When Fear Is Near: Threat Imminence Elicits Prefrontal-Periaqueductal Gray Shifts in Humans

Humans, like other animals, alter their behavior depending on whether a threat is close or distant. We investigated spatial imminence of threat by developing an active avoidance paradigm in which volunteers were pursued through a maze by a virtual predator endowed with an ability to chase, capture, and inflict pain. Using functional magnetic resonance imaging, we found that as the virtual predator grew closer, brain activity shifted from the ventromedial prefrontal cortex to the periaqueductal gray. This shift showed maximal expression when a high degree of pain was anticipated. Moreover, imminence-driven periaqueductal gray activity correlated with increased subjective degree of dread and decreased confidence of escape. Our findings cast light on the neural dynamics of threat anticipation and have implications for the neurobiology of human anxiety-related disorders.

[1]  F. Young Biochemistry , 1955, The Indian Medical Gazette.

[2]  W P Wilson,et al.  Sensations evoked by stimulation in the midbrain of man. , 1969, Journal of neurosurgery.

[3]  T. Jessell PAIN , 1982, The Lancet.

[4]  P T Fox,et al.  Neuroanatomical correlates of a lactate-induced anxiety attack. , 1989, Archives of general psychiatry.

[5]  S. Eykyn Microbiology , 1950, The Lancet.

[6]  J. Deakin,et al.  5-HT and mechanisms of defence , 1991, Journal of psychopharmacology.

[7]  M. Fanselow Neural organization of the defensive behavior system responsible for fear , 1994, Psychonomic bulletin & review.

[8]  Arthur W. Toga,et al.  A Probabilistic Atlas of the Human Brain: Theory and Rationale for Its Development The International Consortium for Brain Mapping (ICBM) , 1995, NeuroImage.

[9]  Peter Norvig,et al.  Artificial Intelligence: A Modern Approach , 1995 .

[10]  B. Vogt,et al.  Contributions of anterior cingulate cortex to behaviour. , 1995, Brain : a journal of neurology.

[11]  Streichenwein Sm,et al.  Am J Psychiatry , 1996 .

[12]  Michelle G. Craske,et al.  Anxiety Disorders: Psychological Approaches To Theory And Treatment , 1998 .

[13]  J. Tanji,et al.  Role for cingulate motor area cells in voluntary movement selection based on reward. , 1998, Science.

[14]  S. Stone-Elander,et al.  Anticipatory coping of pain expressed in the human anterior cingulate cortex: a positron emission tomography study , 1999, Neuroscience Letters.

[15]  J M Gorman,et al.  Neuroanatomical hypothesis of panic disorder, revised. , 2000, The American journal of psychiatry.

[16]  R Bandler,et al.  Orbitomedial prefrontal cortical projections to distinct longitudinal columns of the periaqueductal gray in the rat , 2000, The Journal of comparative neurology.

[17]  Richard Bandler,et al.  Central circuits mediating patterned autonomic activity during active vs. passive emotional coping , 2000, Brain Research Bulletin.

[18]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[19]  I. Izquierdo,et al.  Pharmacological differences between memory consolidation of habituation to an open field and inhibitory avoidance learning. , 2001, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[20]  F. Graeff Serotonin, the periaqueductal gray and panic , 2004, Neuroscience & Biobehavioral Reviews.

[21]  R. Paxton The human brain stem and cerebellum , 1995, Neuroradiology.

[22]  P. Corr,et al.  A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance , 2004, Neuroscience & Biobehavioral Reviews.

[23]  Joseph E LeDoux,et al.  Extinction Learning in Humans Role of the Amygdala and vmPFC , 2004, Neuron.

[24]  Howard L Fields,et al.  Glutamatergic activation of anterior cingulate cortex produces an aversive teaching signal , 2004, Nature Neuroscience.

[25]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[26]  S. Maier,et al.  Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus , 2005, Nature Neuroscience.

[27]  J. Price,et al.  Free will versus survival: Brain systems that underlie intrinsic constraints on behavior , 2005, The Journal of comparative neurology.

[28]  G. Pagnoni,et al.  Neurobiological Substrates of Dread , 2006, Science.

[29]  P. Lang,et al.  Emotion, motivation, and the brain: reflex foundations in animal and human research. , 2006, Progress in brain research.

[30]  Almut Engelien,et al.  Increased brainstem volume in panic disorder: a voxel-based morphometric study , 2006, Neuroreport.

[31]  Irene Tracey,et al.  Determining anatomical connectivities between cortical and brainstem pain processing regions in humans: A diffusion tensor imaging study in healthy controls , 2006, Pain.

[32]  M. Walton,et al.  A Role for the Macaque Anterior Cingulate Gyrus in Social Valuation , 2006, Science.

[33]  Siamak Shahidi,et al.  BRAIN RES BULL , 2008 .

[34]  S. Bloom Understanding Trauma: Integrating Biological, Clinical and Cultural Perspectives , 2008 .