Brain structure correlates of individual differences in the acquisition and inhibition of conditioned fear.

Research employing aversive conditioning paradigms has elucidated the neurocircuitry involved in acquiring and diminishing fear responses. However, the factors underlying individual differences in fear acquisition and inhibition are not presently well understood. In this study, we explored whether the magnitude of individuals' acquired fear responses and the modulation of these responses via 2 fear reduction methods were correlated with structural differences in brain regions involved in affective processing. Physiological and structural magnetic resonance imaging data were obtained from experiments exploring extinction retention and intentional cognitive regulation. Our results identified 2 regions in which individual variation in brain structure correlated with subjects' fear-related arousal. Confirming previous results, increased thickness in ventromedial prefrontal cortex was correlated with the degree of extinction retention. Additionally, subjects with greater thickness in the posterior insula exhibited larger conditioned responses during acquisition. The data suggest a trend toward a negative correlation between amygdala volume and fear acquisition magnitude. There was no significant correlation between fear reduction via cognitive regulation and thickness in our prefrontal regions of interest. Acquisition and regulation measures were uncorrelated, suggesting that while certain individuals may have a propensity toward increased expression of conditioned fear, these responses can be diminished via both extinction and cognitive regulation.

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

[2]  A M Dale,et al.  Measuring the thickness of the human cerebral cortex from magnetic resonance images. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Joseph E LeDoux,et al.  Brain Mechanisms of Fear Extinction: Historical Perspectives on the Contribution of Prefrontal Cortex , 2006, Biological Psychiatry.

[4]  Joseph E LeDoux Emotion Circuits in the Brain , 2000 .

[5]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[6]  Anthony K. P. Jones,et al.  Modulation of pain ratings by expectation and uncertainty: Behavioral characteristics and anticipatory neural correlates , 2008, PAIN.

[7]  J. Mugler,et al.  Three‐dimensional magnetization‐prepared rapid gradient‐echo imaging (3D MP RAGE) , 1990, Magnetic resonance in medicine.

[8]  A. I. Silver,et al.  The effect of UCS intensity in classical and avoidance GSR conditioning , 1969, Conditional reflex.

[9]  Yuchiao Chang,et al.  Presence and acquired origin of reduced recall for fear extinction in PTSD: results of a twin study. , 2008, Journal of psychiatric research.

[10]  Peter Dayan,et al.  A Neural Substrate of Prediction and Reward , 1997, Science.

[11]  Joseph E LeDoux,et al.  Contributions of the Amygdala to Emotion Processing: From Animal Models to Human Behavior , 2005, Neuron.

[12]  G. McCarthy,et al.  Decisions under Uncertainty: Probabilistic Context Influences Activation of Prefrontal and Parietal Cortices , 2005, The Journal of Neuroscience.

[13]  D. S. Zahm,et al.  Specificity in the Projections of Prefrontal and Insular Cortex to Ventral Striatopallidum and the Extended Amygdala , 2005, The Journal of Neuroscience.

[14]  Catherine A Hartley,et al.  Changing Fear: The Neurocircuitry of Emotion Regulation , 2010, Neuropsychopharmacology.

[15]  H. Schlosberg,et al.  A simple test of the normality of twenty-four distributions of electrical skin conductance. , 1953, Science.

[16]  M. Bouton Context and behavioral processes in extinction. , 2004, Learning & memory.

[17]  William D S Killgore,et al.  Reduced Amygdala Volumes in First-Episode Bipolar Disorder and Correlation with Cerebral White Matter , 2007, Biological Psychiatry.

[18]  Brent L. Hughes,et al.  Prefrontal-Subcortical Pathways Mediating Successful Emotion Regulation , 2008, Neuron.

[19]  H. Burton,et al.  Somatic submodality distribution within the second somatosensory (SII), 7b, retroinsular, postauditory, and granular insular cortical areas of M. fascicularis , 1980, The Journal of comparative neurology.

