Age-related differences in prefrontal control of heart rate in humans: a pharmacological blockade study.

The Neurovisceral Integration Model is based on the premise of significant central nervous system-peripheral nervous system interactions. In support of this model we have previously shown that the prefrontal cortex tonically inhibits cardioacceleratory circuits as evidenced by increased heart rate (HR) when the prefrontal cortex is inactivated by injections of sodium amobarbitol (ISA) into the internal carotid artery. In this report we re-examine these data to investigate possible age-related differences in the prefrontal control of HR in humans. Seventy-three patients were divided into three groups based on a tertile split with mean ages of 20, 34, and 47, respectively. There were significant age-related differences in cortical control of HR as evidenced by a significant three way interaction of age (young, middle, old) by side (left versus right) by time (baseline and epochs 1-10 of inactivation) [Roy's Root (10,59)=0.378, p=0.028]. Results showed significant HR increases that did not differ between hemispheres in the youngest age group, significant increases in the middle age group that were larger in the right hemisphere than in the left, and significant HR increases in the oldest group in the right hemisphere only. The findings suggest important age-related differences in cortical inhibitory control of HR that appear less lateralized in the youngest group and significantly attenuated in the oldest age group. These results have important implications for the understanding of age-related differences in cognitive, affective, behavioral, and physiological functioning. In addition they support the importance of investigating central nervous system-peripheral nervous system relationships.

[1]  Raymond J. Dolan,et al.  Anxiety Reduction through Detachment: Subjective, Physiological, and Neural Effects , 2005, Journal of Cognitive Neuroscience.

[2]  Paige E. Scalf,et al.  The implications of cortical recruitment and brain morphology for individual differences in inhibitory function in aging humans. , 2005, Psychology and aging.

[3]  R. J Dolan,et al.  Activity in ventromedial prefrontal cortex covaries with sympathetic skin conductance level: a physiological account of a “default mode” of brain function , 2004, NeuroImage.

[4]  M. O’Sullivan,et al.  Activate your online subscription , 2001, Neurology.

[5]  S Saha,et al.  ROLE OF THE CENTRAL NUCLEUS OF THE AMYGDALA IN THE CONTROL OF BLOOD PRESSURE: DESCENDING PATHWAYS TO MEDULLARY CARDIOVASCULAR NUCLEI , 2005, Clinical and experimental pharmacology & physiology.

[6]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[7]  Koji Jimura,et al.  Activation of Right Inferior Frontal Gyrus during Response Inhibition across Response Modalities , 2007, Journal of Cognitive Neuroscience.

[8]  Effects of normal aging on left ventricular lusitropic, inotropic, and chronotropic responses to dobutamine. , 2006, Journal of the American College of Cardiology.

[9]  N. Rempel-Clower,et al.  Role of Orbitofrontal Cortex Connections in Emotion , 2007, Annals of the New York Academy of Sciences.

[10]  Folkert Postema,et al.  Forebrain parasympathetic control of heart activity: retrograde transneuronal viral labeling in rats. , 1997, American journal of physiology. Heart and circulatory physiology.

[11]  Helen Barbas,et al.  The Prefrontal Cortex and Flexible Behavior , 2007, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[12]  J. Ojemann,et al.  The frontal lobe role in memory: a review of convergent evidence and implications for the Wada memory test , 2002, Epilepsy & Behavior.

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

[14]  Anthony A. Grace,et al.  Regulation of conditioned responses of basolateral amygdala neurons , 2002, Physiology & Behavior.

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

[16]  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.

[17]  E. Gordon,et al.  Regional White Matter and Neuropsychological Functioning across the Adult Lifespan , 2006, Biological Psychiatry.

[18]  J F Thayer,et al.  Neurological bases for balance-anxiety links. , 2001, Journal of anxiety disorders.

[19]  T. Batten,et al.  A GABAergic projection from the central nucleus of the amygdala to the nucleus of the solitary tract: a combined anterograde tracing and electron microscopic immunohistochemical study , 2000, Neuroscience.

[20]  D. Seo,et al.  Contralateral EEG Slowing and Amobarbital Distribution in Wada Test: An Intracarotid SPECT Study , 2000, Epilepsia.

[21]  R. Lane,et al.  A model of neurovisceral integration in emotion regulation and dysregulation. , 2000, Journal of affective disorders.

