Vigilance for Threat Interacts with Amygdala Responses to Subliminal Threat Cues in Specific Phobia

BACKGROUND The amygdala has been strongly implicated in the processing of threat-relevant information in specific phobia. However, there is an ongoing debate as to whether the amygdala may also be engaged outside of conscious stimulus awareness. Furthermore, considering that sustained vigilance for threat constitutes a crucial characteristic of specific phobias, we hypothesized a possible role of this symptom in modulating amygdala sensitivity to disorder-relevant cues. Using event-related functional magnetic resonance imaging, we examined responses of the amygdala to subliminal and supraliminal phobogenic stimuli in spider-phobic subjects and whether these responses might be specifically associated with disorder-related hypervigilance. METHODS Eighteen female spider-phobic subjects and 18 healthy female control subjects were exposed to pictures of spiders and phobia-irrelevant objects, presented briefly during two backward-masking conditions used to manipulate stimulus awareness. Brain activation data were analyzed as a function of subjects' perceptual performance on each single trial and were tested for correlations with different components of the phobic symptomatology, such as vigilance, as assessed by self-report scales. RESULTS Compared with control subjects, phobic participants showed stronger responses of both amygdalae to consciously perceived spiders versus nonspider targets, whereas during unconscious stimulus processing, enhanced activation was only apparent in the right amygdala. Moreover, the intensity of disorder-related vigilance was positively correlated with right amygdala activation specifically during the subliminal condition. CONCLUSIONS These findings provide evidence for unconscious threat processing in specific phobia, with the magnitude of amygdala responses specifically potentiated by sustained hypervigilance for threat. Aberrations in this vigilance system may be critically involved in anxiety disorders.

[1]  L. Pessoa To what extent are emotional visual stimuli processed without attention and awareness? , 2005, Current Opinion in Neurobiology.

[2]  M. Eysenck Anxiety: The Cognitive Perspective , 1992 .

[3]  Richard J. Davidson,et al.  Fear Is Fast in Phobic Individuals: Amygdala Activation in Response to Fear-Relevant Stimuli , 2006, Biological Psychiatry.

[4]  Edward T. Bullmore,et al.  Differential neural responses to overt and covert presentations of facial expressions of fear and disgust , 2000, NeuroImage.

[5]  P. Holland,et al.  Amygdala circuitry in attentional and representational processes , 1999, Trends in Cognitive Sciences.

[6]  D. Amaral,et al.  Topographic organization of projections from the amygdala to the visual cortex in the macaque monkey , 2003, Neuroscience.

[7]  A. Ohman,et al.  Fear and the amygdala: manipulation of awareness generates differential cerebral responses to phobic and fear-relevant (but nonfeared) stimuli. , 2004, Emotion.

[8]  W. Miltner,et al.  Behavioral and Brain Functions , 2008 .

[9]  Thomas Straube,et al.  Brain activation to phobia-related pictures in spider phobic humans: an event-related functional magnetic resonance imaging study , 2003, Neuroscience Letters.

[10]  J. Cisler,et al.  Examining information processing biases in spider phobia using the rapid serial visual presentation paradigm. , 2007, Journal of anxiety disorders.

[11]  Rainer Goebel,et al.  Analysis of functional image analysis contest (FIAC) data with brainvoyager QX: From single‐subject to cortically aligned group general linear model analysis and self‐organizing group independent component analysis , 2006, Human brain mapping.

[12]  Neil A. Macmillan,et al.  Detection Theory: A User's Guide , 1991 .

[13]  Peter J. Lang,et al.  Parallel amygdala and inferotemporal activation reflect emotional intensity and fear relevance , 2005, NeuroImage.

[14]  J. Changeux,et al.  Opinion TRENDS in Cognitive Sciences Vol.10 No.5 May 2006 Conscious, preconscious, and subliminal processing: a testable taxonomy , 2022 .

[15]  Paul J. Whalen,et al.  Amygdaloid contributions to conditioned arousal and sensory information processing. , 1992 .

