Modulating amygdala responses to emotion: Evidence from pharmacological fMRI

The use of functional MRI (fMRI) in combination with pharmacological challenges has increased exponentially in recent years, motivated by the idea not only to elucidate the neurochemical foundations of human emotional and cognitive faculties, but also to optimize human brain function in healthy individuals and identify novel drug targets, with the ultimate goal to design more specific pharmacological therapies for the various disorders of human emotion and cognition. In particular, emotional responding of the amygdala has become a central interest, and pharmacological fMRI has been used to specifically probe, and modulate, amygdala activation in response to facial expressions of emotion and emotionally laden scenes. This article reviews recent fMRI experiments manipulating the amygdala's physiological response to such stimuli by pharmacological means and lays a particular focus on monoaminergic, glutamatergic, GABAergic, and hormonal/peptidergic challenges.

[1]  Sabine C. Herpertz,et al.  Effects of intranasal oxytocin on emotional face processing in women , 2010, Psychoneuroendocrinology.

[2]  R. Dolan,et al.  Emotion, Decision Making, and the Amygdala , 2008, Neuron.

[3]  Rebecca Elliott,et al.  The Effect of Citalopram Pretreatment on Neuronal Responses to Neuropsychological Tasks in Normal Volunteers: An fMRI Study , 2005, Neuropsychopharmacology.

[4]  P. Hauri,et al.  A controlled study of alprazolam and propranolol in panic-disordered and agoraphobic outpatients. , 1991, Journal of clinical psychopharmacology.

[5]  C. A. Morgan,et al.  Effects of the beta-blocker propranolol on cued and contextual fear conditioning in humans , 2004, Psychopharmacology.

[6]  A. Meyer-Lindenberg,et al.  Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans , 2009, Molecular Psychiatry.

[7]  L. Swanson The Amygdala and Its Place in the Cerebral Hemisphere , 2003, Annals of the New York Academy of Sciences.

[8]  Danielle S. Bassett,et al.  Corrigendum to “A validated network of effective amygdala connectivity” [NeuroImage 36 (2007) 736–745] , 2008, NeuroImage.

[9]  Malcolm P. Young,,et al.  Analysis of Connectivity: Neural Systems in the Cerebral Cortex , 1994, Reviews in the neurosciences.

[10]  K. Amunts,et al.  Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps , 2005, Anatomy and Embryology.

[11]  W. Young,et al.  Oxytocin: The great facilitator of life , 2009, Progress in Neurobiology.

[12]  Current status of beta-blocking drugs in the treatment of anxiety disorders. , 1988, Drugs.

[13]  A. Meyer-Lindenberg,et al.  5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression , 2005, Nature Neuroscience.

[14]  Michael X. Cohen,et al.  Oxytocin Enhances Amygdala-Dependent, Socially Reinforced Learning and Emotional Empathy in Humans , 2010, The Journal of Neuroscience.

[15]  M. Bourin,et al.  Antidepressant-like activity of selective serotonin reuptake inhibitors combined with a NK1 receptor antagonist in the mouse forced swimming test , 2006, Behavioural Brain Research.

[16]  Catherine J. Harmer,et al.  Effect of a single dose of citalopram on amygdala response to emotional faces , 2009, British Journal of Psychiatry.

[17]  K. Hugdahl,et al.  Effect of beta-receptor blockade on anxiety with reference to the three-systems model of phobic behavior. , 1985, Neuropsychobiology.

[18]  R. Luthringer,et al.  Pharmacological models in healthy volunteers: their use in the clinical development of psychotropic drugs , 2007, Journal of psychopharmacology.

[19]  Christian Büchel,et al.  Oxytocin Attenuates Amygdala Responses to Emotional Faces Regardless of Valence , 2007, Biological Psychiatry.

[20]  Henrik Walter,et al.  Noradrenergic enhancement of amygdala responses to fear. , 2009, Social cognitive and affective neuroscience.

[21]  W. Maier,et al.  Emotion-induced retrograde amnesia varies as a function of noradrenergic-glucocorticoid activity , 2007, Psychopharmacology.

[22]  Adolf Pfefferbaum,et al.  The Human Basal Forebrain Integrates the Old and the New , 2004, Neuron.

