Localization of MDMA‐induced brain activity in healthy volunteers using low resolution brain electromagnetic tomography (LORETA)

3,4‐Methylenedioxymethamphetamine (MDMA; 'Ecstasy') is a psychostimulant drug producing heightened mood and facilitated social communication. In animal studies, MDMA effects are primarily mediated by serotonin (5‐HT), but also by dopamine (DA) and possibly noradrenaline (NA). In humans, however, the neurochemical and neurophysiological basis of acute MDMA effects remains unknown. The distribution of active neuronal populations after administration of a single dose of MDMA (1.7 mg/kg) or placebo was studied in 16 healthy, MDMA‐naïve volunteers. Thirty‐one‐channel scalp EEGs during resting with open and closed eyes was analyzed in the different EEG frequency bands. Scalp maps of power showed significant, global differences between MDMA and placebo in both eye conditions and all frequency bands. Low resolution brain electromagnetic tomography (LORETA) was used to compute 3D, functional images of electric neuronal activity from the scalp EEG data. MDMA produced a widespread decrease of slow and medium frequency activity and an increase of fast frequency activity in the anterior temporal and posterior orbital cortex, concomitant with a marked enhancement of mood, emotional arousal and increased extraversion. This activation of frontotemporal areas indicates that the observed enhancement of mood and possibly the increased extroversion rely on modulation of limbic orbitofrontal and anterotemporal structures known to be involved in emotional processes. Comparison of the MDMA‐specific EEG pattern with that of various 5‐HT, DA, and NA agonists indicates that serotonin, noradrenaline, and, to a lesser degree, dopamine, contribute to the effects of MDMA on EEG, and possibly also on mood and behavior. Hum. Brain Mapping 14:152–165, 2001. © 2001 Wiley‐Liss, Inc.

[1]  R. Davidson,et al.  Anterior cingulate activity as a predictor of degree of treatment response in major depression: evidence from brain electrical tomography analysis. , 2001, The American journal of psychiatry.

[2]  D. Brillinger Time series - data analysis and theory , 1981, Classics in applied mathematics.

[3]  Mark D'Esposito,et al.  Cognitive Association Formation in Human Memory Revealed by Spatiotemporal Brain Imaging , 2001, Neuron.

[4]  Roberto D. Pascual-Marqui,et al.  Effect of the 5-HT1A partial agonist buspirone on regional brain electrical activity in man: a functional neuroimaging study using low-resolution electromagnetic tomography (LORETA) , 2000, Psychiatry Research: Neuroimaging.

[5]  F. Vollenweider,et al.  Acute Psychological Effects of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) are Attenuated by the Serotonin Uptake Inhibitor Citalopram , 1999, Neuropsychopharmacology.

[6]  D Lehmann,et al.  Mood state and brain electric activity in Ecstasy users , 2000, Neuroreport.

[7]  T. Koenig,et al.  Low resolution brain electromagnetic tomography (LORETA) functional imaging in acute, neuroleptic-naive, first-episode, productive schizophrenia , 1999, Psychiatry Research: Neuroimaging.

[8]  T. Inouye,et al.  Medial prefrontal cortex generates frontal midline theta rhythm. , 1999, Neuroreport.

[9]  R. Pascual-Marqui Review of methods for solving the EEG inverse problem , 1999 .

[10]  E. Gouzoulis-Mayfrank,et al.  Hallucinogenic drug induced states resemble acute endogenous psychoses: results of an empirical study , 1998, European Psychiatry.

[11]  F. Vollenweider,et al.  Psychological and Cardiovascular Effects and Short-Term Sequelae of MDMA (“Ecstasy”) in MDMA-Naïve Healthy Volunteers , 1998, Neuropsychopharmacology.

[12]  F. Vollenweider Advances and Pathophysiological Models of Hallucinogenic Drug Actions in Humans: A Preamble to Schizophrenia Research , 1998, Pharmacopsychiatry.

[13]  A Dittrich,et al.  The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans , 1998, Pharmacopsychiatry.

[14]  E. Gouzoulis-Mayfrank,et al.  Methodological issues of human experimental research with hallucinogens. , 1998, Pharmacopsychiatry.

[15]  T Landis,et al.  Non-invasive epileptic focus localization using EEG-triggered functional MRI and electromagnetic tomography. , 1998, Electroencephalography and clinical neurophysiology.

[16]  R D Pascual-Marqui,et al.  Differential effects of normal aging on sources of standard N1, target N1 and target P300 auditory event-related brain potentials revealed by low resolution electromagnetic tomography (LORETA). , 1998, Electroencephalography and clinical neurophysiology.

