Neuroimaging Studies of Amygdala Function in Anxiety Disorders

Abstract: Neuroimaging research has helped to advance neurobiological models of anxiety disorders. The amygdala is known to play an important role in normal fear conditioning and is implicated in the pathophysiology of anxiety disorders. The amygdala may also be a target for the beneficial effects of cognitive‐behavioral and medication treatments for anxiety disorders. In the current paper, we review neuroimaging research pertaining to the role of the amygdala in anxiety disorders and their treatment. Moreover, we discuss the development of new neuroimaging paradigms for measuring aspects of amygdala function, as well as the function of related brain regions. We conclude that such tools hold great promise for facilitating progress in relevant basic neuroscience as well as clinical research domains.

[1]  M. Bradley,et al.  Neuroanatomical correlates of pleasant and unpleasant emotion , 1997, Neuropsychologia.

[2]  J. Kagan,et al.  Further evidence of an association between behavioral inhibition and anxiety disorders: Results from a family study of children from a non-clinical sample , 1991 .

[3]  R W Neufeld,et al.  A short echo 1H spectroscopy and volumetric MRI study of the corpus striatum in patients with obsessive-compulsive disorder and comparison subjects. , 1998, The American journal of psychiatry.

[4]  J. Mazziotta,et al.  Cerebral glucose metabolic rates in nondepressed patients with obsessive-compulsive disorder. , 1988, The American journal of psychiatry.

[5]  N. Schuff,et al.  Decreased hippocampal N-acetylaspartate in the absence of atrophy in posttraumatic stress disorder , 2001, Biological Psychiatry.

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

[7]  N. Alpert,et al.  Probing striatal function in obsessive-compulsive disorder: a PET study of implicit sequence learning. , 1997, The Journal of neuropsychiatry and clinical neurosciences.

[8]  S. Rauch,et al.  Differential prefrontal cortex and amygdala habituation to repeatedly presented emotional stimuli , 2001, Neuroreport.

[9]  S. Posse,et al.  Two-dimensional proton echo-planar spectroscopic imaging of brain metabolic changes during lactate-induced panic. , 1999, Archives of general psychiatry.

[10]  V S Caviness,et al.  Cerebral structural abnormalities in obsessive-compulsive disorder. A quantitative morphometric magnetic resonance imaging study. , 1996, Archives of general psychiatry.

[11]  D. Rosenberg,et al.  Case study: caudate glutamatergic changes with paroxetine therapy for pediatric obsessive-compulsive disorder. , 1998, Journal of the American Academy of Child and Adolescent Psychiatry.

[12]  R. McNally.  Experimental approaches to cognitive abnormality in posttraumatic stress disorder. , 1998, Clinical psychology review.

[13]  S. Rauch,et al.  Striatal recruitment during an implicit sequence learning task as measured by functional magnetic resonance imaging , 1997, Human brain mapping.

[14]  S. Southwick,et al.  MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. , 1995, The American journal of psychiatry.

[15]  P Pietrini,et al.  Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy. , 1992, Archives of general psychiatry.

[16]  M. Stein,et al.  Hippocampal volume in women victimized by childhood sexual abuse , 1997, Psychological Medicine.

[17]  A. Pitkänen,et al.  Abnormal regional benzodiazepine receptor uptake in the prefrontal cortex in patients with panic disorder , 1995, Nuclear medicine communications.

[18]  D. Rosenberg,et al.  Proton spectroscopic imaging of the thalamus in treatment-naive pediatric obsessive–compulsive disorder∗ , 2000, Biological Psychiatry.

[19]  J. Rapoport,et al.  Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. , 1989, Archives of general psychiatry.

[20]  F Fazio,et al.  [18F]FDG PET Study in Obsessive–Compulsive Disorder , 1995, British Journal of Psychiatry.

[21]  Lisa M Shin,et al.  Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study , 2000, Biological Psychiatry.

[22]  R. Bronen,et al.  Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse—a preliminary report , 1997, Biological Psychiatry.