[20]  M. Fendt,et al.  The neuroanatomical and neurochemical basis of conditioned fear , 1999, Neuroscience & Biobehavioral Reviews.

[21]  S. Rauch,et al.  Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. , 2006, Learning & memory.

[22]  Bruce Fischl,et al.  Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J. Girvin,et al.  Cardiovascular effects of human insular cortex stimulation , 1992, Neurology.

[24]  J. Gross,et al.  The cognitive control of emotion , 2005, Trends in Cognitive Sciences.

[25]  H. Critchley Electrodermal responses: what happens in the brain. , 2002, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[26]  Ahmad R. Hariri,et al.  Individual Differences in Stressor-Evoked Blood Pressure Reactivity Vary with Activation, Volume, and Functional Connectivity of the Amygdala , 2008, The Journal of Neuroscience.

[27]  Marianna D. Eddy,et al.  Regionally localized thinning of the cerebral cortex in schizophrenia , 2003, Schizophrenia Research.

[28]  G. Quirk,et al.  Neural Mechanisms of Extinction Learning and Retrieval , 2008, Neuropsychopharmacology.

[29]  A. Dale,et al.  Regional and progressive thinning of the cortical ribbon in Huntington’s disease , 2002, Neurology.

[30]  André J. W. van der Kouwe,et al.  Detection of cortical thickness correlates of cognitive performance: Reliability across MRI scan sessions, scanners, and field strengths , 2008, NeuroImage.

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

[32]  Y. Ninomiya,et al.  Leptin as a modulator of sweet taste sensitivities in mice. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[33]  J. Gore,et al.  Activation of the left amygdala to a cognitive representation of fear , 2001, Nature Neuroscience.

[34]  Anders M. Dale,et al.  Automated manifold surgery: constructing geometrically accurate and topologically correct models of the human cerebral cortex , 2001, IEEE Transactions on Medical Imaging.

[35]  S. Kapur,et al.  Direct Activation of the Ventral Striatum in Anticipation of Aversive Stimuli , 2003, Neuron.

[36]  P. Rakic A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution , 1995, Trends in Neurosciences.

[37]  Anders M. Dale,et al.  Cortical Surface-Based Analysis I. Segmentation and Surface Reconstruction , 1999, NeuroImage.

[38]  H. Critchley Review: Electrodermal Responses: What Happens in the Brain , 2002 .

[39]  R. Peyron,et al.  Functional imaging of brain responses to pain. A review and meta-analysis (2000) , 2000, Neurophysiologie Clinique/Clinical Neurophysiology.

[40]  Richard J. Davidson,et al.  Neural-Cardiac Coupling in Threat-Evoked Anxiety , 2005, Journal of Cognitive Neuroscience.

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

[42]  H. Barbas Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices , 2000, Brain Research Bulletin.

[43]  Nestor Schmajuk,et al.  Interpreting patterns of brain activation in human fear conditioning with an attentional-associative learning model. , 2009, Behavioral neuroscience.

[44]  Jasper A. J. Smits,et al.  Extinction retention predicts improvement in social anxiety symptoms following exposure therapy , 2009, Depression and anxiety.

[45]  Kevin N. Ochsner,et al.  For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion , 2004, NeuroImage.

[46]  H. Critchley,et al.  Neural Activity Relating to Generation and Representation of Galvanic Skin Conductance Responses: A Functional Magnetic Resonance Imaging Study , 2000, The Journal of Neuroscience.

[47]  Murray B. Stein,et al.  Anticipation of Aversive Visual Stimuli Is Associated With Increased Insula Activation in Anxiety-Prone Subjects , 2006, Biological Psychiatry.

[48]  Anders M. Dale,et al.  Improved Localization of Cortical Activity By Combining EEG and MEG with MRI Cortical Surface Reconstruction , 2002 .

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

[50]  Joseph E LeDoux,et al.  Neural Circuitry Underlying the Regulation of Conditioned Fear and Its Relation to Extinction , 2008, Neuron.

