Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis

RATIONALE: Many studies have reported deficits of mismatch negativity (MMN) in schizophrenic patients. Pharmacological challenges with hallucinogens in healthy humans are used as models for psychotic states. Previous studies reported a significant reduction of MMN after ketamine (N-methyl-D-aspartate acid [NMDA] antagonist model) but not after psilocybin (5HT2A agonist model). OBJECTIVES: The aim of the present study was to directly compare the two models of psychosis using an intraindividual crossover design. MATERIALS AND METHODS: Fifteen healthy subjects participated in a randomized, double-blind, crossover study with a low and a high dose of the 5HT2A agonist dimethyltryptamine (DMT) and the NMDA antagonist S-ketamine. During electroencephalographic recording, the subjects were performing the AX-version of a continuous performance test (AX-CPT). A source analysis of MMN was performed on the basis of a four-source model of MMN generation. RESULTS: Nine subjects completed both experimental days with the two doses of both drugs. Overall, we found blunted MMN and performance deficits in the AX-CPT after both drugs. However, the reduction in MMN activity was overall more pronounced after S-ketamine intake, and only S-ketamine had a significant impact on the frontal source of MMN. CONCLUSIONS: The NDMA antagonist model and the 5HT2A agonist model of psychosis display distinct neurocognitive profiles. These findings are in line with the view of the two classes of hallucinogens modeling different aspects of psychosis

Pharmacological modulation of the neural basis underlying inhibition of return (IOR) in the human 5-HT2A agonist and NMDA antagonist model of psychosis

RATIONALE: Attentional deficits are common symptoms in schizophrenia. Recent evidence suggests that schizophrenic patients show abnormalities in spatial orienting of attention, particularly a deficit of inhibition of return (IOR). IOR is mostly thought to reflect an automatic, inhibitory mechanism protecting the organism from redirecting attention to previously scanned, insignificant locations. Pharmacologic challenges with hallucinogens have been used as models for psychosis. OBJECTIVES: The aim of this study was to investigate the neural correlates underlying orienting of attention in the human N-methyl-D-aspartic acid antagonist and 5-HT2A agonist models of psychosis. MATERIALS AND METHODS: Fourteen healthy volunteers participated in a randomized, double-blind, cross-over event-related functional magnetic resonance imaging (fMRI) study with dimethyltryptamine (DMT) and S-ketamine. We administered a covert orienting of attention task with nonpredictive peripheral cues, and we scanned the subjects on two separate days at least 14 days apart with a placebo and a verum condition on each day. RESULTS: DMT, but not S-ketamine, slowed down reaction times significantly. IOR was blunted after DMT, but not after S-ketamine. Relative to placebo, S-ketamine increased activation in the IOR condition in the right superior frontal gyrus, left superior temporal gyrus, and right midfrontal frontal gyrus. CONCLUSIONS: The discrepancy between the behavioral and functional imaging outcome indicates that pharmacological fMRI might be a sensitive tool to detect drug-modulated blood oxygenation level-dependent signal changes in the absence of behavioral abnormalities. Our findings might help to further clarify the contradictory findings of IOR in schizophrenic patients and might, thus, shed more light on possible differential pathomechanisms of schizophrenic symptoms

Acuerdo 008 (BIS). "Por el cual se adopta la Política Integral para la Prevención y Atención del Consumo de Sustancias Psicoactivas en la Universidad de Córdoba"

Energetic particles are critical components of plasma populations found throughout the universe. In many cases particles are accelerated to relativistic energies and represent a substantial fraction of the total energy of the system, thus requiring extremely efficient acceleration processes. The production of accelerated particles also appears coupled to magnetic field evolution in astrophysical plasmas through the turbulent magnetic fields produced by diffusive shock acceleration. Particle acceleration is thus a key component in helping to understand the origin and evolution of magnetic structures in, e. g. galaxies. The proximity of the Sun and the range of high-resolution diagnostics available within the solar atmosphere offers unique opportunities to study the processes involved in particle acceleration through the use of a combination of remote sensing observations of the radiative signatures of accelerated particles, and of their plasma and magnetic environment. The SPARK concept targets the broad range of energy, spatial and temporal scales over which particle acceleration occurs in the solar atmosphere, in order to determine how and where energetic particles are accelerated. SPARK combines highly complementary imaging and spectroscopic observations of radiation from energetic electrons, protons and ions set in their plasma and magnetic context. The payload comprises focusing-optics X-ray imaging covering the range from 1 to 60 keV; indirect HXR imaging and spectroscopy from 5 to 200 keV, γ-ray spectroscopic imaging with high-resolution LaBr 3 scintillators, and photometry and source localisation at far-infrared wavelengths. The plasma environment of the regions of acceleration and interaction will be probed using soft X-ray imaging of the corona and vector magnetography of the photosphere and chromosphere. SPARK is designed for solar research. However, in addition it will be able to provide exciting new insights into the origin of particle acceleration in other regimes, including terrestrial gamma-ray flashes (TGF), the origin of γ-ray bursts, and the possible existence of axions. © 2011 Springer Science+Business Media B.V