BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation

SummaryDirect vagus nerve stimulation (VNS) has proved to be an effective treatment for seizure disorder and major depression. However, since this invasive technique implies surgery, with its side-effects and relatively high financial costs, a non-invasive method to stimulate vagal afferences would be a great step forward. We studied effects of non-invasive electrical stimulation of the nerves in the left outer auditory canal in healthy subjects (n = 22), aiming to activate vagal afferences transcutaneously (t-VNS). Short-term changes in brain activation and subjective well-being induced by t-VNS were investigated by functional magnetic resonance imaging (fMRI) and psychometric assessment using the Adjective Mood Scale (AMS), a self-rating scale for current subjective feeling. Stimulation of the ear lobe served as a sham control.fMRI showed that robust t-VNS induced BOLD-signal decreases in limbic brain areas, including the amygdala, hippocampus, parahippocampal gyrus and the middle and superior temporal gyrus. Increased activation was seen in the insula, precentral gyrus and the thalamus. Psychometric assessment revealed significant improvement of well-being after t-VNS. Ear lobe stimulation as a sham control intervention did not show similar effects in either fMRI or psychometric assessment. No significant effects on heart rate, blood pressure or peripheral microcirculation could be detected during the stimulation procedure. Conclusions. Our study shows the feasibility and beneficial effects of transcutaneous nerve stimulation in the left auditory canal of healthy subjects. Brain activation patterns clearly share features with changes observed during invasive vagus nerve stimulation.

[1]  Jeffrey J Borckardt,et al.  Vagus nerve stimulation for the treatment of depression and other neuropsychiatric disorders , 2007, Expert review of neurotherapeutics.

[2]  S Thesen,et al.  Prospective acquisition correction for head motion with image‐based tracking for real‐time fMRI , 2000, Magnetic resonance in medicine.

[3]  M. Flowerdew,et al.  Transcutaneous electrical nerve stimulation and acupuncture-like transcutaneous electrical nerve stimulation for chronic low back pain. , 2006, The Cochrane database of systematic reviews.

[4]  D von Zerssen,et al.  [A scale for the objective evaluation of the state of subjective well-being as a method for longitudinal studies]. , 1970, Arzneimittel-Forschung.

[5]  D vonZerssen,et al.  [A scale for the objective evaluation of the state of subjective well-being as a method for longitudinal studies]. , 1970 .

[6]  H. Braus,et al.  Anatomie des Menschen: Ein Lehrbuch für Studierende und Ärzte Dritter Band Centrales Nervensystem , 1932 .

[7]  P. Butow,et al.  On the receiving end. IV: Validation of quality of life indicators. , 1991, Annals of oncology : official journal of the European Society for Medical Oncology.

[8]  J. Borckardt,et al.  Vagus nerve stimulation affects pain perception in depressed adults. , 2005, Pain research & management.

[9]  Steven Laureys,et al.  Posterior cingulate, precuneal and retrosplenial cortices: cytology and components of the neural network correlates of consciousness. , 2005, Progress in brain research.

[10]  Body temperature and mood variations during forced desynchronization in winter depression: a preliminary report , 2000, Biological Psychiatry.

[11]  J. Schoenen,et al.  Pain control by vagus nerve stimulation: from animal to man...and back. , 2005, Acta neurologica Belgica.

[12]  G. Królczyk,et al.  Influence of vagal nerve stimulation on food intake and body weight--results of experimental studies. , 2005, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[13]  F. Birklein,et al.  Vagus nerve stimulation suppresses pain but has limited effects on neurogenic inflammation in humans , 2006, European journal of pain.

[14]  P. Jerabek,et al.  Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response , 2000, Biological Psychiatry.

[15]  D. Hailey,et al.  Vagus nerve stimulation (VNS) for treatment-resistant depression. , 2001, Issues in emerging health technologies.

[16]  Paolo Maria Rossini,et al.  Motor cortex excitability in Alzheimer's disease: A transcranial magnetic stimulation study , 2003, Annals of neurology.

[17]  C. Epstein,et al.  Brain Blood‐flow Alterations Induced by Therapeutic Vagus Nerve Stimulation in Partial Epilepsy: II. Prolonged Effects at High and Low Levels of Stimulation , 2004, Epilepsia.

[18]  Effects of VNS on regional cerebral blood flow in depressed subjects , 2002, European Psychiatry.

[19]  V. Brown,et al.  Recordings from the rat locus coeruleus during acute vagal nerve stimulation in the anaesthetised rat , 2005, Neuroscience Letters.

[20]  D. Ross,et al.  Vagus nerve stimulation reduces daytime sleepiness in epilepsy patients , 2001, Neurology.

[21]  G. Parker,et al.  Cognitive generation of affect in bipolar depression: an fMRI study , 2004, The European journal of neuroscience.

[22]  Dean K. Naritoku,et al.  Enhanced recognition memory following vagus nerve stimulation in human subjects , 1999, Nature Neuroscience.

[23]  T A Yousry,et al.  Cranial neuroimaging and clinical neuroanatomy , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[24]  R. Watts,et al.  Cerebral Activation during Vagus Nerve Stimulation: A Functional MR Study , 2002, Epilepsia.

[25]  Wei Wang,et al.  Acupoint-specific fMRI patterns in human brain , 2005, Neuroscience Letters.

[26]  Thomas R. Henry,et al.  Therapeutic mechanisms of vagus nerve stimulation , 2002, Neurology.

[27]  G. Thickbroom,et al.  Repetitive paired-pulse TMS at I-wave periodicity markedly increases corticospinal excitability: A new technique for modulating synaptic plasticity , 2006, Clinical Neurophysiology.

