Exposure to family violence affects a significant minority of children: estimates of physical abuse range from 4 to 16%, while intimate partner violence affects between 8 and 25% of children []. These maltreatment experiences represent a form of environmental stress that significantly increases risk of later psychopathology, including anxiety []. To date, no functional magnetic resonance imaging (fMRI) studies have probed the neural correlates of emotional processing in children exposed to family violence. Previous psychological and electrophysiological studies indicate a selective hypervigilance to angry cues in physically abused children, which is in turn associated with elevated levels of anxiety []. Functional magnetic resonance imaging (fMRI) research has demonstrated increased reactivity of the anterior insula (AI) and amygdala to angry faces in individuals with anxiety disorder [], and in psychiatrically healthy soldiers exposed to combat [], making these regions plausible neural candidates for adaptation to threat. We demonstrated that children exposed to family violence (with normative levels of anxiety) show increased AI and amygdala reactivity in response to angry but not sad faces. While such enhanced reactivity to a biologically salient threat cue may represent an adaptive response to sustained environmental danger, it may also constitute a latent neurobiological risk factor increasing vulnerability to psychopathology.

Main Text

Figure 1 Example stimuli and functional magnetic resonance imaging activation. Show full caption (A) Participants viewed blocks of angry, neutral and sad faces in a pseudorandom order while indicating the gender of the target. (B) Statistical parametric map (SPM) showing increased right amygdala activation in children exposed to family violence for the contrast angry > neutral (36, 2, -23, z = 3.31, p =.0014, Family-Wise Error (FWE) corrected). (C) Increased bilateral AI activation in children exposed to family violence for the contrast angry > neutral (left AI: –42, 8, -2, z = 3.52, p = 0.033, FWE corrected; right AI: 33, 14, 4, z = 3.75, p = 0.014, FWE corrected). All coordinates reference the coordinate system of the Montreal Neurological Institute. SPM thresholded at p < 0.005 (uncorrected) for visualization purposes. (D) Scatter plot depicting the correlation between the contrast estimates (angry > neutral) from the left anterior insula (y axis) and degree of family violence exposure (x axis) after accounting for variance explained by age and gender. Using fMRI we investigated brain responses to threatening (angry) and non-threatening (sad) facial expressions relative to neutral faces (see Figure 1 A and Supplemental Experimental Procedures in the Supplemental Information for paradigm description) in children who had been exposed to documented violence at home (n = 20). These children presented with normal levels of anxiety and depression. Brain responses were compared to that of a closely matched comparison group (n = 23; see Supplemental Experimental Procedures and Supplemental Table S1 for additional participant details). The emotional content of the facial stimuli was incidental to our task, which required children to decide if a series of faces were male or female (see Supplemental Results and Table S2 for reaction time and accuracy data for the two groups). Compared to our comparison group, the family violence group exhibited greater activation in the right amygdala ( Figure 1 B) and in the AI bilaterally ( Figure 1 C) when angry faces, but not sad faces, were contrasted with neutral faces. In an exploratory analysis, we also examined a possible dose-response relationship between these neural activations and violence exposure within the family violence group. The degree of activation to angry faces in the left AI was positivelycorrelated with the severity of violence exposure (r(20) = 0.54, p = 0.007, one-tailed; Figure 1 D).

6 Pichon S.

de Gelder B.

Grèzes J. Threat prompts defensive brain responses independently of attentional control. 7 Wiech K.

Lin C.S.

Brodersen K.H.

Bingel U.

Ploner M.

Tracey I. Anterior insula integrates information about salience into perceptual decisions about pain. 8 Singer T.

Critchley H.D.

Preuschoff K. A common role of insula in feelings, empathy and uncertainty. 7 Wiech K.

Lin C.S.

Brodersen K.H.

Bingel U.

Ploner M.

Tracey I. Anterior insula integrates information about salience into perceptual decisions about pain. 7 Wiech K.

Lin C.S.

Brodersen K.H.

Bingel U.

Ploner M.

Tracey I. Anterior insula integrates information about salience into perceptual decisions about pain. 6 Pichon S.

de Gelder B.

Grèzes J. Threat prompts defensive brain responses independently of attentional control. 9 Santos A.

Mier D.

Kirsch P.

Meyer-Lindenberg A. Evidence for a general face salience signal in human amygdala. Neuroimaging studies of healthy adults suggest that the amygdala and the AI are part of a larger salience network that detects threat [] and anticipates pain []. The AI shares dense connections with a number of cortical and subcortical regions (including the amygdala) and is therefore well placed to integrate emotional, sensory and bodily information to guide social processing and affective decision-making []. This region has been implicated specifically in the anticipation of a physical stimulus, generating a predictive signal as to how the body will feel. For example, greater pre-stimulus activation in the AI bilaterally has been shown to be predictive of the perceived painfulness of that stimulus []. This is consistent with the proposal that the insula supports the interaction between perceived threat signals and bodily states of arousal leading to emotional experiences []. The role of the amygdala in detecting threat is widely recognized [], with recent evidence suggesting that, in the context of face processing, it predominantly signals salience independent of level of threat or degree of emotionality [].

10 Tottenham N.

Hare T.A.

Millner A.

Gilhooly T.

Zevin J.D.

Casey B.J. Elevated amygdala response to faces following early deprivation. 5 Van Wingen G.A.

Geuze E.

Vermetten E.

Fernández G. Perceived threat predicts the neural sequelae of combat stress. 4 Etkin A.

Wager T.D. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. 5 Van Wingen G.A.

Geuze E.

Vermetten E.

Fernández G. Perceived threat predicts the neural sequelae of combat stress. 4 Etkin A.

Wager T.D. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Recently it has been shown that children exposed to early stress in the form of institutionalisation and removal from their families show heightened activation of the amygdala when viewing fearful faces; this suggests that poor caregiving may alter functional development of limbic structures []. In adults, studies of soldiers exposed to combat have been used to study prolonged experience of stress, and specifically exposure to environmental threat. In a recent longitudinal study [], both the AI and amgygdala demonstrated functional adaptation in soldiers exposed to a combat zone: combat stress increased AI and amygdala reactivity to angry and fearful faces, even in the absence of self-reported changes in post-traumatic stress symptoms or other measures of psychopathology. This suggests that sustained exposure to environmental danger and potential physical harm recalibrates the neural responsiveness of these regions, which are densely inter-connected []. Functionally, this may augment vigilance to threat, but it is thought that heightened neural reactivity in the AI and amygdala is not adaptive in safe environments and may serve as a latent risk factor for subsequent anxiety disorders []. A meta-analysis of functional imaging studies found increased reactivity of both the AI and amygdala to threat to be reliably associated with several anxiety disorders, including post-traumatic stress disorder []. While disorder-specific activations in other brain areas were also reported, atypical activations of these two structures represented a neural signature associated with anxiety-disordered processing.

3 Pollak S.D. Mechanisms linking early experience and the emergence of emotions: Illustrations from the study of maltreated children. Clinically, these findings indicate that even sub-threshold trauma symptoms may conceal significantly heightened neural responsiveness to threat. We suggest that such threat hypervigilance may compromise a child's development in at least three ways. First, it could limit attentional resources for mastering age-appropriate skills in social and cognitive domains []. Second, it may serve to increase future vulnerability to later stressors, increasing risk of anxiety. Finally, it may predispose to reactive aggression. Our findings are consistent with a pattern of amplified emotional reactivity to anger that may underpin inappropriate behavioural responses to such cues from peers and adults.