The Effect of Clonidine Infusion on Distribution of Regional Cerebral Blood Flow in Volunteers

BACKGROUND: Through their action on the locus coeruleus, &agr;2-adrenoceptor agonists induce rapidly reversible sedation while partially preserving cognitive brain functions. Our goal in this observational study was to map brain regions whose activity is modified by clonidine infusion so as to better understand its loci of action, especially in relation to sedation. METHODS: Six ASA I–II right-handed volunteers were recruited. Electroencephalogram (EEG) was monitored continuously. After a baseline H215O activation scan, clonidine infusion was started at a rate ranging from 6 to 10 &mgr;g · kg−1 · h−1. A sequence of 11 similar scans was then performed at 8 min intervals. Plasma clonidine concentration was measured. Using statistical parametric mapping, we sought linear correlations between normalized regional cerebral blood flow (rCBF), an indicator of regional brain activity, and plasma clonidine concentration or spindle EEG activity. RESULTS: Clonidine induced clinical sedation and EEG patterns (spindles) comparable to early stage nonrapid eye movement sleep. A significant negative linear correlation between clonidine concentration and rCBF or spindle activity was observed in the thalamus, prefrontal, orbital and parietal association cortex, posterior cingulate cortex, and precuneus. CONCLUSIONS: The EEG patterns and decreases in rCBF of specific brain regions observed during clonidine-induced sedation are similar to those of early stage nonrapid eye movement sleep. Patterns of deactivated brain regions are also comparable to those observed during general anesthesia or vegetative state, reinforcing the hypothesis that alterations in the activity of a common network occur during these modified conscious states.

[1]  Scott T. Grafton,et al.  Wandering Minds: The Default Network and Stimulus-Independent Thought , 2007, Science.

[2]  J. Takala,et al.  The Effects of Dexmedetomidine/Remifentanil and Midazolam/Remifentanil on Auditory-Evoked Potentials and Electroencephalogram at Light-to-Moderate Sedation Levels in Healthy Subjects , 2006, Anesthesia and analgesia.

[3]  R. Zatorre,et al.  Cortical Processing of Complex Auditory Stimuli during Alterations of Consciousness with the General Anesthetic Propofol , 2006, Anesthesiology.

[4]  W. Kox,et al.  Presence of 14Hz spindle oscillations in the human EEG during deep anesthesia , 2006, Clinical Neurophysiology.

[5]  Michael D. Rugg,et al.  Content-specificity of the neural correlates of recollection , 2005, Neuropsychologia.

[6]  Karen M. Jones,et al.  Phonological decoding involves left posterior fusiform gyrus , 2005, Human brain mapping.

[7]  Masatoshi Itoh,et al.  Recruitment of fusiform face area associated with listening to degraded speech sounds in auditory–visual speech perception: a PET study , 2005, Neuroscience Letters.

[8]  Peter Erhard,et al.  A common neural basis for receptive and expressive communication of pleasant facial affect , 2005, NeuroImage.

[9]  M. Mesulam,et al.  Shifts of Effective Connectivity within a Language Network during Rhyming and Spelling , 2005, The Journal of Neuroscience.

[10]  M. Steriade.  Sleep, epilepsy and thalamic reticular inhibitory neurons , 2005, Trends in Neurosciences.

[11]  P. Fox,et al.  Neuroanatomical correlates of phonological processing of Chinese characters and alphabetic words: A meta‐analysis , 2005, Human brain mapping.

[12]  Steven Laureys,et al.  AM: The vegetative state , 2022 .

[13]  Bradley Beattie,et al.  Propofol and Thiopental Do Not Interfere with Regional Cerebral Blood Flow Response at Sedative Concentrations , 2005, Anesthesiology.

[14]  Jennifer T Coull,et al.  Attentional effects of noradrenaline vary with arousal level: selective activation of thalamic pulvinar in humans , 2004, NeuroImage.

[15]  T. Schwartz,et al.  Dexmedetomidine and Neurocognitive Testing in Awake Craniotomy , 2004, Journal of neurosurgical anesthesiology.

[16]  Hugo Vereecke,et al.  Ability of the Bispectral Index, Autoregressive Modelling with Exogenous Input-derived Auditory Evoked Potentials, and Predicted Propofol Concentrations to Measure Patient Responsiveness during Anesthesia with Propofol and Remifentanil , 2003, Anesthesiology.

[17]  S. Aalto,et al.  Effects of Sevoflurane, Propofol, and Adjunct Nitrous Oxide on Regional Cerebral Blood Flow, Oxygen Consumption, and Blood Volume in Humans , 2003, Anesthesiology.

[18]  Nathan S White,et al.  Impaired thalamocortical connectivity in humans during general-anesthetic-induced unconsciousness , 2003, NeuroImage.

[19]  Michael J Brammer,et al.  Engagement of brain areas implicated in processing inner speech in people with auditory hallucinations. , 2003, The British journal of psychiatry : the journal of mental science.

[20]  Jun Lu,et al.  The &agr;2-Adrenoceptor Agonist Dexmedetomidine Converges on an Endogenous Sleep-promoting Pathway to Exert Its Sedative Effects , 2003, Anesthesiology.