[28]  M. Kalia,et al.  Brainstem projections of sensory and motor components of the vagus nerve in the rat , 1982, The Journal of comparative neurology.

[29]  R. Kuzniecky,et al.  Weight loss associated with vagus nerve stimulation , 2002, Neurology.

[30]  J. Zabara,et al.  The Implantable Neurocybernetic Prosthesis System , 1991, Pacing and clinical electrophysiology : PACE.

[31]  H. Handwerker,et al.  BOLD effects in different areas of the cerebral cortex during painful mechanical stimulation , 2003, Pain.

[32]  Y. Lapierre,et al.  Validity and sensitivity of the french version of the Zerssen BfS/BfS' self-rating mood scale during treatment with trazodone and amitriptyline. , 1981, Progress in neuro-psychopharmacology.

[33]  B. Biswal,et al.  fMRI in patients implanted with a vagal nerve stimulator , 2002, Seizure.

[34]  J. Lorberbaum,et al.  A review of functional neuroimaging studies of vagus nerve stimulation (VNS). , 2003, Journal of psychiatric research.

[35]  W. Kaschka,et al.  Increased limbic blood flow and total sleep deprivation in major depression with melancholia , 1994, Psychiatry Research: Neuroimaging.

[36]  Alan Frazer,et al.  VNS Therapy in Treatment-Resistant Depression: Clinical Evidence and Putative Neurobiological Mechanisms , 2006, Neuropsychopharmacology.

[37]  D. Woodbury,et al.  Effects of Vagal Stimulation on Experimentally Induced Seizures in Rats , 1990, Epilepsia.

[38]  A. Schmocker,et al.  [Self-rating of mood using a list of adjectives, Zersen's Befindlichkeits-Skala (BS)]. , 1975, L'Encephale.

[39]  David Aaron,et al.  A New Concept , 1974 .

[40]  T. Connor,et al.  The Effects of Vagus Nerve Stimulation on Pro- and Anti-Inflammatory Cytokines in Humans: A Preliminary Report , 2005, Neuroimmunomodulation.

[41]  Johannes Lang,et al.  Klinische anatomie des ohres , 1992 .

[42]  M. Honda,et al.  Expectation of Pain Enhances Responses to Nonpainful Somatosensory Stimulation in the Anterior Cingulate Cortex and Parietal Operculum/Posterior Insula: an Event-Related Functional Magnetic Resonance Imaging Study , 2000, The Journal of Neuroscience.

[43]  Jing Liu,et al.  Effects of electroacupuncture versus manual acupuncture on the human brain as measured by fMRI , 2005, Human brain mapping.

[44]  F. Strian,et al.  The time structure of depressive mood in schizophrenic patients , 1982, Acta psychiatrica Scandinavica.

[45]  T L Faber,et al.  Brain Blood Flow Alterations Induced by Therapeutic Vagus Nerve Stimulation in Partial Epilepsy: I. Acute Effects at High and Low Levels of Stimulation , 1998, Epilepsia.

[46]  D. Heeger,et al.  Linear Systems Analysis of Functional Magnetic Resonance Imaging in Human V1 , 1996, The Journal of Neuroscience.

[47]  E. G. Ventureyra,et al.  Transcutaneous vagus nerve stimulation for partial onset seizure therapy , 2000, Child's Nervous System.

[48]  M. Herrmann,et al.  Far field potentials from the brain stem after transcutaneous vagus nerve stimulation , 2003, Journal of Neural Transmission.

[49]  Fucang Jia,et al.  A pilot study of functional magnetic resonance imaging of the brain during manual and electroacupuncture stimulation of acupuncture point (LI-4 Hegu) in normal subjects reveals differential brain activation between methods. , 2002, Journal of alternative and complementary medicine.

[50]  D. Rousseau,et al.  On the Receiving End , 2006 .

[51]  J. Borckardt,et al.  Acute and Long-term VNS Effects on Pain Perception in a Case of Treatment-Resistant Depression , 2006, Neurocase.

[52]  P. O'Neil,et al.  Vagus nerve stimulation acutely alters food craving in adults with depression , 2007, Appetite.

[53]  B. Rosen,et al.  Acupuncture modulates the limbic system and subcortical gray structures of the human brain: Evidence from fMRI studies in normal subjects , 2000, Human brain mapping.

[54]  Steven C Schachter,et al.  Vagus nerve stimulation: where are we? , 2002, Current opinion in neurology.

[55]  S. Schachter.  Vagus nerve stimulation: mood and cognitive effects , 2004, Epilepsy & Behavior.

[56]  Cole A. Giller,et al.  Vagus Nerve Stimulation (VNS™) for Treatment-Resistant Depression: Efficacy, Side Effects, and Predictors of Outcome , 2001, Neuropsychopharmacology.

[57]  Friedrich Kopsch,et al.  Rauber/Kopsch Anatomie des Menschen : Lehrbuch und Atlas , 1987 .

[58]  Edward T. Bullmore,et al.  Task-induced deactivations during successful paired associates learning: An effect of age but not Alzheimer's disease , 2006, NeuroImage.

[59]  M. Tramèr,et al.  Transcutaneous electrical nerve stimulation (TENS) for chronic pain. , 2000, The Cochrane database of systematic reviews.

[60]  W. Maier,et al.  Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: An exploratory approach , 2005, Psychiatry Research: Neuroimaging.

[61]  Terri Gullickson.  Human Brain Anatomy in Computerized Images. , 1995 .

[62]  D. Zerssen.  Clinical Self-Rating Scales (CSRS) of the Munich Psychiatric Information System (PSYCHIS München) , 1986 .