[23]  Karl J. Friston,et al.  Neural responses to salient visual stimuli , 1997, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[24]  E. Smeraldi,et al.  Increased right caudate nucleus size in obsessive-compulsive disorder: Detection with magnetic resonance imaging , 1992, Psychiatry Research: Neuroimaging.

[25]  S. Rauch,et al.  Neuroimaging and the Neuroanatomy of Posttraumatic Stress Disorder , 1998, CNS Spectrums.

[26]  S. Woods,et al.  YOHIMBINE ALTERS REGIONAL CEREBRAL BLOOD FLOW IN PANIC DISORDER , 1988, The Lancet.

[27]  R. McNally,et al.  Cognitive processing of idiographic emotional information in panic disorder. , 1994, Behaviour research and therapy.

[28]  Michael E Phelps,et al.  FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder , 1998, Psychiatry Research: Neuroimaging.

[29]  M. Bradley,et al.  Looking at pictures: affective, facial, visceral, and behavioral reactions. , 1993, Psychophysiology.

[30]  George Bush,et al.  The emotional counting stroop paradigm: a functional magnetic resonance imaging probe of the anterior cingulate affective division , 1998, Biological Psychiatry.

[31]  C D Frith,et al.  Functional Anatomy of Obsessive–Compulsive Phenomena , 1994, British Journal of Psychiatry.

[32]  T. Nordahl,et al.  Cerebral glucose metabolic rates in obsessive compulsive disorder. , 1989, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[33]  M. Raichle,et al.  PET images of blood flow changes during anxiety: correction. , 1992, Science.

[34]  M. Mintun,et al.  Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study , 2001, Biological Psychiatry.

[35]  D. Rosenberg,et al.  Thalamic volume in pediatric obsessive–compulsive disorder patients before and after cognitive behavioral therapy , 2000, Biological Psychiatry.

[36]  M E Phelps,et al.  Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder. , 1996, Archives of general psychiatry.

[37]  N. Alpert,et al.  A positron emission tomographic study of simple phobic symptom provocation. , 1995, Archives of general psychiatry.

[38]  M. Stein,et al.  A brain single photon-emission computed tomography (SPECT) study of generalized social phobia , 1996, Biological Psychiatry.

[39]  S. Southwick,et al.  Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder. , 1999, The American journal of psychiatry.

[40]  J. Mazziotta,et al.  Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. , 1992, Archives of general psychiatry.

[41]  K. Frustaci,et al.  A pilot longitudinal study of hippocampal volumes in pediatric maltreatment-related posttraumatic stress disorder , 2001, Biological Psychiatry.

[42]  J. Pierri,et al.  Frontostriatal measurement in treatment-naive children with obsessive-compulsive disorder. , 1997, Archives of general psychiatry.

[43]  Håkan Fischer,et al.  Enhanced amygdala responses to emotional versus neutral schematic facial expressions , 2002, Neuroreport.

[44]  S. Rauch,et al.  Masked Presentations of Emotional Facial Expressions Modulate Amygdala Activity without Explicit Knowledge , 1998, The Journal of Neuroscience.

[45]  S. Alborzian,et al.  Localized Orbitofrontal and Subcortical Metabolic Changes and Predictors of Response to Paroxetine Treatment in Obsessive-Compulsive Disorder , 1999, Neuropsychopharmacology.

[46]  M E Raichle,et al.  The application of positron emission tomography to the study of panic disorder. , 1986, The American journal of psychiatry.

[47]  Ravi S. Menon,et al.  Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation. , 2001, The American journal of psychiatry.

[48]  R. Rubin,et al.  Regional xenon 133 cerebral blood flow and cerebral technetium 99m HMPAO uptake in unmedicated patients with obsessive-compulsive disorder and matched normal control subjects. Determination by high-resolution single-photon emission computed tomography. , 1992, Archives of general psychiatry.

[49]  E. Maguire,et al.  Methods for developmental studies of fear conditioning circuitry , 2001, Biological Psychiatry.

[50]  R. Sapolsky,et al.  Hippocampal damage associated with prolonged glucocorticoid exposure in primates , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[51]  A J Rush,et al.  Cerebral blood flow changes during sodium-lactate-induced panic attacks. , 1988, The American journal of psychiatry.