[16]  J. Wissmann,et al.  Reliabilität und Validität dreier Instrumente zur Messung von Angst vor Spinnen , 2002 .

[17]  W. Miltner,et al.  The volatility of the amygdala response to masked fearful eyes , 2010, Human brain mapping.

[18]  C. Pull,et al.  Recent trends in the study of specific phobias , 2008, Current opinion in psychiatry.

[19]  Thomas Straube,et al.  Neural Mechanisms of Automatic and Direct Processing of Phobogenic Stimuli in Specific Phobia , 2006, Biological Psychiatry.

[20]  R. Dolan,et al.  Conscious and unconscious emotional learning in the human amygdala , 1998, Nature.

[21]  John P. Aggleton,et al.  The amygdala: Neurobiological aspects of emotion, memory, and mental dysfunction. , 1992 .

[22]  D. Amaral,et al.  Synaptic organization of projections from the amygdala to visual cortical areas TE and V1 in the macaque monkey , 2005, The Journal of comparative neurology.

[23]  Michael Davis,et al.  The amygdala: vigilance and emotion , 2001, Molecular Psychiatry.

[24]  J L Lancaster,et al.  Automated Talairach Atlas labels for functional brain mapping , 2000, Human brain mapping.

[25]  A. Ohman,et al.  Emotion drives attention: detecting the snake in the grass. , 2001, Journal of experimental psychology. General.

[26]  S. Mineka,et al.  Fears, phobias, and preparedness: toward an evolved module of fear and fear learning. , 2001, Psychological review.

[27]  Luiz Pessoa,et al.  Target visibility and visual awareness modulate amygdala responses to fearful faces. , 2006, Cerebral cortex.

[28]  P. Whalen Fear, Vigilance, and Ambiguity , 1998 .

[29]  Leslie G. Ungerleider,et al.  Visual awareness and the detection of fearful faces. , 2005, Emotion.

[30]  P. Lang,et al.  Psychometric description of some specific-fear questionnaires. , 1974 .

[31]  Thomas Straube,et al.  Waiting for spiders: Brain activation during anticipatory anxiety in spider phobics , 2007, NeuroImage.

[32]  Evian Gordon,et al.  A Direct Brainstem–amygdala–cortical Dalarmt System for Subliminal Signals of Fear , 2004 .

[33]  R Turner,et al.  Optimized EPI for fMRI studies of the orbitofrontal cortex , 2003, NeuroImage.

[34]  Karl J. Friston,et al.  Psychophysiological and Modulatory Interactions in Neuroimaging , 1997, NeuroImage.

[35]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[36]  F. Watts,et al.  Questionnaire dimensions of spider phobia. , 1984, Behaviour research and therapy.

[37]  Thomas Straube,et al.  Effect of task conditions on brain responses to threatening faces in social phobics: An event-related functional magnetic resonance imaging study , 2004, Biological Psychiatry.

[38]  M. Lotze,et al.  Brain activation and defensive response mobilization during sustained exposure to phobia-related and other affective pictures in spider phobia. , 2008, Psychophysiology.

[39]  Neil A. Macmillan,et al.  Detection theory: A user's guide, 2nd ed. , 2005 .

[40]  M. Torrens Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[41]  Joseph E LeDoux The emotional brain , 1996 .

[42]  R. Dolan,et al.  A subcortical pathway to the right amygdala mediating "unseen" fear. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Karl J. Friston,et al.  Modeling regional and psychophysiologic interactions in fMRI: the importance of hemodynamic deconvolution , 2003, NeuroImage.

[44]  D. Barlow Unraveling the mysteries of anxiety and its disorders from the perspective of emotion theory. , 2000 .

[45]  J B Poline,et al.  Cerebral mechanisms of word masking and unconscious repetition priming , 2001, Nature Neuroscience.

[46]  R. Kessler,et al.  Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey. , 1996, Archives of general psychiatry.