[22]  Alberto Radaelli,et al.  Invited review: aging and the cardiovascular system. , 2003, Journal of applied physiology.

[23]  Julian F. Thayer,et al.  21. Activity in medial prefrontal cortex correlates with vagal component of heart rate variability during emotion , 2001 .

[24]  A. Verberne,et al.  Cortical Modulation of theCardiovascular System , 1998, Progress in Neurobiology.

[25]  T. Opthof,et al.  The normal range and determinants of the intrinsic heart rate in man. , 2000, Cardiovascular research.

[26]  L. Resstel,et al.  Involvement of the medial prefrontal cortex in central cardiovascular modulation in the rat , 2006, Autonomic Neuroscience.

[27]  E. Stein,et al.  Right hemispheric dominance of inhibitory control: an event-related functional MRI study. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. N. Levy,et al.  Autonomic Interactions in Cardiac Control a , 1990, Annals of the New York Academy of Sciences.

[29]  J. Patterson,et al.  Regional cerebral perfusion and amytal distribution during the Wada test. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[30]  M. Weinand,et al.  Quantitative analysis of the EEG in the intracarotid amobarbital procedure. I. Amplitude analysis. , 1994, Electroencephalography and clinical neurophysiology.

[31]  B. J. Casey,et al.  Structural and functional brain development and its relation to cognitive development , 2000, Biological Psychology.

[32]  T. Robbins,et al.  Inhibition and the right inferior frontal cortex , 2004, Trends in Cognitive Sciences.

[33]  Adam P. Morris,et al.  Executive Brake Failure following Deactivation of Human Frontal Lobe , 2006 .

[34]  J. Thayer,et al.  Psychosomatics and psychopathology: looking up and down from the brain , 2005, Psychoneuroendocrinology.

[35]  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 .

[36]  Ulman Lindenberger,et al.  Delineating brain–behavior mappings across the lifespan: Substantive and methodological advances in developmental neuroscience , 2006, Neuroscience & Biobehavioral Reviews.

[37]  M. Weinand,et al.  Heart Rate and Heart Rate Variability Changes in the Intracarotid Sodium Amobarbital Test , 2001, Epilepsia.

[38]  A. D. Jose,et al.  The normal range and determinants of the intrinsic heart rate in man. , 1970, Cardiovascular research.

[39]  H. Barbas,et al.  Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression , 2003, BMC Neuroscience.

[40]  Y. Miyashita,et al.  Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI. , 1999, Brain : a journal of neurology.

[41]  K. Spyer,et al.  Annual review prize lecture. Central nervous mechanisms contributing to cardiovascular control. , 1994, The Journal of physiology.

[42]  Edith V. Sullivan,et al.  Frontal circuitry degradation marks healthy adult aging: Evidence from diffusion tensor imaging , 2005, NeuroImage.

[43]  Julian F. Thayer,et al.  Accentuated antagonism in the control of human heart rate , 2000, Clinical Autonomic Research.

[44]  S. Blakemore,et al.  Development of the adolescent brain: implications for executive function and social cognition. , 2006 .

[45]  H. Damasio,et al.  Neuroanatomical correlates of electrodermal skin conductance responses. , 1994, Psychophysiology.

[46]  Ravi S. Menon,et al.  Ventral medial prefrontal cortex and cardiovagal control in conscious humans , 2007, NeuroImage.

[47]  Phillip Anson Low,et al.  Clinical Autonomic Disorders , 1994 .

[48]  Julian F. Thayer,et al.  The importance of inhibition in dynamical systems models of emotion and neurobiology , 2005, Behavioral and Brain Sciences.

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

[50]  Cheryl L. Dahle,et al.  Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. , 2005, Cerebral cortex.

[51]  D. Rainnie,et al.  The Amygdala, Panic Disorder, and Cardiovascular Responses , 2003, Annals of the New York Academy of Sciences.

[52]  N. Bargalló,et al.  Can the Wada test evaluate mesial temporal function? , 2004, Neurology.

[53]  N. Liou,et al.  Horseradish peroxidase localization of sympathetic postganglionic and parasympathetic preganglionic neurons innervating the monkey heart. , 2004, The Chinese journal of physiology.

[54]  A. Damasio Descartes' error: emotion, reason, and the human brain. avon books , 1994 .

[55]  E. Benarroch The central autonomic network: functional organization, dysfunction, and perspective. , 1993, Mayo Clinic proceedings.