Manel J. Barbanoj

Low-resolution brain electromagnetic tomography revealed simultaneously active frontal and parietal sleep spindle sources in the human cortex.

Analyses of scalp-recorded sleep spindles have demonstrated topographically distinct slow and fast spindle waves. In the present paper, the electrical activity in the brain corresponding to different types of sleep spindles was estimated by means of low-resolution electromagnetic tomography. In its new implementation, this method is based on realistic head geometry and solution space is restricted to the cortical gray matter and hippocampus. In multichannel all-night electroencephalographic recordings, 10-20 artifact-free 1.25-s epochs with frontally, parietally and approximately equally distributed spindles were marked visually in 10 normal healthy subjects aged 20-35years. As a control condition, artifact-free non-spindle epochs 1-3s before or after the corresponding spindle episodes were marked. Low-resolution electromagnetic tomography demonstrated, independent of the scalp distribution, a distributed spindle source in the prefrontal cortex (Brodmann areas 9 and 10), oscillating with a frequency below 13Hz, and in the precuneus (Brodmann area 7), oscillating with a frequency above 13Hz. In extremely rare cases only the prefrontal or the parietal source was active. Brodmann areas 9 and 10 have principal connections to the dorsomedial thalamic nucleus; Brodmann area 7 is connected to the lateroposterior, laterodorsal and rostral intralaminar centrolateral thalamic nuclei. Thus, the localized cortical brain regions are directly connected with adjacent parts of the dorsal thalamus, where sleep spindles are generated. The results demonstrated simultaneously active cortical spindle sources which differed in frequency by approximately 2Hz and were located in brain regions known to be critically involved in the processing of sensory input, which is in line with the assumed functional role of sleep spindles.

Chronic effects of dopaminergic replacement on cognitive function in Parkinson's disease : A two-year follow-up study of previously untreated patients

The cognitive effects of dopaminergic treatment in Parkinsons disease (PD) are still controversial.

The SIESTA project polygraphic and clinical database

The SIESTA project had two major goals: developing new tools for analyzing computer-based sleep recordings and creating a reference database for sleep-related features. Basically, both goals have been reached, although validation and fine tuning of the sleep analyzer is still on-going. Investigations on the Web interface will be finished soon and a documentation of the database (including a CD-ROM with all test forms and all clinical, psychometric and actigraphic data as well as all R&K-scorings) will be published. Besides its scientific impact, the SIESTA project also emphasizes two other important aspects: the need of national and international cooperation between different experts and disciplines and the importance of standardized methods in scientific and clinical research.

A comparative study of automatic techniques for ocular artifact reduction in spontaneous EEG signals based on clinical target variables: A simulation case

Eye movement artifacts represent a critical issue for quantitative electroencephalography (EEG) analysis and a number of mathematical approaches have been proposed to reduce their contribution in EEG recordings. The aim of this paper was to objectively and quantitatively evaluate the performance of ocular filtering methods with respect to spectral target variables widely used in clinical and functional EEG studies. In particular the following methods were applied: regression analysis and some blind source separation (BSS) techniques based on second-order statistics (PCA, AMUSE and SOBI) and on higher-order statistics (JADE, INFOMAX and FASTICA). Considering blind source decomposition methods, a completely automatic procedure of BSS based on logical rules related to spectral and topographical information was proposed in order to identify the components related to ocular interference. The automatic procedure was applied in different montages of simulated EEG and electrooculography (EOG) recordings: a full montage with 19 EEG and 2 EOG channels, a reduced one with only 6 EEG leads and a third one where EOG channels were not available. Time and frequency results in all of them indicated that AMUSE and SOBI algorithms preserved and recovered more brain activity than the other methods mainly at anterior regions. In the case of full montage: (i) errors were lower than 5% for all spectral variables at anterior sites; and (ii) the highest improvement in the signal-to-artifact (SAR) ratio was obtained up to 40dB at these anterior sites. Finally, we concluded that second-order BSS-based algorithms (AMUSE and SOBI) provided an effective technique for eye movement removal even when EOG recordings were not available or when data length was short.