[52]  J. Mazziotta,et al.  Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls. , 1987, Archives of general psychiatry.

[53]  Mats Fredrikson,et al.  A functional cerebral response to frightening visual stimulation , 1993, Psychiatry Research: Neuroimaging.

[54]  Alan C. Evans,et al.  Functional neuroanatomy of CCK4-induced anxiety in normal healthy volunteers. , 1995, The American journal of psychiatry.

[55]  S. Rauch,et al.  Response and Habituation of the Human Amygdala during Visual Processing of Facial Expression , 1996, Neuron.

[56]  Murray B Stein,et al.  Regional cerebral metabolic asymmetries replicated in an independent group of patients with panic disorder , 1998, Biological Psychiatry.

[57]  G. Pearlson,et al.  Effects of fluoxetine on regional cerebral blood flow in obsessive-compulsive patients. , 1991, The American journal of psychiatry.

[58]  Alberto Pupi,et al.  Brain perfusion abnormalities in drug-naive, lactate-sensitive panic patients: A SPECT study , 1993, Biological Psychiatry.

[59]  J. Tiihonen,et al.  Dopamine reuptake site densities in patients with social phobia. , 1997, The American journal of psychiatry.

[60]  S M Kosslyn,et al.  Visual imagery and perception in posttraumatic stress disorder. A positron emission tomographic investigation. , 1997, Archives of general psychiatry.

[61]  M. Lowe,et al.  Human amygdala activation detected with echo-planar functional magnetic resonance imaging. , 1996, Neuroreport.

[62]  H Fischer,et al.  Affective and attentive neural networks in humans: a PET study of Pavlovian conditioning , 1995, Neuroreport.

[63]  Sylvain Houle,et al.  Neuroanatomic correlates of CCK-4-induced panic attacks in healthy humans: a comparison of two time points , 1999, Biological Psychiatry.

[64]  Karl J. Friston,et al.  Brain Systems Mediating Aversive Conditioning: an Event-Related fMRI Study , 1998, Neuron.

[65]  S. Rauch,et al.  The counting stroop: An interference task specialized for functional neuroimaging—validation study with functional MRI , 1998, Human brain mapping.

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

[67]  S. Kosslyn,et al.  A PET investigation of implicit and explicit sequence learning , 1995 .

[68]  G D Pearlson,et al.  Elevated medial-frontal cerebral blood flow in obsessive-compulsive patients: a SPECT study. , 1991, The American journal of psychiatry.

[69]  R. Lydiard,et al.  Brain circuits in panic disorder , 1998, Biological Psychiatry.

[70]  D. Perrett,et al.  A differential neural response in the human amygdala to fearful and happy facial expressions , 1996, Nature.

[71]  S. Stone-Elander,et al.  Functional neuroanatomy of visually elicited simple phobic fear: additional data and theoretical analysis. , 1995, Psychophysiology.

[72]  Stephan Eliez,et al.  Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder , 2001, Biological Psychiatry.

[73]  O. Speck,et al.  1H-magnetic resonance spectroscopy in obsessive-compulsive disorder: evidence for neuronal loss in the cingulate gyrus and the right striatum , 1997, Psychiatry Research: Neuroimaging.

[74]  Joseph E LeDoux,et al.  Human Amygdala Activation during Conditioned Fear Acquisition and Extinction: a Mixed-Trial fMRI Study , 1998, Neuron.

[75]  J. R. Baker,et al.  Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder. , 1996, Archives of general psychiatry.

[76]  T Greitz,et al.  Regional cerebral blood flow during experimental phobic fear. , 2007, Psychophysiology.

[77]  S. Rauch,et al.  A functional MRI study of human amygdala responses to facial expressions of fear versus anger. , 2001, Emotion.

[78]  N. Alpert,et al.  A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery. , 1996, Archives of general psychiatry.

[79]  H Fischer,et al.  Cerebral blood flow in subjects with social phobia during stressful speaking tasks: a PET study. , 2001, The American journal of psychiatry.

