between amygdala-OFC dysfunction and impulsive aggression in IED on three levels of

References (95)

R.E. Adamec
Partial kindling of the ventral hippocampus: identification of changes in limbic physiology which accompany changes in feline aggression and defense
Physiol Behav
(1991)
R. Adolphs
Neural systems for recognizing emotion
Curr Opin Neurobiol
(2002)
D.G. Amaral et al.
The amygdala: is it an essential component of the neural network for social cognition?
Neuropsychologia
(2003)
E.F. Coccaro et al.
Assessment of life history of aggression: development and psychometric characteristics
Psychiatry Res
(1997)
E.F. Coccaro et al.
Intermittent explosive disorder-revised: development, reliability, and validity of research criteria
Compr Psychiatry
(1998)
N.H. Donegan et al.
Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation
Biol Psychiatry
(2003)
D.D. Dougherty et al.
Anger in healthy men: a PET study using script-driven imagery
Biol Psychiatry
(1999)
D.A. Fitzgerald et al.
Beyond threat: Amygdala reactivity across multiple expressions of facial affect
Neuroimage
(2006)
K.J. Friston et al.
Psychophysiological and modulatory interactions in neuroimaging
Neuroimage
(1997)
C.R. Genovese et al.
Thresholding of statistical maps in functional neuroimaging using the false discovery rate
Neuroimage
(2002)

H.T. Ghashghaei et al.

Pathways for emotion: interactions of prefrontal and anterior temporal pathways in the amygdala of the rhesus monkey

Neuroscience

(2002)

S.C. Herpertz et al.

Evidence of abnormal amygdala functioning in borderline personality disorder: a functional MRI study

Biol Psychiatry

(2001)

F.D. Juengling et al.

Positron emission tomography in female patients with borderline personality disorder

J Psychiatr Res

(2003)

K.A. Kiehl et al.

Limbic abnormalities in affective processing by criminal psychopaths as revealed by functional magnetic resonance imaging

Biol Psychiatry

(2001)

M.L. Kringelbach et al.

The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology

Prog Neurobiol

(2004)

M.S. McCloskey et al.

Intermittent explosive disorder-integrated research diagnostic criteria: convergent and discriminant validity

J Psychiatr Res

(2006)

J.L. Muller et al.

Abnormalities in emotion processing within cortical and subcortical regions in criminal psychopaths: evidence from a functional magnetic resonance imaging study using pictures with emotional content

Biol Psychiatry

(2003)

M. Nomura et al.

Functional association of the amygdala and ventral prefrontal cortex during cognitive evaluation of facial expressions primed by masked angry faces: an event-related fMRI study

Neuroimage

(2004)

K.N. Ochsner et al.

The cognitive control of emotion

Trends Cogn Sci

(2005)

K.L. Phan et al.

Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI

Neuroimage

(2002)

A. Raine et al.

Brain abnormalities in murderers indicated by positron emission tomography

Biol Psychiatry

(1997)

A. Raine et al.

Selective reductions in prefrontal glucose metabolism in murderers

Biol Psychiatry

(1994)

M.P. Saddoris et al.

Rapid associative encoding in basolateral amygdala depends on connections with orbitofrontal cortex

Neuron

(2005)

C.G. Schmahl et al.

A positron emission tomography study of memories of childhood abuse in borderline personality disorder

Biol Psychiatry

(2004)

Y.I. Sheline et al.

Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study

Biol Psychiatry

(2001)

L.J. Siever et al.

d,l-fenfluramine response in impulsive personality disorder assessed with [18F]fluorodeoxyglucose positron emission tomography

Neuropsychopharmacology

(1999)

P.H. Soloff et al.

Impulsivity and prefrontal hypometabolism in borderline personality disorder

Psychiatry Res

(2003)

P.H. Soloff et al.

A fenfluramine-activated FDG-PET study of borderline personality disorder

Biol Psychiatry

(2000)

L.H. Somerville et al.

Human amygdala responses during presentation of happy and neutral faces: correlations with state anxiety

Biol Psychiatry

(2004)

P. Sterzer et al.

Abnormal neural responses to emotional visual stimuli in adolescents with conduct disorder

Biol Psychiatry

(2005)

M.M. Strauss et al.

fMRI of sensitization to angry faces

Neuroimage

(2005)

L. Tebartz van Elst et al.

Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study

Biol Psychiatry

(2003)

N. Tzourio-Mazoyer et al.

Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain

Neuroimage

(2002)

R.B. Adams et al.

Effects of gaze on amygdala sensitivity to anger and fear faces

Science

(2003)

R. Adolphs et al.

Impaired recognition of social emotions following amygdala damage

J Cogn Neurosci

(2002)

R. Adolphs et al.

A mechanism for impaired fear recognition after amygdala damage

Nature

(2005)

D.G. Amaral et al.

Amygdalo-cortical projections in the monkey (Macaca fascicularis)

J Comp Neurol

(1984)

Diagnostic and statistical manual of mental disorders: DSM-IV-TR

(2000)

S.W. Anderson et al.

