The Biology of Fear

Each of us has felt afraid, and we can all recognize fear in many animal species. Yet there is no consensus in the scientific study of fear. Some argue that 'fear' is a psychological construct rather than something discoverable through scientific investigation. Others argue that the term 'fear' cannot properly be applied to animals because we cannot know whether they feel afraid. Studies in rodents show that there are highly specific brain circuits for fear, whereas findings from human neuroimaging seem to make the opposite claim. Here, I review the field and urge three approaches that could reconcile the debates. For one, we need a broadly comparative approach that would identify core components of fear conserved across phylogeny. This also pushes us towards the second point of emphasis: an ecological theory of fear that is essentially functional. Finally, we should aim even to incorporate the conscious experience of being afraid, reinvigorating the study of feelings across species.

[1]  C. Mervis,et al.  Duplication of GTF2I results in separation anxiety in mice and humans. , 2012, American journal of human genetics.

[2]  Joseph E LeDoux,et al.  From Fear to Safety and Back: Reversal of Fear in the Human Brain , 2008, The Journal of Neuroscience.

[3]  Rony Paz,et al.  Auditory aversive learning increases discrimination thresholds , 2011, Nature Neuroscience.

[4]  David J. Anderson,et al.  Functional identification of an aggression locus in the mouse hypothalamus , 2010, Nature.

[5]  Sheng He,et al.  Cortical Responses to Invisible Faces: Dissociating Subsystems for Facial-Information Processing , 2006, Current Biology.

[6]  P. Lang,et al.  Affective judgment and psychophysiological response: Dimensional covariation in the evaluation of pictorial stimuli. , 1989 .

[7]  C. Grillon,et al.  Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety , 2010, Neuropsychopharmacology.

[8]  O. Hikosaka,et al.  Representation of negative motivational value in the primate lateral habenula , 2009, Nature Neuroscience.

[9]  Matthew H. Davis,et al.  Detecting Awareness in the Vegetative State , 2006, Science.

[10]  J. D. McGaugh The amygdala modulates the consolidation of memories of emotionally arousing experiences. , 2004, Annual review of neuroscience.

[11]  Joseph E LeDoux Emotion circuits in the brain. , 2009, Annual review of neuroscience.

[12]  J. Price Comparative Aspects of Amygdala Connectivity , 2003, Annals of the New York Academy of Sciences.

[13]  Paul J. Whalen,et al.  The uncertainty of it all , 2007, Trends in Cognitive Sciences.

[14]  L. F. Barrett Solving the Emotion Paradox: Categorization and the Experience of Emotion , 2006, Personality and social psychology review : an official journal of the Society for Personality and Social Psychology, Inc.

[15]  G. Tononi Consciousness as Integrated Information: a Provisional Manifesto , 2008, The Biological Bulletin.

[16]  M. T. Shipley,et al.  Columnar organization in the midbrain periaqueductal gray: modules for emotional expression? , 1994, Trends in Neurosciences.

[17]  I. Coolen,et al.  Social Learning in Noncolonial Insects? , 2005, Current Biology.

[18]  F. Guimarães,et al.  Involvement of the lateral septal area in the expression of fear conditioning to context. , 2010, Learning & memory.

[19]  E. Azmitia The neuropsychology of anxiety: an enquiry into the functions of the Septo-Hippocampal system, Gray J.A.. Oxford University Press, New York (1981), pp. 523.,£27.50 , 1983 .

[20]  S. Jesuthasan,et al.  Fear, anxiety, and control in the zebrafish , 2012, Developmental neurobiology.

[21]  M. Mendl,et al.  An integrative and functional framework for the study of animal emotion and mood , 2010, Proceedings of the Royal Society B: Biological Sciences.

[22]  David J. Anderson,et al.  Neural Correlates of Competing Fear Behaviors Evoked by an Innately Aversive Stimulus , 2003, The Journal of Neuroscience.

[23]  Daniel P. Kennedy,et al.  Personal Space Regulation by the Human Amygdala , 2009, Nature Neuroscience.

[24]  S. Mineka,et al.  Observational conditioning of snake fear in rhesus monkeys. , 1984, Journal of abnormal psychology.

[25]  M. Kozak,et al.  Emotional processing of fear: exposure to corrective information. , 1986, Psychological bulletin.

[26]  C. Darwin The Expression of the Emotions in Man and Animals , .

[27]  L. Schenberg,et al.  Evidence of a suffocation alarm system within the periaqueductal gray matter of the rat , 2012, Neuroscience.

[28]  Stefan M. Brudzynski,et al.  Principles of Rat Communication: Quantitative Parameters of Ultrasonic Calls in Rats , 2005, Behavior genetics.

[29]  David J. Anderson,et al.  Genetic dissection of an amygdala microcircuit that gates conditioned fear , 2010, Nature.

