Elsevier

NeuroImage

Volume 35, Issue 4, 1 May 2007, Pages 1538-1546
NeuroImage

Attention alters neural responses to evocative faces in behaviorally inhibited adolescents

https://doi.org/10.1016/j.neuroimage.2007.02.006Get rights and content

Abstract

Behavioral inhibition (BI) is a risk factor for anxiety disorders. While the two constructs bear behavioral similarities, previous work has not extended these parallels to the neural level. This study examined amygdala reactivity during a task previously used with clinically anxious adolescents. Adolescents were selected for enduring patterns of BI or non-inhibition (BN). We examined amygdala response to evocative emotion faces in BI (N = 10, mean 12.8 years) and BN (N = 17, mean 12.5 years) adolescents while systematically manipulating attention. Analyses focused on amygdala response during subjective ratings of internal fear (constrained attention) and passive viewing (unconstrained attention) during the presentation of emotion faces (Happy, Angry, Fearful, and Neutral). BI adolescents, relative to BN adolescents, showed exaggerated amygdala response during subjective fear ratings and deactivation during passive viewing, across all emotion faces. In addition, the BI group showed an abnormally high amygdala response to a task condition marked by novelty and uncertainty (i.e., rating fear state to a Happy face). Perturbations in amygdala function are evident in adolescents temperamentally at risk for anxiety. Attention state alters the underlying pattern of neural processing, potentially mediating the observed behavioral patterns across development. BI adolescents also show a heightened sensitivity to novelty and uncertainty, which has been linked to anxiety. These patterns of reactivity may help sustain early temperamental biases over time and contribute to the observed relation between BI and anxiety.

Introduction

Behavioral inhibition is an early-appearing temperament marked by a tendency to withdraw or show reticence in the face of novel social situations (Kagan et al., 1988). Behaviorally inhibited children are hypervigilant during situations of uncertainty or novelty and are often labeled as “shy” by both adults and their peers (Coplan et al., 1994, Fox et al., 1995). In characterizing the construct, Kagan and colleagues (Garcia Coll et al., 1984, Kagan et al., 1984) drew extensively on work describing the structure and function of the fear circuit (Amaral, 1986, Davis et al., 1997). The constellation of behaviors comprising behavioral inhibition was hypothesized to reflect increased reactivity of the amygdala.

Research has proceeded for the last two decades based on this model using behavioral (e.g., motoric reactivity in infancy) and psychophysiological (e.g., autonomic reactivity) markers theoretically linked to amygdalar functioning (Fox et al., 2005, Pérez-Edgar and Fox, 2005). The first direct observations of amygdala activity in vivo associated with behavioral inhibition emerged in the last few years (Schwartz et al., 2003). Schwartz et al. (2003) demonstrated that young adults characterized as behaviorally inhibited in the second year of life exhibited amygdala hyper-reactivity to novel faces with neutral expressions relative to familiar faces with the same neutral expression. The authors argued that the heightened amygdala activity displayed by these adults identified as behaviorally inhibited in childhood was a result of their heightened response to novelty. These data were the first to report direct links between early behavioral inhibition and amygdala activity, laying the foundation for the current study.

Interest in behavioral inhibition has grown with the publication of reports linking early inhibition to anxiety later in life (Goldsmith and Lemery, 2000, Kagan, 2001, Kagan et al., 2001, Pérez-Edgar and Fox, 2005). For example, children of parents with panic disorder have higher levels of behavioral inhibition (Rosenbaum et al., 1988), while children high in behavioral inhibition are more likely to show anxious symptomatology (Hirshfeld et al., 1992). Behavioral inhibition and anxiety are both marked by withdrawal and avoidant behavior (Pine, 1999). Behavioral inhibition and anxiety also share core psychophysiological markers, including right frontal EEG asymmetry (Fox et al., 2001), enhanced stress response in the L-HPA axis (Schmidt et al., 1997), perturbations in heart rate and vagal tone (Marshall and Stevenson-Hinde, 1998), and enhanced startle response (Schmidt and Fox, 1999). Of note, no imaging studies to date have examined behaviorally inhibited individuals using tasks previously used to differentiate clinically anxious individuals from the general population, or vice versa. As such, we do not know if the parallels between anxiety and behavioral inhibition extend to the neural level.

McClure et al. (2007) recently demonstrated alterations in amygdala function in adolescents with anxiety disorders. As predicted, anxious adolescents showed enhanced amygdala reactivity to faces with fearful expressions during a face-processing task in the fMRI environment. This excessive amygdala response was modulated by attention: the response was evident only when attention was directed towards internal feelings of fear and could not be detected in other attention conditions. Of note, when participants were asked to simply passively view fearful faces (i.e., attention is unconstrained), the anxious adolescents exhibited significant amygdala deactivation. Furthermore, anxious adolescents showed a distinct amygdala response selectively to fearful faces (with a similar trend for angry faces) that did not extend to neutral or happy faces.

The present work sought to extend the Schwartz et al. (2003) and McClure et al. (2007) findings by examining behaviorally inhibited adolescents’ responses to evocative stimuli using the identical paradigm employed by McClure et al. (2007). The cohort of behaviorally inhibited adolescents studied here had been identified in infancy and were characterized with regard to behavioral inhibition throughout preschool and childhood (Fox et al., 1995, Fox et al., 2001). This provided the opportunity to identify and examine a group of children exhibiting an enduring pattern of high levels of behavioral inhibition. This group was contrasted with a sample of non-inhibited children from the same cohort who did not display stable inhibition across development but rather typical variations in their pattern of social behavior.

