Dynamic activation of the anterior cingulate cortex during anticipatory anxiety

Based on theoretical models, we investigated the dynamics of brain activation during anticipatory anxiety using functional magnetic resonance imaging and a combined parametric/correlational design. Subjects (16 females) anticipated the application of electrical shocks of varying intensity resulting in four different threat levels. The parametric analysis revealed an inverted U-function of activation in the ventral anterior cingulate cortex (ACC) depending on the level of threat. Furthermore, the correlation analysis showed that the association between anxiety and brain activation in the pregenual ACC was, as a tendency, positive during moderate threat but clearly negative during strong threat. Moreover, during strong threat, a positive correlation between anxiety and activation was observed in the dorsal ACC, somatosensory cortex, motor cortex, and hippocampus. These findings suggest threat dependent dynamics of brain activation in the ACC; with increased attentional avoidance during moderate threat and a switch to hypervigilant action readiness in the most anxious subjects during strong threat.

[1]  Jesper Andersson,et al.  Predictability modulates the affective and sensory-discriminative neural processing of pain , 2006, NeuroImage.

[2]  Thomas Weiss,et al.  Time course of amygdala activation during aversive conditioning depends on attention , 2007, NeuroImage.

[3]  Barry Dainton,et al.  Stream of Consciousness , 2000, Tragedy of the Commons (Poetry).

[4]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[5]  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 .

[6]  D. Hassabis,et al.  When Fear Is Near: Threat Imminence Elicits Prefrontal-Periaqueductal Gray Shifts in Humans , 2007, Science.

[7]  K. Luan Phan,et al.  Functional Neuroanatomy of Emotion: A Meta-Analysis of Emotion Activation Studies in PET and fMRI , 2002, NeuroImage.

[8]  J. Duncan,et al.  Prefrontal cortical function and anxiety: controlling attention to threat-related stimuli , 2004, Nature Neuroscience.

[9]  E. Kandel,et al.  Resolving Emotional Conflict: A Role for the Rostral Anterior Cingulate Cortex in Modulating Activity in the Amygdala , 2006, Neuron.

[10]  Richard J. Davidson,et al.  Functional neuroanatomy of aversion and its anticipation , 2006, NeuroImage.

[11]  Paul C Fletcher,et al.  Does the brain have a baseline? Why we should be resisting a rest. , 2007, NeuroImage.

[12]  A. Craig How do you feel? Interoception: the sense of the physiological condition of the body , 2002, Nature Reviews Neuroscience.

[13]  David Silbersweig,et al.  Fear-related activity in subgenual anterior cingulate differs between men and women , 2005, Neuroreport.

[14]  Thomas Weiss,et al.  Sex differences in brain activation to anticipated and experienced pain in the medial prefrontal cortex , 2009, Human brain mapping.

[15]  E. Kandel,et al.  Resolving Emotional Conflict: A Role for the Rostral Anterior Cingulate Cortex in Modulating Activit , 2006 .

[16]  K. Mogg,et al.  A cognitive-motivational analysis of anxiety. , 1998, Behaviour research and therapy.

[17]  Jonathan D. Cohen,et al.  Improved Assessment of Significant Activation in Functional Magnetic Resonance Imaging (fMRI): Use of a Cluster‐Size Threshold , 1995, Magnetic resonance in medicine.

[18]  M. Raichle,et al.  Emotion-induced changes in human medial prefrontal cortex: II. During anticipatory anxiety. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Jeffrey R. Binder,et al.  Interrupting the “stream of consciousness”: An fMRI investigation , 2006, NeuroImage.

[20]  R. Lane,et al.  Neural Correlates of Levels of Emotional Awareness: Evidence of an Interaction between Emotion and Attention in the Anterior Cingulate Cortex , 1998, Journal of Cognitive Neuroscience.

[21]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

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

[23]  B. Bromm,et al.  The intracutaneous stimulus: a new pain model for algesimetric studies. , 1984, Methods and findings in experimental and clinical pharmacology.

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

[25]  Ravi S. Menon,et al.  Dissociating pain from its anticipation in the human brain. , 1999, Science.

[26]  H. Critchley The human cortex responds to an interoceptive challenge. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[27]  P. Matthews,et al.  Exacerbation of Pain by Anxiety Is Associated with Activity in a Hippocampal Network , 2001, The Journal of Neuroscience.

[28]  Gregor Hasler,et al.  Cerebral Blood Flow in Immediate and Sustained Anxiety , 2007, The Journal of Neuroscience.

[29]  Darin D Dougherty,et al.  Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. , 2004, Archives of general psychiatry.

[30]  M. Paulus,et al.  An Insular View of Anxiety , 2006, Biological Psychiatry.

[31]  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.

[32]  J. Gray,et al.  Précis of The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system , 1982, Behavioral and Brain Sciences.

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

[34]  L. Becerra,et al.  Neural circuitry underlying pain modulation: expectation, hypnosis, placebo , 2003, Trends in Cognitive Sciences.

[35]  Bruce Fischl,et al.  A Role for the Human Dorsal Anterior Cingulate Cortex in Fear Expression , 2007, Biological Psychiatry.

[36]  R. Dolan,et al.  A Functional Anatomy of Anticipatory Anxiety , 1999, NeuroImage.