[30]  N. Costes,et al.  Emotional Responses to Pleasant and Unpleasant Olfactory, Visual, and Auditory Stimuli: a Positron Emission Tomography Study , 2000, The Journal of Neuroscience.

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

[32]  Karl J. Friston,et al.  Neuroanatomical correlates of externally and internally generated human emotion. , 1997, The American journal of psychiatry.

[33]  M. Fendt,et al.  Temporary Inactivation of the Bed Nucleus of the Stria Terminalis But Not of the Amygdala Blocks Freezing Induced by Trimethylthiazoline, a Component of Fox Feces , 2003, The Journal of Neuroscience.

[34]  E. C. Grant,et al.  Human Facial Expression , 1969 .

[35]  R. W. Schulz The Psychology of Fear and Stress , 1974 .

[36]  Lisa Feldman Barrett,et al.  Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies , 2008, NeuroImage.

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

[38]  G. Koob,et al.  Encyclopedia of Behavioral Neuroscience , 2010 .

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

[40]  Roman Feiman,et al.  Expressing fear enhances sensory acquisition , 2008, Nature Neuroscience.

[41]  Daniel P. Kennedy,et al.  The social brain in psychiatric and neurological disorders , 2012, Trends in Cognitive Sciences.

[42]  D. Davies,et al.  Striato-amygdaloid transition area lesions reduce the duration of tonic immobility in the lizard Podarcis hispanica , 2002, Brain Research Bulletin.

[43]  D. Blanchard,et al.  Human defensive behaviors to threat scenarios show parallels to fear- and anxiety-related defense patterns of non-human mammals , 2001, Neuroscience & Biobehavioral Reviews.

[44]  Andreas Olsson,et al.  Learning fears by observing others: the neural systems of social fear transmission. , 2007, Social cognitive and affective neuroscience.

[45]  A. Todorov,et al.  The functional basis of face evaluation , 2008, Proceedings of the National Academy of Sciences.

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

[47]  Seymour Epstein,et al.  Chapter 8 – THE NATURE OF ANXIETY WITH EMPHASIS UPON ITS RELATIONSHIP TO EXPECTANCY1 , 1972 .

[48]  J. Price,et al.  Neurocircuitry of Mood Disorders , 2010, Neuropsychopharmacology.

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

[50]  Angelo Bifone,et al.  A Neural Switch for Active and Passive Fear , 2012, Neuron.

[51]  Charles D. Spielberger,et al.  Anxiety: Current Trends in Theory and Research , 1972 .

[52]  Karl Deisseroth,et al.  Optical activation of lateral amygdala pyramidal cells instructs associative fear learning , 2010, Proceedings of the National Academy of Sciences.

[53]  R. Adolphs,et al.  The human amygdala in social judgment , 1998, Nature.

[54]  J. Russell Core affect and the psychological construction of emotion. , 2003, Psychological review.

[55]  L. Pessoa,et al.  Emotion processing and the amygdala: from a 'low road' to 'many roads' of evaluating biological significance , 2010, Nature Reviews Neuroscience.

[56]  S. Russo,et al.  A standardized protocol for repeated social defeat stress in mice , 2011, Nature Protocols.

[57]  Lisa Feldman Barrett,et al.  Emotions are real. , 2012, Emotion.

[58]  T. Robbins,et al.  Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala , 1997, Nature.

[59]  Kenneth Webb,et al.  Evolution of Communication Simulation of Adaptive Behavior – Project Report , 2004 .

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

[61]  Sara E. Morrison,et al.  Different Time Courses for Learning-Related Changes in Amygdala and Orbitofrontal Cortex , 2011, Neuron.

[62]  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.

[63]  W. James II.—WHAT IS AN EMOTION ? , 1884 .

[64]  M. Bateson,et al.  Anxiety: An Evolutionary Approach , 2011, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[65]  Kristen A. Lindquist,et al.  The brain basis of emotion: A meta-analytic review , 2012, Behavioral and Brain Sciences.

[66]  P. Lang Imagery in therapy: an information processing analysis of fear , 1977 .

[67]  Joseph E LeDoux Rethinking the Emotional Brain , 2012, Neuron.

[68]  P. Ekman,et al.  Strong evidence for universals in facial expressions: a reply to Russell's mistaken critique. , 1994, Psychological bulletin.

[69]  M. Posner The Brain and Emotion , 1999, Nature Medicine.

[70]  J. Grafman,et al.  Focal brain damage protects against post-traumatic stress disorder in combat veterans , 2008, Nature Neuroscience.

[71]  M. Bateson,et al.  Agitated Honeybees Exhibit Pessimistic Cognitive Biases , 2011, Current Biology.