[80]  E. Aylward,et al.  Normal caudate nucleus in obsessive-compulsive disorder assessed by quantitative neuroimaging. , 1996, Archives of general psychiatry.

[81]  C. Brandt,et al.  Increased benzodiazepine receptor density in the prefrontal cortex in patients with panic disorder , 1998, Journal of Neural Transmission.

[82]  Lawrence H Staib,et al.  Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study , 1999, Biological Psychiatry.

[83]  M. Keshavan,et al.  Decrease in thalamic volumes of pediatric patients with obsessive-compulsive disorder who are taking paroxetine. , 2000, Archives of general psychiatry.

[84]  M E Shenton,et al.  Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD. , 2001, The American journal of psychiatry.

[85]  Karl J. Friston,et al.  Amygdala–Hippocampal Involvement in Human Aversive Trace Conditioning Revealed through Event-Related Functional Magnetic Resonance Imaging , 1999, The Journal of Neuroscience.

[86]  N. Alpert,et al.  Conscious recollection and the human hippocampal formation: evidence from positron emission tomography. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[87]  H Fischer,et al.  Differential response in the human amygdala to racial outgroup vs ingroup face stimuli , 2000, Neuroreport.

[88]  Nick Medford,et al.  Time courses of left and right amygdalar responses to fearful facial expressions , 2001 .

[89]  N. Alpert,et al.  Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. , 1994, Archives of general psychiatry.

[90]  T. Richards,et al.  Proton magnetic resonance spectroscopy investigation of hyperventilation in subjects with panic disorder and comparison subjects. , 1995, The American journal of psychiatry.

[91]  J M Gorman,et al.  Cerebral glucose metabolism in women with panic disorder. , 1998, The American journal of psychiatry.

[92]  M. Stein,et al.  Cerebral glucose metabolic differences in patients with panic disorder. , 1990, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[93]  U Klose,et al.  fMRI reveals amygdala activation to human faces in social phobics , 1998, Neuroreport.

[94]  A. Fyer,et al.  Current approaches to etiology and pathophysiology of specific phobia , 1998, Biological Psychiatry.

[95]  R. Kikinis,et al.  Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder , 1996, Biological Psychiatry.

[96]  Israel Liberzon,et al.  Brain activation in PTSD in response to trauma-related stimuli , 1999, Biological Psychiatry.

[97]  M Ashtari,et al.  Orbital frontal and amygdala volume reductions in obsessive-compulsive disorder. , 1999, Archives of general psychiatry.

[98]  S. Kosslyn,et al.  Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation. , 1999, The American journal of psychiatry.

[99]  H Fischer,et al.  The amygdala and individual differences in human fear conditioning , 1997, Neuroreport.

[100]  M Ashtari,et al.  Reduced caudate nucleus volume in obsessive-compulsive disorder. , 1995, Archives of general psychiatry.

[101]  P. Murali Doraiswamy,et al.  Magnetic resonance imaging in social phobia , 1994, Psychiatry Research.

[102]  M. Stein.  Neurobiological perspectives on social phobia: from affiliation to zoology , 1998, Biological Psychiatry.

[103]  D. Murphy,et al.  Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Patients treated with clomipramine. , 1990, Archives of general psychiatry.

[104]  Wolfgang Grodd,et al.  Subcortical correlates of differential classical conditioning of aversive emotional reactions in social phobia , 1999, Biological Psychiatry.

[105]  V J Cunningham,et al.  Decreased brain GABA(A)-benzodiazepine receptor binding in panic disorder: preliminary results from a quantitative PET study. , 1998, Archives of general psychiatry.

[106]  Kenneth S Kendler,et al.  The etiology of phobias: an evaluation of the stress-diathesis model. , 2002, Archives of general psychiatry.

[107]  J. Andersson,et al.  Brain correlates of an unexpected panic attack: a human positron emission tomographic study , 1998, Neuroscience Letters.

[108]  S. Rauch,et al.  An fMRI study of anterior cingulate function in posttraumatic stress disorder , 2001, Biological Psychiatry.