High-frequency heart rate variability and cortico-striatal activity in men and women with social phobia

Identifying brain systems that regulate or modulate autonomic nervous system functions may identify pathways through which psychosocial factors can influence health and disease. Reduced high-frequency heart rate variability (HF-HRV) characterizes anxiety disordered patients and is predictive of adverse myocardial events. Sex differences in the prevalence of anxiety disorders and cardiac diseases implicate the possibility of sex specific neural regulation of HF-HRV. We investigated the correlation between HF-HRV and regional cerebral blood flow (rCBF) in 28 subjects (15 women) with social phobia undergoing a stressful public speaking task. Regional CBF was measured with [(15)O] water positron emission tomography. Stress induced rCBF correlated positively with HF-HRV in the right supra genual anterior cingulate cortex Brodmann's area (BA) 32, the right head of the caudate nucleus and bilaterally in the medial prefrontal cortex (BA10), extending into the dorsolateral prefrontal cortex (BA46) in the left hemisphere. Men showed larger positive co-variation in the caudate than women. These findings underscore the importance of the emotional division of the anterior cingulate cortex, the prefrontal cortex and the striatum in cardiovagal activity. The study replicates and extends results from published functional neuroimaging studies on cardioregulatory or modulatory areas in healthy subjects to men and women with social phobia. Moreover, caudate functions, possibly related to dopaminergic neurotransmission, have sexually dimorphic effects on vagal modulation of the heart.

[1]  J. Miller,et al.  Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. , 1987, The American journal of cardiology.

[2]  N. Frasure-smith,et al.  Depression and anxiety as predictors of 2-year cardiac events in patients with stable coronary artery disease. , 2008, Archives of general psychiatry.

[3]  A. Young,et al.  Neuropsychology of fear and loathing , 2001 .

[4]  Wayne Katon,et al.  Anxiety disorders and comorbid medical illness. , 2008, General hospital psychiatry.

[5]  Mats Fredrikson,et al.  Hypothalamic Blood Flow Correlates Positively With Stress-Induced Cortisol Levels in Subjects With Social Anxiety Disorder , 2006, Psychosomatic medicine.

[6]  Kewei Chen,et al.  Neural correlates of heart rate variability during emotion , 2009, NeuroImage.

[7]  T. Haney,et al.  Anxiety-proneness and coronary heart disease. , 1986, Journal of psychosomatic research.

[8]  M. Phillips,et al.  A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder , 2008, Molecular Psychiatry.

[9]  M. Liebowitz,et al.  Social phobia. , 2003, Collegium antropologicum.

[10]  G. Varigos,et al.  Sinus Arrhythmia in Acute Myocardial Infarction , 1978, The Medical journal of Australia.

[11]  A J Camm,et al.  Significance of long term components of heart rate variability for the further prognosis after acute myocardial infarction. , 1990, Cardiovascular research.

[12]  R. Davidson,et al.  Dysfunction in the neural circuitry of emotion regulation--a possible prelude to violence. , 2000, Science.

[13]  J. Flory,et al.  Trait Negative Affect: Toward an Integrated Model of Understanding Psychological Risk for Impairment in Cardiac Autonomic Function , 2008, Psychosomatic medicine.

[14]  J. Gross,et al.  Neural bases of social anxiety disorder: emotional reactivity and cognitive regulation during social and physical threat. , 2009, Archives of general psychiatry.

[15]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[16]  J. Saul,et al.  Beat-to-Beat Variations of Heart Rate Reflect Modulation of Cardiac Autonomic Outflow , 1990 .

[17]  M. Malik Heart Rate Variability , 1996, Clinical cardiology.

[18]  Martin P Paulus,et al.  Functional subdivisions within anterior cingulate cortex and their relationship to autonomic nervous system function , 2004, NeuroImage.

[19]  Dc Washington Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. , 1994 .

[20]  T. Hergueta,et al.  The mini international neuropsychiatric interview , 1998, European Psychiatry.

[21]  T. Furmark,et al.  Cerebral Blood Flow Changes After Treatment of Social Phobia with the Neurokinin-1 Antagonist GR205171, Citalopram, or Placebo , 2005, Biological Psychiatry.