[72]  L. Kaczmarek,et al.  Between-subject transfer of emotional information evokes specific pattern of amygdala activation. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[73]  Larry W Swanson,et al.  Projections from bed nuclei of the stria terminalis, posterior division: Implications for cerebral hemisphere regulation of defensive and reproductive behaviors , 2004, The Journal of comparative neurology.

[74]  N. Canteras,et al.  The many paths to fear , 2012, Nature Reviews Neuroscience.

[75]  Marta I. Garrido,et al.  Functional Evidence for a Dual Route to Amygdala , 2012, Current Biology.

[76]  Joseph E LeDoux,et al.  Different lateral amygdala outputs mediate reactions and actions elicited by a fear-arousing stimulus , 2000, Nature Neuroscience.

[77]  M. Cabanac What is emotion? , 2002, Behavioural Processes.

[78]  H. Okamoto,et al.  Genetic dissection of the zebrafish habenula, a possible switching board for selection of behavioral strategy to cope with fear and anxiety , 2012, Developmental neurobiology.

[79]  J. Schulkin,et al.  From normal fear to pathological anxiety. , 1998, Psychological review.

[80]  Rainer Goebel,et al.  Subcortical Connections to Human Amygdala and Changes following Destruction of the Visual Cortex , 2012, Current Biology.

[81]  D. Mobbs,et al.  Neural activity associated with monitoring the oscillating threat value of a tarantula , 2010, Proceedings of the National Academy of Sciences.

[82]  S. Shelton,et al.  The Role of the Central Nucleus of the Amygdala in Mediating Fear and Anxiety in the Primate , 2004, The Journal of Neuroscience.

[83]  J. Panksepp Affective consciousness: Core emotional feelings in animals and humans , 2005, Consciousness and Cognition.

[84]  Neural Substrates of Unconditioned Fear, Defense, and Anxiety , 2010 .

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

[86]  Matthew A. Howard,et al.  The Amygdala Is a Chemosensor that Detects Carbon Dioxide and Acidosis to Elicit Fear Behavior , 2009, Cell.

[87]  Asaid Khateb,et al.  Discriminating emotional faces without primary visual cortices involves the right amygdala , 2005, Nature Neuroscience.

[88]  J. O'Doherty,et al.  Automatic and intentional brain responses during evaluation of trustworthiness of faces , 2002, Nature Neuroscience.

[89]  R. Dantzer The Psychology of Fear and Stress, J.A. Gray (Ed.). Cambridge University Press, Cambridge (1987), viii and 422 pp, ISBN 0-521-27098-7 , 1989 .

[90]  Ezequiel A. Di Paolo,et al.  The Design of Animal Communication , 2000, Adapt. Behav..

[91]  J. Talbott Prevalence, Severity, and Comorbidity of 12-Month DSM-IV Disorders in the National Comorbidity Survey Replication , 2006 .

[92]  Katherine Vytal,et al.  Neuroimaging Support for Discrete Neural Correlates of Basic Emotions: A Voxel-based Meta-analysis , 2010, Journal of Cognitive Neuroscience.

[93]  Anil K. Seth,et al.  Consciousness and Complexity , 2022 .

[94]  Peter Marler,et al.  Semantics of an avian alarm call system: the male domestic fowl , 1987 .

[95]  P. Marler,et al.  Monkey responses to three different alarm calls: evidence of predator classification and semantic communication. , 1980, Science.

[96]  A. Todorov,et al.  Shared perceptual basis of emotional expressions and trustworthiness impressions from faces. , 2009, Emotion.

[97]  K. Scherer The dynamic architecture of emotion: Evidence for the component process model , 2009 .

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

[99]  Justin S. Feinstein,et al.  The Human Amygdala and the Induction and Experience of Fear , 2011, Current Biology.

[100]  Stephan Hamann,et al.  Mapping discrete and dimensional emotions onto the brain: controversies and consensus , 2012, Trends in Cognitive Sciences.

[101]  A. Moors Theories of emotion causation: A review , 2009 .

[102]  R. Gerlai,et al.  Alarm substance induced behavioral responses in zebrafish (Danio rerio) , 2008, Behavioural Brain Research.

[103]  John M Hoffman,et al.  Ecstasy and Agony: Activation of the Human Amygdala in Positive and Negative Emotion , 2002, Psychological science.

[104]  Nathaniel M. Alpert,et al.  The functional neuroanatomy of anxiety: a study of three disorders using positron emission tomography and symptom provocation , 1997, Biological Psychiatry.

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

[106]  Lief E. Fenno,et al.  Amygdala circuitry mediating reversible and bidirectional control of anxiety , 2011, Nature.

[107]  D C Blanchard,et al.  Defensive behavior of laboratory and wild Rattus norvegicus. , 1986, Journal of comparative psychology.