[51]  Robert W. Williams,et al.  Variation in Mouse Basolateral Amygdala Volume is Associated With Differences in Stress Reactivity and Fear Learning , 2008, Neuropsychopharmacology.

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

[53]  KJ Worsley,et al.  SurfStat: A Matlab toolbox for the statistical analysis of univariate and multivariate surface and volumetric data using linear mixed effects models and random field theory , 2009, NeuroImage.

[54]  G. Quirk,et al.  Neurons in medial prefrontal cortex signal memory for fear extinction , 2002, Nature.

[55]  R. Rescorla,et al.  A theory of Pavlovian conditioning : Variations in the effectiveness of reinforcement and nonreinforcement , 1972 .

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

[57]  Daniel L Adams,et al.  The cortical column: a structure without a function , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[58]  Heather L. Urry,et al.  Amygdala and Ventromedial Prefrontal Cortex Are Inversely Coupled during Regulation of Negative Affect and Predict the Diurnal Pattern of Cortisol Secretion among Older Adults , 2006, The Journal of Neuroscience.

[59]  Michael Davis,et al.  Pain Pathways Involved in Fear Conditioning Measured with Fear-Potentiated Startle: Lesion Studies , 1999, The Journal of Neuroscience.

[60]  F. Mauguière,et al.  Representation of pain and somatic sensation in the human insula: a study of responses to direct electrical cortical stimulation. , 2002, Cerebral cortex.

[61]  V. Mountcastle The columnar organization of the neocortex. , 1997, Brain : a journal of neurology.

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

[63]  A. Dale,et al.  Cortical Surface-Based Analysis II: Inflation, Flattening, and a Surface-Based Coordinate System , 1999, NeuroImage.

[64]  M. Beauregard,et al.  Neural Correlates of Conscious Self-Regulation of Emotion , 2001, The Journal of Neuroscience.

[65]  Issidoros C. Sarinopoulos,et al.  Uncertainty during anticipation modulates neural responses to aversion in human insula and amygdala. , 2010, Cerebral cortex.

[66]  Nikos Makris,et al.  Automatically parcellating the human cerebral cortex. , 2004, Cerebral cortex.

[67]  Ceri H. Davies,et al.  Loss of Hippocampal Serine Protease BSP1/Neuropsin Predisposes to Global Seizure Activity , 2001, The Journal of Neuroscience.

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

[69]  Lisa M. Shin,et al.  Neurocircuitry Models of Posttraumatic Stress Disorder and Extinction: Human Neuroimaging Research—Past, Present, and Future , 2006, Biological Psychiatry.

[70]  Hans-Jürgen Möller,et al.  Amygdala Volume and Depressive Symptoms in Patients With Borderline Personality Disorder , 2006, Biological Psychiatry.

[71]  Joseph E LeDoux,et al.  Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats. , 1995, Behavioral neuroscience.

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

[73]  Elliot A. Stein,et al.  Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning , 2007 .

[74]  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 .

[75]  Edward E. Smith,et al.  Placebo-Induced Changes in fMRI in the Anticipation and Experience of Pain , 2004, Science.

[76]  A. I. Silver,et al.  Effects of UCS intensity and postpeak acquisition trials on classical conditioning of the SCR. , 1978, Acta psychologica.

[77]  Joseph E LeDoux,et al.  Individual differences in fear: isolating fear reactivity and fear recovery phenotypes. , 2007, Journal of traumatic stress.

[78]  H. Critchley,et al.  Fear Conditioning in Humans The Influence of Awareness and Autonomic Arousal on Functional Neuroanatomy , 2002, Neuron.

[79]  Peter A Bandettini,et al.  Impact of continuous versus intermittent CS-UCS pairing on human brain activation during Pavlovian fear conditioning. , 2007, Behavioral neuroscience.

[80]  Stephen Maren Neurobiology of Pavlovian fear conditioning. , 2001, Annual review of neuroscience.