Artifact processing in topographic mapping of electroencephalographie activity in neuropsychopharmacology

Mapping of the electroencephalogram (EEG) has been found to be a valuable method in clinical neuropsychopharmacology. It is evident that careful treatment of artifacts is of utmost importance for EEG data processing, as artifacts that contaminate the EEG data can lead to spurious results. The artifact-processing method described in this article splits signal analysis into a preprocessing step, yielding individual electro-oculographic (EOG) regression factors for EOG minimization, and into a processing step, yielding target variables. The combination of avoiding, minimizing, and identifying artifacts, as well as visual checking of face validity, will help remove artifactual effects from the EEG.

Assessment of addiction severity among ritual users of ayahuasca

Ayahuasca is a psychoactive beverage used for magico-religious purposes in the Amazon. Recently, Brazilian syncretic churches have helped spread the ritual use of ayahuasca abroad. This trend has raised concerns that regular use of this N,N-dimethyltryptamine-containing tea may lead to the medical and psychosocial problems typically associated with drugs of abuse. Here we assess potential drug abuse-related problems in regular ayahuasca users. Addiction severity was assessed using the Addiction Severity Index (ASI), and history of alcohol and illicit drug use was recorded. In Study 1, jungle-based ayahuasca users (n=56) were compared vs. rural controls (n=56). In Study 2, urban-based ayahuasca users (n=71) were compared vs. urban controls (n=59). Follow-up studies were conducted 1 year later. In both studies, ayahuasca users showed significantly lower scores than controls on the ASI Alcohol Use, and Psychiatric Status subscales. The jungle-based ayahuasca users showed a significantly higher frequency of previous illicit drug use but this had ceased at the time of examination, except for cannabis. At follow-up, abstinence from illicit drug use was maintained in both groups except for cannabis in Study 1. However, differences on ASI scores were still significant in the jungle-based group but not in the urban group. Despite continuing ayahuasca use, a time-dependent worsening was only observed in one subscale (Family/Social relationships) in Study 2. Overall, the ritual use of ayahuasca, as assessed with the ASI in currently active users, does not appear to be associated with the deleterious psychosocial effects typically caused by other drugs of abuse.

Noradrenergic Stimulation Enhances Human Action Monitoring

Noradrenergic neurotransmission has been associated with the modulation of higher cognitive functions mediated by the prefrontal cortex. In the present study, the impact of noradrenergic stimulation on the human action-monitoring system, as indexed by event-related brain potentials, was examined. After the administration of a placebo or the selective α2-adrenoceptor antagonist yohimbine, which stimulates firing in the locus ceruleus and noradrenaline release, electroencephalograpic recordings were obtained from healthy volunteers performing a letter flanker task. Yohimbine led to an increase in the amplitude of the error-related negativity in conjunction with a significant reduction of action errors. Reaction times were unchanged, and the drug did not modify the N2 in congruent versus incongruent trials, a measure of preresponse conflict, or posterror adjustments as measured by posterror slowing of reaction time. The present findings suggest that the locus ceruleus-noradrenaline system exerts a rather specific effect on human action monitoring.

Personality, Psychopathology, Life Attitudes and Neuropsychological Performance among Ritual Users of Ayahuasca: A Longitudinal Study

Ayahuasca is an Amazonian psychoactive plant beverage containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting alkaloids (harmine, harmaline and tetrahydroharmine) that render it orally active. Ayahuasca ingestion is a central feature in several Brazilian syncretic churches that have expanded their activities to urban Brazil, Europe and North America. Members of these groups typically ingest ayahuasca at least twice per month. Prior research has shown that acute ayahuasca increases blood flow in prefrontal and temporal brain regions and that it elicits intense modifications in thought processes, perception and emotion. However, regular ayahuasca use does not seem to induce the pattern of addiction-related problems that characterize drugs of abuse. To study the impact of repeated ayahuasca use on general psychological well-being, mental health and cognition, here we assessed personality, psychopathology, life attitudes and neuropsychological performance in regular ayahuasca users (n = 127) and controls (n = 115) at baseline and 1 year later. Controls were actively participating in non-ayahuasca religions. Users showed higher Reward Dependence and Self-Transcendence and lower Harm Avoidance and Self-Directedness. They scored significantly lower on all psychopathology measures, showed better performance on the Stroop test, the Wisconsin Card Sorting Test and the Letter-Number Sequencing task from the WAIS-III, and better scores on the Frontal Systems Behavior Scale. Analysis of life attitudes showed higher scores on the Spiritual Orientation Inventory, the Purpose in Life Test and the Psychosocial Well-Being test. Despite the lower number of participants available at follow-up, overall differences with controls were maintained one year later. In conclusion, we found no evidence of psychological maladjustment, mental health deterioration or cognitive impairment in the ayahuasca-using group.