[23]  Danielle S. Bassett,et al.  A validated network of effective amygdala connectivity , 2007, NeuroImage.

[24]  K. Kendrick,et al.  The N-Methyl-D-Aspartate Receptor Co-agonist D-Cycloserine Facilitates Declarative Learning and Hippocampal Activity in Humans , 2010, Biological Psychiatry.

[25]  P. Cowen,et al.  Short-term antidepressant treatment modulates amygdala response to happy faces , 2009, Psychopharmacology.

[26]  Juraj Kukolja,et al.  Selective processing of social stimuli in the superficial amygdala , 2009, Human brain mapping.

[27]  Karine Sergerie,et al.  The role of the amygdala in emotional processing: A quantitative meta-analysis of functional neuroimaging studies , 2008, Neuroscience & Biobehavioral Reviews.

[28]  Gereon R. Fink,et al.  Modeling a Negative Response Bias in the Human Amygdala by Noradrenergic–Glucocorticoid Interactions , 2008, The Journal of Neuroscience.

[29]  Jonathan D. Cohen,et al.  An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. , 2005, Annual review of neuroscience.

[30]  K. Kendrick,et al.  Human amygdala reactivity is diminished by the β-noradrenergic antagonist propranolol , 2010, Psychological Medicine.

[31]  E. Byrnes,et al.  Enhanced maternal aggression and associated changes in neuropeptide gene expression in multiparous rats. , 2009, Behavioral neuroscience.

[32]  C. Brantigan,et al.  Effect of beta blockade and beta stimulation on stage fright. , 1982, The American journal of medicine.

[33]  G. Quirk,et al.  Systemic Propranolol Acts Centrally to Reduce Conditioned Fear in Rats Without Impairing Extinction , 2009, Biological Psychiatry.

[34]  V. K. Jensen,et al.  "The effect of beta blockade on stress-induced cognitive dysfunction in adolescents". , 1991, Clinical pediatrics.

[35]  Yoshiro Okubo,et al.  Effects of dopaminergic and serotonergic manipulation on emotional processing: A pharmacological fMRI study , 2005, NeuroImage.

[36]  H. Faigel The Effect of Beta Blockade on Stress-Induced Cognitive Dysfunction in Adolescents , 1991, Clinical pediatrics.

[37]  J. Krystal,et al.  A Meta-analysis of D-cycloserine and the Facilitation of Fear Extinction and Exposure Therapy , 2022 .

[38]  D J Woodward,et al.  Modulatory actions of norepinephrine on neural circuits. , 1991, Advances in experimental medicine and biology.

[39]  G. McCarthy,et al.  Dynamic perception of facial affect and identity in the human brain. , 2003, Cerebral Cortex.

[40]  J. Kuhlmann,et al.  The applications of biomarkers in early clinical drug development to improve decision-making processes. , 2006, Current clinical pharmacology.

[41]  John F. Disterhoft,et al.  Hippocampus-dependent learning facilitated by a monoclonal antibody or D-cycloserine , 1992, Nature.

[42]  Markus Heinrichs,et al.  Oxytocin, vasopressin, and human social behavior , 2009, Frontiers in Neuroendocrinology.

[43]  Francesco Fera,et al.  Dextroamphetamine Modulates the Response of the Human Amygdala , 2002, Neuropsychopharmacology.

[44]  K. J. Parker,et al.  Preliminary evidence that plasma oxytocin levels are elevated in major depression , 2010, Psychiatry Research.

[45]  Guillén Fernández,et al.  Testosterone reduces amygdala–orbitofrontal cortex coupling , 2010, Psychoneuroendocrinology.

[46]  U. Fischbacher,et al.  Oxytocin increases trust in humans , 2005, Nature.

[47]  Christian Keysers,et al.  The BOLD signal in the amygdala does not differentiate between dynamic facial expressions. , 2007, Social cognitive and affective neuroscience.

[48]  M. Joëls Corticosteroid effects in the brain: U-shape it. , 2006, Trends in pharmacological sciences.

[49]  S. Orr,et al.  The effects of vasopressin on human facial responses related to social communication , 2004, Psychoneuroendocrinology.