Impairment of social and moral behavior related to early damage in human prefrontal cortex

Nat Neurosci

(1999)

A.T. Beck et al.

An inventory for measuring depression

Arch Gen Psychiatry

(1961)

J.S. Beer et al.

The regulatory function of self-conscious emotion: insights from patients with orbitofrontal damage

J Pers Soc Psychol

(2003)

M. Best et al.

Evidence for a dysfunctional prefrontal circuit in patients with an impulsive aggressive disorder

Proc Natl Acad Sci USA

(2002)

N. Birbaumer et al.

Deficient fear conditioning in psychopathy: a functional magnetic resonance imaging study

Arch Gen Psychiatry

(2005)

R.J. Blair

Neurobiological basis of psychopathy

Br J Psychiatry

(2003)

R.J. Blair et al.

Dissociable neural responses to facial expressions of sadness and anger

Brain

(1999)

R.J. Blair et al.

The development of psychopathy

J Child Psychol Psychiatry

(2006)

A.H. Buss et al.

The aggression questionnaire

J Pers Soc Psychol

(1992)

Cited by (478)

The role of external factors in affect-sharing and their neural bases
2024, Neuroscience and Biobehavioral Reviews
Affect-sharing, the ability to vicariously feel another person's emotions, is the primary component of empathy that is typically thought to rely on the observer's capacity to feel the emotions of others. However, external signals, such as the target's physical characteristics, have been demonstrated to influence affect-sharing in the neuroscientific literature that speaks to the underappreciated role of external factors in eliciting affect-sharing. We consider factors that influence affect-sharing, including physical cues, emotional cues, situational factors, and observer-target relationships, as well as the neural circuits involved in these processes. Our review reveals that, while neural network activation is primarily responsible for processing affect-sharing, external factors also co-activate a top-down cognitive processing network to modulate the conscious process of affect-sharing. From this knowledge, an integrative framework of external factor interactions with affect-sharing are explained in detail. Finally, we identify critical areas for future research in social and affective neuroscience, including research gaps and incorporation of ecologically valid paradigms.
A systematic review with meta-analysis of cognitive bias modification interventions for anger and aggression
2023, Behaviour Research and Therapy
Aggression and anger are associated with interpretation and attention biases. Such biases have become treatment targets for anger and aggressive behavior in cognitive bias modification (CBM) interventions. Several studies have evaluated the efficacy of CBM for the treatment of anger and aggressive behavior, with inconsistent results. The present study meta-analytically analyzed 29 randomized controlled trial studies (N = 2334) published in EBSCOhost and PubMed between March 2013 and March 2023 assessing the efficacy of CBM for anger and/or aggression. Included studies delivered CBMs that addressed either attention biases, interpretation biases, or both. Risk of publication bias and potential moderating effects of several participant-, treatment- and study-related factors were assessed. CBM significantly outperformed control conditions in the treatment of aggression (Hedge's G = −0.23, 95% CI [-0.35, −0.11], p < .001) and anger (Hedge's G = −0.18, 95% CI [-0.28, −0.07], p = .001) independent of treatment dose, participant demographic characteristics, and study quality, though overall effects were small. Follow-up analyses demonstrated that only CBMs targeting interpretation bias were efficacious for aggression outcomes, but not when baseline aggression was accounted for. Findings suggest that CBM demonstrates efficacy for the treatment aggressive behavior and to a lesser extent, anger.
PTSD and crime propensity: Stress systems, brain structures, and the nature of the relationship
2023, Heliyon
Post-traumatic stress disorder (PTSD) is the most commonly found disorder among the prison population; however, research has been slow to study it as a potential cause of crime. This review examines the neurophysiological changes in the organism associated with PTSD and connects them to crime and antisocial behaviour. Patients with PTSD suffer from a hyperactive sympathetic nervous system (SNS), an overactive amygdala that results in a hypoactive hypothalamic‒pituitary‒adrenal (HPA) axis, and a reduced hippocampal volume. All these features have been separately associated with aggressivity and antisocial behaviour; however, no consensus has been reached. Moreover, very little research has addressed the need to study the interaction between several stress-response systems. As a result, although there is some indication that patients with PTSD are probabilistically more likely to commit acts of crime, no conclusive results on the influence of PTSD on crime propensity can yet be drawn. Future research should address the interaction between the stress-response systems to understand the nature of antisocial behaviour and violence as well as to study any possible links between PTSD prevalence and possible unrest in prisons.
Salivary cortisol awakening levels are reduced in human subjects with intermittent explosive disorder compared with controls
2023, Psychoneuroendocrinology
The role of the hypothalamic-pituitary-adrenal (HPA) axis in human aggressive behavior is poorly characterized, though some studies report that, unlike depression, circulating or salivary levels of cortisol are low compared with controls.
In this study, we collected three salivary cortisol levels (two in the morning and one in the evening) on three separate days in 78 adult study participants with (n = 28) and without (n = 52) prominent histories of impulsive aggressive behavior. Plasma C-Reactive Protein (CRP) and Interleukin-6 (IL-6) were also collected in most study participants. Aggressive study participants meet DSM-5 criteria for Intermittent Explosive Disorder (IED) while non-aggressive participants either had a history of a psychiatric disorder or no such history (Controls).
Morning, but not evening, salivary cortisol levels were significantly lower in IED (p < 0.05), compared with control, study participants. In addition, salivary cortisol levels correlated with measures of trait anger (partial r = −0.26, p < 0.05) and aggression (partial r = −0.25, p < 0.05) but not with measures of impulsivity, psychopathy, depression, history of childhood maltreatment, or other tested variables that often differ in individuals with IED. Finally, plasma CRP levels correlated inversely with morning salivary cortisol levels (partial r = −0.28, p < 0.05); plasma IL-6 levels showed a similar, though not statistically significant (r_p = −0.20, p = 0.12) relationship with morning salivary cortisol levels.
The cortisol awakening response appears to be lower in individuals with IED compared with controls. In all study participants, morning salivary cortisol levels correlated inversely with trait anger, trait aggression, and plasma CRP, a marker of systemic inflammation. This suggests the present of a complex interaction between chronic-low level inflammation, the HPA axis, and IED that warrants further investigation.
Lower cerebello-cortical functional connectivity in veterans with reactive aggression symptoms: A pilot study
2023, Journal of Psychiatric Research
A significant number of veterans experience irritability and aggression symptoms as a result of being exposed to extremely stressful and life-threatening situations. In addition to the well-established involvement of the brain's cortico-subcortical circuit in aggression-related behaviours, a role of the deep cerebellar nuclei (DCN) in reactive aggression has been suggested. In the present study, seed-based resting-state functional connectivity between the DCN and cortico-subcortical areas was explored in veterans with and without reactive aggression symptoms. Nineteen male veterans with reactive aggression symptoms and twenty-two control veterans without reactive aggression symptoms underwent 3T resting-state functional MRI scans. Region-of-interest (ROI) analyses that included the amygdala, hypothalamus and periaqueductal grey as ROIs did not yield significant group-related differences in resting-state functional connectivity with the DCN. However, exploratory whole-brain analysis showed that veterans with reactive aggression symptoms exhibited lower functional connectivity between the DCN and the orbitofrontal cortex compared to control veterans. Our findings provide preliminary evidence for the possible involvement of a cerebello-prefrontal pathway in reactive aggression in male veterans.
Amygdala connectivity and aggression
2023, Handbook of Clinical Neurology
Neurobiological models propose that reactive aggression is predicated on impairments in amygdala–prefrontal connectivity that subserves moral decision-making and emotion regulation. The amygdala is a key component within this neural network that modulates reactive aggression. We provide a review of amygdala dysfunctional brain networks leading to reactive aggressive behavior. We elaborate on key concepts, focusing on moral decision-making and emotion regulation in a developmental context, and brain network connectivity factors relating to amygdala (dys)function—factors which we suggest predispose to reactive aggression. We additionally discuss insights into the latest treatment interventions, providing the utilization of the scientific findings for practice.