Effects of the South American Psychoactive Beverage Ayahuasca on Regional Brain Electrical Activity in Humans: A Functional Neuroimaging Study Using Low-Resolution Electromagnetic Tomography

Ayahuasca, a South American psychotropic plant tea obtained from Banisteriopsis caapi and Psychotria viridis, combines monoamine oxidase-inhibiting β-carboline alkaloids with N,N-dimethyltryptamine (DMT), a psychedelic agent showing 5-HT2A agonist activity. In a clinical research setting, ayahuasca has demonstrated a combined stimulatory and psychedelic effect profile, as measured by subjective effect self-assessment instruments and dose-dependent changes in spontaneous brain electrical activity, which parallel the time course of subjective effects. In the present study, the spatial distribution of ayahuasca-induced changes in brain electrical activity was investigated by means of low-resolution electromagnetic tomography (LORETA). Electroencephalography recordings were obtained from 18 volunteers after the administration of a dose of encapsulated freeze-dried ayahuasca containing 0.85 mg DMT/kg body weight and placebo. The intracerebral power density distribution was computed with LORETA from spectrally analyzed data, and subjective effects were measured by means of the Hallucinogen Rating Scale (HRS). Statistically significant differences compared to placebo were observed for LORETA power 60 and 90 min after dosing, together with increases in all six scales of the HRS. Ayahuasca decreased power density in the alpha-2, delta, theta and beta-1 frequency bands. Power decreases in the delta, alpha-2 and beta-1 bands were found predominantly over the temporo-parieto-occipital junction, whereas theta power was reduced in the temporomedial cortex and in frontomedial regions. The present results suggest the involvement of unimodal and heteromodal association cortex and limbic structures in the psychological effects elicited by ayahuasca.

Determination of N,N-dimethyltryptamine and β-carboline alkaloids in human plasma following oral administration of Ayahuasca

Ayahuasca is a South American psychotropic beverage prepared from plants native to the Amazon River Basin. It combines the hallucinogenic agent and 5-HT(2A/2C) agonist N,N-dimethyltryptamine (DMT) with beta-carboline alkaloids showing monoamine oxidase-inhibiting properties. In the present paper, an analytical methodology for the plasma quantification of the four main alkaloids present in ayahuasca plus two major metabolites is described. DMT was extracted by liquid-liquid extraction with n-pentane and quantified by gas chromatography with nitrogen-phosphorus detection. Recovery was 74%, and precision and accuracy were better than 9.9%. The limit of quantification (LOQ) was 1.6 ng/ml. Harmine, harmaline, and tetrahydroharmine (THH), the three main beta-carbolines present in ayahuasca, and harmol and harmalol (O-demethylation metabolites of harmine and harmaline, respectively) were measured in plasma by means of high-performance liquid chromatography (HPLC) with fluorescence detection. Sample preparation was accomplished by solid-phase extraction, which facilitated the automation of the process. All five beta-carbolines were measured using a single detector by switching wavelengths. Separation of harmol and harmalol required only slight changes in the chromatographic conditions. Method validation demonstrated good recoveries, above 87%, and accuracy and precision better than 13.4%. The LOQ was 0.5 ng/ml for harmine, 0.3 ng/ml for harmaline, 1.0 ng/ml for THH, and 0.3 ng/ml for harmol and harmalol. Good linearity was observed in the concentration ranges evaluated for DMT (2.5-50 ng/ml) and the beta-carbolines (0.3-100 ng/ml). The gas chromatography and HPLC methods described allowed adequate characterization of the pharmacokinetics of the four main alkaloids present in ayahuasca, and also of two major beta-carboline metabolites not previously described in the literature.