[108]  Susana Q. Lima,et al.  Silence resulting from the cessation of movement signals danger , 2012, Current Biology.

[109]  Joseph E LeDoux Evolution of human emotion: a view through fear. , 2012, Progress in brain research.

[110]  J. Price,et al.  The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. , 2000, Cerebral cortex.

[111]  R. Zatorre,et al.  Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[112]  Joseph J. Paton,et al.  The primate amygdala represents the positive and negative value of visual stimuli during learning , 2006, Nature.

[113]  R. Adolphs,et al.  Annals of the New York Academy of Sciences What Does the Amygdala Contribute to Social Cognition? , 2022 .

[114]  D. Skuse,et al.  The Amygdala and Development of the Social Brain , 2003, Annals of the New York Academy of Sciences.

[115]  David J. Anderson,et al.  A single population of olfactory sensory neurons mediates an innate avoidance behaviour in Drosophila , 2004, Nature.

[116]  R. Adolphs,et al.  Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala , 1994, Nature.

[117]  K. Scherer Psychological models of emotion. , 2000 .

[118]  E. Phelps,et al.  The human amygdala. , 2009 .

[119]  B. Baars Global workspace theory of consciousness: toward a cognitive neuroscience of human experience. , 2005, Progress in brain research.

[120]  R. Dolan,et al.  Distant influences of amygdala lesion on visual cortical activation during emotional face processing , 2004, Nature Neuroscience.

[121]  A. Boissy Fear and Fearfulness in Animals , 1995, The Quarterly Review of Biology.

[122]  D. Blanchard,et al.  Attack and defense in rodents as ethoexperimental models for the study of emotion , 1989, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[123]  J. H. Curtis,et al.  Learning Theory and Behavior , 1960 .

[124]  A. Damasio The Feeling of What Happens: Body and Emotion in the Making of Consciousness , 1999 .

[125]  D. Blanchard,et al.  The characterization and modelling of antipredator defensive behavior , 1990, Neuroscience & Biobehavioral Reviews.

[126]  A. Craig,et al.  Interoception and Emotion : a Neuroanatomical Perspective , 2007 .

[127]  Mauricio R. Delgado,et al.  Overlapping neural systems mediating extinction, reversal and regulation of fear , 2010, Trends in Cognitive Sciences.

[128]  D. Amaral,et al.  Amygdalectomy and responsiveness to novelty in rhesus monkeys (Macaca mulatta): generality and individual consistency of effects. , 2006, Emotion.

[129]  A. Anderson,et al.  Emotional memory: What does the amygdala do? , 1997, Current Biology.

[130]  R. Hen,et al.  Genetic approaches to the study of anxiety. , 2004, Annual review of neuroscience.

[131]  P. Ekman An argument for basic emotions , 1992 .

[132]  Klaus Scheffler,et al.  Rising sound intensity: an intrinsic warning cue activating the amygdala. , 2008, Cerebral cortex.

[133]  J. Panksepp,et al.  Review: The Feeling of What Happens: Body and Emotion in the Making of Consciousness , 2000 .

[134]  A. Lüthi,et al.  Processing of Temporal Unpredictability in Human and Animal Amygdala , 2007, The Journal of Neuroscience.

[135]  J. Gläscher,et al.  Lesion mapping of cognitive control and value-based decision making in the prefrontal cortex , 2012, Proceedings of the National Academy of Sciences.

[136]  R. Nesse Why Has Natural Selection Left Us So Vulnerable to Anxiety and Mood Disorders? , 2011, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[137]  E. Phelps,et al.  Social learning of fear , 2007, Nature Neuroscience.

[138]  R. Dolan,et al.  Knowing how much you don't know: a neural organization of uncertainty estimates , 2012, Nature Reviews Neuroscience.

[139]  Olga V. Demler,et al.  Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. , 2005, Archives of general psychiatry.

[140]  Joseph E LeDoux,et al.  Preventing the return of fear in humans using reconsolidation update mechanisms , 2010, Nature.

[141]  D. Cicchetti Emotion and Adaptation , 1993 .

[142]  Joseph E LeDoux,et al.  Escape from fear: a detailed behavioral analysis of two atypical responses reinforced by CS termination. , 2007, Journal of experimental psychology. Animal behavior processes.

[143]  C. Don Looking for Spinoza: Joy, Sorrow, and the Feeling Brain , 2004 .

[144]  B. Mesquita,et al.  The experience of emotion. , 2007, Annual review of psychology.

[145]  K. Berridge,et al.  What is an unconscious emotion?(The case for unconscious "liking") , 2003, Cognition & emotion.

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

[147]  Michael S. Fanselow,et al.  A functional behavioristic approach to aversively motivated behavior: Predatory imminence as a determinant of the topography of defensive behavior. , 1988 .