The current study examined the hypothesis that adolescents characterized with behavioral inhibition would display similar neural responses to fear faces as adolescents with anxiety disorders. Based on McClure et al. (2007) we predicted (1) heightened amygdala activation in response to fearful facial expressions, when attention is focused on self-assessment of fear state, in inhibited compared to non-inhibited adolescents, and (2) amygdala deactivation in response to fearful facial expressions in passive viewing in inhibited adolescents only. In addition, based on the work of Kagan et al. (Kagan, 1997, Kagan and Snidman, 2004) and Schwartz et al. (2003) we predict that the inhibited adolescents will show heightened amygdala activity when presented with novelty or discrepancy (e.g., rating fear state to a Happy stimulus).

Section snippets

Subject classification

Forty-four adolescents participated in the current study. The adolescents were drawn from a longitudinal study of temperament and affect regulation (Fox et al., 1995, Fox et al., 2001). This longitudinal cohort included 153 children who were selected in infancy and evaluated at ages 3 months, 14 months, 24 months, 4 years, and 7 years. At each visit, measures of temperamental and psychophysiological reactivity were collected in the laboratory (Calkins et al., 1996, Fox et al., 2001, Henderson

Behavioral data

The omnibus ANOVA examining the effects of Emotion, Attention, and Temperament on the 5-point subjective rating scores revealed no significant interactions involving Temperament, Fs < 2.12, ps > 0.13 (Fig. 1). This includes the omnibus three-way interaction between Emotion, Attention, and Temperament, F(6,144) = 1.32, p = 0.27, ε = 0.60, f = 0.26.

However, there were significant main effects for Emotion and Attention, Fs > 22.89, ps < 0.001, indicating that ratings differed significantly as a function of the

Discussion

The current study is among the first to investigate the role temperament may play in affective processing and its modulation by attention at the neural level. Perturbations in affect and attention have been specifically implicated in the early emergence of anxiety disorders (Rauch et al., 2003), and an examination of these factors in a population at risk for anxiety may help further our understanding of the underlying etiology of this family of disorders. The data generated by the current study

Conclusion

Taken together, the present findings revealed a distinct pattern of amygdala responses in behaviorally inhibited adolescents to evocative stimuli as a function of attention state and task uncertainty. This pattern bears common and distinct characteristics compared to findings in anxious patients.

First, attention manipulations produce broad shifts in reactivity that do not appear to be influenced by the nature of stimulus emotion. This is in contrast to the specificity to fear evident in anxious

Acknowledgments

This work was supported by the National Institute of Mental Health (K01 MH073569-01 to KPE) and the National Institute of Child Health and Human Development (R01 HD044651-01 to NAF). We would like to thank S. Barton for assistance in participant recruitment, H. Iwamoto and S. Fromm for technical support, and the clinical staff for the psychiatric evaluations of the participants. We are deeply indebted to the families who have participated and continue to participate in this research.

References (61)

  • C.S. Monk et al.

    Adolescent immaturity in attention-related brain engagement to emotional facial expressions

    NeuroImage

    (2003)
  • K. Pérez-Edgar et al.

    Temperament and anxiety disorders

    Child Adolesc. Psychiatr. Clin. N. Am.

    (2005)
  • L. Pessoa et al.

    Fate of unattended fearful faces in the amygdala is determined by both attentional resources and cognitive modulation

    NeuroImage

    (2005)
  • P. Petrovic et al.

    A PET activation study of dynamic mechanical allodynia in patients with mononeuropathy

    Pain

    (1999)
  • D.S. Pine et al.

    Face-emotion processing in offspring at risk for panic disorder

    J. Am. Acad. Child Adolesc. Psych.

    (2005)
  • R. Roberson-Nay et al.

    Increased amygdala activity during successful memory encoding in adolescent major depressive disorder: an fMRI study

    Biol. Psychiatry

    (2006)
  • E. Zarahn et al.

    A trial-based experimental design for fMRI

    NeuroImage

    (1997)
  • D.G. Amaral

    Amygdalohippocampal and amygdalocortical projections in the primate brain

    Adv. Exp. Med. Biol.

    (1986)
  • M.G. Baxter et al.

    The amygdala and reward

    Nat. Rev., Neurosci.

    (2002)
  • M.G. Baxter et al.

    Control of response selection by reinforcer value requires interaction of amygdala and orbital prefrontal cortex

    J. Neurosci.

    (2000)
  • S.D. Calkins et al.

    Behavioral and physiological antecedents of inhibited and uninhibited behavior

    Child Dev.

    (1996)
  • R.J. Coplan et al.

    Being alone, playing alone, and acting alone: distinguishing among reticence and passive and active solitude in young children

    Child Dev.

    (1994)
  • M. Davis et al.

    The amygdala: vigilance and emotion

    Mol. Psychiatry

    (2001)
  • M. Davis et al.

    Amygdala and bed nucleus of the stria terminalis: differential roles in fear and anxiety measured with the acoustic startle reflex

    Philos. Trans. R. Soc. Lond., Ser. B Biol. Sci.

    (1997)
  • M.J. Dugas et al.

    The role of intolerance of uncertainty in etiology and maintenance

  • P. Ekman et al.

    Pictures of Facial Affect

    (1976)
  • N.A. Fox et al.

    Frontal activation asymmetry and social competence at four years of age

    Child Dev.

    (1995)
  • N.A. Fox et al.

    Continuity and discontinuity of behavioral inhibition and exuberance: psychophysiological and behavioral influences across the first four years of life

    Child Dev.

    (2001)
  • N.A. Fox et al.

    Behavioral inhibition: linking biology and behavior within a developmental framework

    Annu. Rev. Psychol.

    (2005)
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