[21]  T. Guo,et al.  The sedative component of anesthesia is mediated by GABAA receptors in an endogenous sleep pathway , 2002, Nature Neuroscience.

[22]  Leanne Groban,et al.  Dexmedetomidine-Induced Sedation in Volunteers Decreases Regional and Global Cerebral Blood Flow , 2002, Anesthesia and analgesia.

[23]  T. Ebert,et al.  The Efficacy, Side Effects, and Recovery Characteristics of Dexmedetomidine Versus Propofol When Used for Intraoperative Sedation , 2002, Anesthesia and analgesia.

[24]  Naidong Weng,et al.  DEVELOPMENT AND VALIDATION OF A LIQUID CHROMATOGRAPHY–TANDEM MASS SPECTROMETRY METHOD, USING SILICA COLUMN AND AQUEOUS-ORGANIC MOBILE PHASE, FOR THE ANALYSIS OF CLONIDINE AS LOW AS 10 pg/mL IN HUMAN SERUM , 2002 .

[25]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[26]  S. Houle,et al.  Noradrenergic dysfunction in the prefrontal cortex in depression: an [15O] H2O PET study of the neuromodulatory effects of clonidine , 2001, Biological Psychiatry.

[27]  J. H. Fallon,et al.  Toward a Unified Theory of Narcosis: Brain Imaging Evidence for a Thalamocortical Switch as the Neurophysiologic Basis of Anesthetic-Induced Unconsciousness , 2000, Consciousness and Cognition.

[28]  Maquet,et al.  Functional neuroimaging of normal human sleep by positron emission tomography , 2000, Journal of sleep research.

[29]  Richard S. J. Frackowiak,et al.  Representation of the temporal envelope of sounds in the human brain. , 2000, Journal of neurophysiology.

[30]  B. Bromm,et al.  Topography of Clonidine-induced Electroencephalographic Changes Evaluated by Principal Component Analysis , 2000, Anesthesiology.

[31]  Judith E. Hall,et al.  Sedative, Amnestic, and Analgesic Properties of Small-Dose Dexmedetomidine Infusions , 2000, Anesthesia and analgesia.

[32]  C. Doré,et al.  Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 2: Auditory and somatosensory evoked responses. , 1999, British journal of anaesthesia.

[33]  R. M. Jones,et al.  Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 1: Pharmacodynamic and pharmacokinetic interactions. , 1999, British journal of anaesthesia.

[34]  Alan C. Evans,et al.  Brain Mechanisms of Propofol-Induced Loss of Consciousness in Humans: a Positron Emission Tomographic Study , 1999, The Journal of Neuroscience.

[35]  S Laureys,et al.  Cerebral metabolism during vegetative state and after recovery to consciousness , 1999, Journal of neurology, neurosurgery, and psychiatry.

[36]  C. Phillips,et al.  Impaired Effective Cortical Connectivity in Vegetative State: Preliminary Investigation Using PET , 1999, NeuroImage.

[37]  R. Haier,et al.  Functional brain imaging during anesthesia in humans: effects of halothane on global and regional cerebral glucose metabolism. , 1999, Anesthesiology.

[38]  S. Larson,et al.  Midazolam Changes Cerebral Blood Flow in Discrete Brain Regions: An H2‐15O Positron Emission Tomography Study , 1997, Anesthesiology.

[39]  P. Talke,et al.  The Effect of Clonidine on Cerebral Blood Flow Velocity, Carbon Dioxide Cerebral Vasoreactivity, and Response to Increased Arterial Pressure in Human Volunteers , 1997, Anesthesiology.

[40]  J. Pernier,et al.  Stimulus Specificity of Phase-Locked and Non-Phase-Locked 40 Hz Visual Responses in Human , 1996, The Journal of Neuroscience.

[41]  S. Henneberg,et al.  Autoregressive Modeling with Exogenous Input of Middle-Latency Auditory-Evoked Potentials to Measure Rapid Changes in Depth of Anesthesia , 1996, Methods of Information in Medicine.

[42]  E. Niedermeyer.  Consciousness: Function and Definition , 1994, Clinical EEG.

[43]  G. Buzsáki.  The thalamic clock: Emergent network properties , 1991, Neuroscience.

[44]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[45]  Richard Kronland-Martinet,et al.  Analysis of Sound Patterns through Wavelet transforms , 1987, Int. J. Pattern Recognit. Artif. Intell..

[46]  F. Bavoux,et al.  [Hallucinatory syndromes regressing after withdrawal of clonidine]. , 1984, Therapie.

[47]  P. Edlund,et al.  Pharmacokinetics of clonidine and its relation to the hypotensive effect in patients. , 1978, British journal of clinical pharmacology.

[48]  Lukas Scheef,et al.  Mediotemporal contributions to semantic processing: fMRI evidence from ambiguity processing during semantic context verification , 2005, Hippocampus.

[49]  Judith E. Hall,et al.  Sedative, analgesic and cognitive effects of clonidine infusions in humans. , 2001, British journal of anaesthesia.

[50]  G. Di Giacomo,et al.  [Clonidine hallucinations: description of a clinical case]. , 2000, La Clinica terapeutica.

[51]  M. Rendell,et al.  Clonidine hallucinations. , 1980, Annals of internal medicine.