[50]  A. Grace,et al.  Noradrenergic modulation of basolateral amygdala neuronal activity: opposing influences of alpha-2 and beta receptor activation. , 2007, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[51]  Peter Kirsch,et al.  Oxytocin Modulates Neural Circuitry for Social Cognition and Fear in Humans , 2005, The Journal of Neuroscience.

[52]  J. D. McGaugh Memory--a century of consolidation. , 2000, Science.

[53]  E. Bullmore,et al.  Human pharmacological MRI. , 2004, Trends in pharmacological sciences.

[54]  E. Amaro,et al.  Neural activity changes to emotional stimuli in healthy individuals under chronic use of clomipramine , 2010, Journal of psychopharmacology.

[55]  Christian Büchel,et al.  Different amygdala subregions mediate valence-related and attentional effects of oxytocin in humans , 2010, Proceedings of the National Academy of Sciences.

[56]  Dean F Wong,et al.  The Role of Imaging in Proof of Concept for CNS Drug Discovery and Development , 2009, Neuropsychopharmacology.

[57]  Martin Keller,et al.  The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) surveys , 2003, International journal of methods in psychiatric research.

[58]  A. Grace,et al.  Noradrenergic Modulation of Basolateral Amygdala Neuronal Activity: Opposing Influences of α-2 and β Receptor Activation , 2007, The Journal of Neuroscience.

[59]  M. Ohsawa,et al.  Effects of serotonergic anxiolytics on the freezing behavior in the elevated open-platform test in mice. , 2007, Journal of pharmacological sciences.

[60]  Frieder Keller,et al.  Pharmacokinetics and Pharmacodynamics of Systemically Administered Glucocorticoids , 2005, Clinical Pharmacokinetics.

[61]  A. Simmons,et al.  Escitalopram effects on insula and amygdala BOLD activation during emotional processing , 2008, Psychopharmacology.

[62]  Rebecca Elliott,et al.  Citalopram modulation of neuronal responses to aversive face emotions: a functional MRI study , 2007, Neuroreport.

[63]  Alois Saria,et al.  Substance P in the medial amygdala: Emotional stress-sensitive release and modulation of anxiety-related behavior in rats , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[64]  P. Veinante,et al.  Vasopressin and Oxytocin Excite Distinct Neuronal Populations in the Central Amygdala , 2005, Science.

[65]  Anders Björklund,et al.  The primate nervous system , 1997 .

[66]  H. Barbas,et al.  Anatomic basis of cognitive-emotional interactions in the primate prefrontal cortex , 1995, Neuroscience & Biobehavioral Reviews.

[67]  O. Blin,et al.  Effect of Levodopa on Healthy Volunteers' Facial Emotion Perception: An fMRI Study , 2005, Clinical neuropharmacology.

[68]  T. Bliss,et al.  Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path , 1973, The Journal of physiology.

[69]  C. Carter,et al.  Diminished plasma oxytocin in schizophrenic patients with neuroendocrine dysfunction and emotional deficits , 2008, Schizophrenia Research.

[70]  R. Hurlemann Noradrenergic–glucocorticoid mechanisms in emotion-induced amnesia: from adaptation to disease , 2008, Psychopharmacology.

[71]  Carl Feinstein,et al.  Oxytocin and autistic disorder: alterations in peptide forms , 2001, Biological Psychiatry.

[72]  L. Swanson,et al.  What is the amygdala? , 1998, Trends in Neurosciences.

[73]  Madalina E. Tivarus,et al.  Beta-adrenergic Modulation of Cognitive Flexibility during Stress , 2007, Journal of Cognitive Neuroscience.

[74]  Michael Angstadt,et al.  Beyond threat: Amygdala reactivity across multiple expressions of facial affect , 2006, NeuroImage.

[75]  C. Feinstein,et al.  Plasma oxytocin levels in autistic children , 1998, Biological Psychiatry.

[76]  Olga V. Demler,et al.  The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). , 2003, JAMA.

[77]  P. Cowen,et al.  NK1 receptor antagonism and the neural processing of emotional information in healthy volunteers. , 2009, The international journal of neuropsychopharmacology.

[78]  L. Pessoa On the relationship between emotion and cognition , 2008, Nature Reviews Neuroscience.