[17]  G A Miller,et al.  Patterns of regional brain activity differentiate types of anxiety. , 1997, Journal of abnormal psychology.

[18]  E. Niedermeyer Alpha rhythms as physiological and abnormal phenomena. , 1997, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[19]  J D Watson,et al.  Nonparametric Analysis of Statistic Images from Functional Mapping Experiments , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[20]  J. Deakin,et al.  5 -HT, antidepressant drugs and the psychosocial origins of depression , 1996, Journal of psychopharmacology.

[21]  L. Brothers,et al.  Brain mechanisms of social cognition. , 1996, Journal of psychopharmacology.

[22]  V. Kiroy,et al.  EEG after prolonged mental activity. , 1996, The International journal of neuroscience.

[23]  J. Mendelson,et al.  Electroencephalographic correlates of marihuana-induced euphoria. , 1995, Drug and alcohol dependence.

[24]  A. Bond,et al.  The effects of D-fenfluramine on mood and performance, and on neuroendocrine indicators of 5-HT function , 1995, Journal of psychopharmacology.

[25]  D. Lehmann,et al.  Low resolution electromagnetic tomography: a new method for localizing electrical activity in the brain. , 1994, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[26]  Fluoxetine effects on cerebral glucose metabolism. , 1994, Neuroreport.

[27]  P. Anderer,et al.  Clinical-pharmacological study with the two isomers (d-, l-) of fenfluramine and its comparison with chlorpromazine and d-amphetamine: blood levels, EEG mapping and safety evaluation. , 1993, Methods and findings in experimental and clinical pharmacology.

[28]  K. K. Tan,et al.  The spatial location of EEG electrodes: locating the best-fitting sphere relative to cortical anatomy. , 1993, Electroencephalography and clinical neurophysiology.

[29]  W. Hall,et al.  Recreational MDMA use in Sydney: a profile of 'Ecstacy' users and their experiences with the drug. , 1992, British journal of addiction.

[30]  E. Fetz,et al.  Coherent 25- to 35-Hz oscillations in the sensorimotor cortex of awake behaving monkeys. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Y. Mizuki,et al.  Differential responses to mental stress in high and low anxious normal humans assessed by frontal midline theta activity. , 1992, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[32]  B. Connors,et al.  Intrinsic oscillations of neocortex generated by layer 5 pyramidal neurons. , 1991, Science.

[33]  Joseph E. LeDoux,et al.  Emotion and the limbic system concept , 1991 .

[34]  M M Mesulam,et al.  Large‐scale neurocognitive networks and distributed processing for attention, language, and memory , 1990, Annals of neurology.

[35]  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 .

[36]  J. Mendelson,et al.  Behavioral and EEG studies of acute cocaine administration: comparisons with morphine, amphetamine, pentobarbital, nicotine, ethanol and marijuana. , 1989, NIDA research monograph.

[37]  E. D. De Souza,et al.  Pharmacologic profile of MDMA (3,4-methylenedioxymethamphetamine) at various brain recognition sites. , 1988, European journal of pharmacology.

[38]  B. Yamamoto,et al.  The acute effects of methylenedioxymethamphetamine on dopamine release in the awake-behaving rat. , 1988, European journal of pharmacology.

[39]  J. Bouyer,et al.  Anatomical localization of cortical beta rhythms in cat , 1987, Neuroscience.

[40]  G. Greer,et al.  Subjective reports of the effects of MDMA in a clinical setting. , 1986, Journal of psychoactive drugs.

[41]  R. E. Schultes Halluzinogene — psychische grenzzustande in forschung und psychotherapie: Hanscarl Leuner, Verlag Hans Huber, Bern, 1981, 458 pp., 33 figs., tables 5 (DM48.00, approx. US$22.00) , 1984 .

[42]  D. Sheer,et al.  Focused Arousal, 40-Hz EEG, and Dysfunction , 1984 .

[43]  P. Buser,et al.  Patterns of Activities in the Ventrobasal Thalamus and Somatic Cortex SI During Behavioral Immobility in the Awake Cat: Focal Waking Rhythms , 1983 .

[44]  B. Saletu Pharmaco-EEG profiles of typical and atypical antidepressants. , 1982, Advances in biochemical psychopharmacology.

[45]  W M Herrmann,et al.  Reflections on the topics: EEG frequency bands and regulation of vigilance. , 1979, Pharmakopsychiatrie, Neuro-Psychopharmakologie.

[46]  F. H. Lopes da Silva,et al.  Dynamic characteristics of visual evoked potentials in the dog. II. Beta frequency selectivity in evoked potentials and background activity. , 1970, Electroencephalography and clinical neurophysiology.