View all citing articles on Scopus

View full text

Original ArticleAmygdala and Orbitofrontal Reactivity to Social Threat in Individuals with Impulsive Aggression

Background

Methods

Results

Conclusions

Section snippets

Participants

Behavioral Results

Discussion

Physiol Behav

Curr Opin Neurobiol

Neuropsychologia

Psychiatry Res

Compr Psychiatry

Biol Psychiatry

Biol Psychiatry

Neuroimage

Neuroimage

Neuroimage

Neuroscience

Biol Psychiatry

J Psychiatr Res

Biol Psychiatry

Prog Neurobiol

J Psychiatr Res

Biol Psychiatry

Neuroimage

Trends Cogn Sci

Neuroimage

Biol Psychiatry

Biol Psychiatry

Neuron

Biol Psychiatry

Biol Psychiatry

Neuropsychopharmacology

Psychiatry Res

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Neuroimage

Biol Psychiatry

Neuroimage

Effects of gaze on amygdala sensitivity to anger and fear faces

Science

Impaired recognition of social emotions following amygdala damage

J Cogn Neurosci

A mechanism for impaired fear recognition after amygdala damage

Nature

Amygdalo-cortical projections in the monkey (Macaca fascicularis)

J Comp Neurol

Diagnostic and statistical manual of mental disorders: DSM-IV-TR

Impairment of social and moral behavior related to early damage in human prefrontal cortex

Nat Neurosci

An inventory for measuring depression

Arch Gen Psychiatry

The regulatory function of self-conscious emotion: insights from patients with orbitofrontal damage

J Pers Soc Psychol

Evidence for a dysfunctional prefrontal circuit in patients with an impulsive aggressive disorder

Proc Natl Acad Sci USA

Deficient fear conditioning in psychopathy: a functional magnetic resonance imaging study

Arch Gen Psychiatry

Neurobiological basis of psychopathy

Br J Psychiatry

Dissociable neural responses to facial expressions of sadness and anger

Brain

The development of psychopathy

J Child Psychol Psychiatry

The aggression questionnaire

J Pers Soc Psychol

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