[22]  A. Hamm,et al.  Individual differences in fear-potentiated startle as a function of resting heart rate variability: implications for panic disorder. , 2009, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[23]  Julian F. Thayer,et al.  The Non-invasive Assessment of Autonomic Influences on the Heart Using Impedance Cardiography and Heart Rate Variability , 2010 .

[24]  Mary-Frances O'Connor,et al.  Baseline Vagal Tone Predicts BOLD Response during Elicitation of Grief , 2007, Neuropsychopharmacology.

[25]  Jonathan Rottenberg,et al.  Cardiac vagal control in depression: A critical analysis , 2007, Biological Psychology.

[26]  R. Lane,et al.  Claude Bernard and the heart–brain connection: Further elaboration of a model of neurovisceral integration , 2009, Neuroscience & Biobehavioral Reviews.

[27]  Karl J. Friston,et al.  Psychophysiological and Modulatory Interactions in Neuroimaging , 1997, NeuroImage.

[28]  T. Furmark,et al.  A Link between Serotonin-Related Gene Polymorphisms, Amygdala Activity, and Placebo-Induced Relief from Social Anxiety , 2008, The Journal of Neuroscience.

[29]  Julian F. Thayer,et al.  Autonomic characteristics of generalized anxiety disorder and worry , 1996, Biological Psychiatry.

[30]  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 .

[31]  J L Lancaster,et al.  Automated Talairach Atlas labels for functional brain mapping , 2000, Human brain mapping.

[32]  Paul J. Laurienti,et al.  An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets , 2003, NeuroImage.

[33]  G. Breithardt,et al.  Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. , 1996 .

[34]  A. Malliani,et al.  Heart rate variability. Standards of measurement, physiological interpretation, and clinical use , 1996 .

[35]  C McRae,et al.  Myocardial infarction. , 2019, Australian family physician.

[36]  L. Luecken,et al.  Handbook of Physiological Research Methods in Health Psychology , 2007 .

[37]  Nan-Tsing Chiu,et al.  Correlation between striatal dopamine D2/D3 receptor binding and cardiovascular activity in healthy subjects. , 2006, American journal of hypertension.

[38]  A. Etkin,et al.  Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. , 2007, The American journal of psychiatry.

[39]  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.

[40]  J. Jennings,et al.  Regional cerebral blood flow correlates with heart period and high-frequency heart period variability during working-memory tasks: Implications for the cortical and subcortical regulation of cardiac autonomic activity. , 2004, Psychophysiology.

[41]  Mats Fredrikson,et al.  Serotonin transporter polymorphism related to amygdala excitability and symptom severity in patients with social phobia , 2004, Neuroscience Letters.

[42]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

[44]  T. Shallice,et al.  Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence. , 2003, Brain : a journal of neurology.

[45]  J. Rabe-Jabłońska,et al.  [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. , 1993, Psychiatria polska.

[46]  Lisa M Shin,et al.  Neuroimaging Studies of Amygdala Function in Anxiety Disorders , 2003, Annals of the New York Academy of Sciences.

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

[48]  Yoram Louzoun,et al.  Resting regional cerebral perfusion in recent posttraumatic stress disorder , 2003, Biological Psychiatry.

[49]  Stephan Eliez,et al.  Right anterior cingulate cortical volume covaries with respiratory sinus arrhythmia magnitude in combat veterans. , 2008, Journal of rehabilitation research and development.

[50]  Julian F. Thayer,et al.  The role of vagal function in the risk for cardiovascular disease and mortality , 2007, Biological Psychology.

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

[52]  Dean F. Wong,et al.  Sex Differences in Striatal Dopamine Release in Healthy Adults , 2006, Biological Psychiatry.

[53]  Bruce H. Friedman,et al.  An autonomic flexibility–neurovisceral integration model of anxiety and cardiac vagal tone , 2007, Biological Psychology.

[54]  Emery N. Brown,et al.  Brain correlates of autonomic modulation: Combining heart rate variability with fMRI , 2008, NeuroImage.

[55]  Ahmad R. Hariri,et al.  Human Choline Transporter Gene Variation Is Associated with Corticolimbic Reactivity and Autonomic-Cholinergic Function , 2006, Biological Psychiatry.

[56]  M. Partinen,et al.  Autonomic nervous system function in narcolepsy , 1994, Journal of sleep research.

[57]  George Howard,et al.  Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes , 2008, The Lancet Neurology.