[79]  J. Monahan,et al.  d-Cycloserine: A ligand for the N-methyl-d-aspartate coupled glycine receptor has partial agonist characteristics , 1989, Neuroscience Letters.

[80]  Patrick M Fisher,et al.  Acute 5-HT Reuptake Blockade Potentiates Human Amygdala Reactivity , 2008, Neuropsychopharmacology.

[81]  E. Phelps Human emotion and memory: interactions of the amygdala and hippocampal complex , 2004, Current Opinion in Neurobiology.

[82]  Caroline F. Zink,et al.  Vasopressin Modulates Medial Prefrontal Cortex–Amygdala Circuitry during Emotion Processing in Humans , 2010, The Journal of Neuroscience.

[83]  Justin S. Feinstein,et al.  Dose-dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing. , 2005, Archives of general psychiatry.

[84]  T. Insel,et al.  Oxytocin in the Medial Amygdala is Essential for Social Recognition in the Mouse , 2001, The Journal of Neuroscience.

[85]  J. Leppänen Emotional information processing in mood disorders: a review of behavioral and neuroimaging findings , 2006, Current opinion in psychiatry.

[86]  Danielle M. Williams,et al.  D-cycloserine Inhibits Amygdala Responses During Repeated Presentations of Faces , 2007, CNS Spectrums.

[87]  Rick Richardson,et al.  Effects of D-Cycloserine on Extinction: Translation From Preclinical to Clinical Work , 2006, Biological Psychiatry.

[88]  P. Lang International Affective Picture System (IAPS) : Technical Manual and Affective Ratings , 1995 .

[89]  Stefano Bonassi,et al.  Biomarkers in molecular epidemiology studies for health risk prediction. , 2002, Mutation research.

[90]  Siegfried Kasper,et al.  Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: A randomized cross-over study , 2010, NeuroImage.

[91]  Guy M. Goodwin,et al.  Antidepressant Drug Treatment Modifies the Neural Processing of Nonconscious Threat Cues , 2006, Biological Psychiatry.

[92]  Stefan Klöppel,et al.  The NMDA Agonist D-Cycloserine Facilitates Fear Memory Consolidation in Humans , 2008, Cerebral cortex.

[93]  O. Blin,et al.  Amygdala Activation Modulated by Levodopa During Emotional Recognition Processing in Healthy Volunteers: A Double-Blind, Placebo-Controlled Study , 2007, Journal of clinical psychopharmacology.

[94]  P. Milgrom,et al.  Effect of a Beta-adrenergic Blocking Agent on Dental Anxiety , 1991, Journal of dental research.

[95]  Takeshi Inoue,et al.  Effect of combined treatment with noradrenaline and serotonin reuptake inhibitors on conditioned freezing. , 2006, European journal of pharmacology.

[96]  P. Tyrer Current Status of β-Blocking Drugs in the Treatment of Anxiety Disorders , 1988, Drugs.

[97]  Marchell E. Thurow,et al.  Cortisol variation in humans affects memory for emotionally laden and neutral information. , 2003, Behavioral neuroscience.

[98]  Michael Davis,et al.  The amygdala , 2000, Current Biology.

[99]  Bruce S. McEwen,et al.  Stress, memory and the amygdala , 2009, Nature Reviews Neuroscience.

[100]  Frederik Barkhof,et al.  Noradrenaline mediates amygdala activation in men and women during encoding of emotional material , 2005, NeuroImage.

[101]  Erno J. Hermans,et al.  Exogenous Testosterone Enhances Responsiveness to Social Threat in the Neural Circuitry of Social Aggression in Humans , 2008, Biological Psychiatry.

[102]  Clare E Mackay,et al.  Short-term antidepressant treatment and facial processing , 2007, British Journal of Psychiatry.

[103]  O. Benkert,et al.  KOMPENDIUM DER PSYCHIATRISCHEN PHARMAKOTHERAPIE , 1998 .

[104]  John Patrick Aggleton,et al.  The Amygdala : a functional analysis , 2000 .

[105]  C. Berridge,et al.  The locus coeruleus–noradrenergic system: modulation of behavioral state and state-dependent cognitive processes , 2003, Brain Research Reviews.