BACKGROUND: Behavioral and electrophysiological human ketamine models of schizophrenia are used for testing compounds that target the glutamatergic system. However, corresponding functional neuroimaging models are difficult to reconcile with functional imaging and electrophysiological findings in schizophrenia. Resolving the discrepancies between different observational levels is critical to understand the complex pharmacological ketamine action and its usefulness for modeling schizophrenia pathophysiology. METHODS: We conducted a within-subject, randomized, placebo-controlled pharmacoimaging study in twenty-four male volunteers. Subjects were given low-dose S-ketamine (bolus prior to functional imaging: 0.1mg/kg during 5min, thereafter continuous infusion: 0.015625mg/kg/min reduced by 10% every ten minutes) or placebo while performing a visual oddball task during simultaneous functional magnetic resonance imaging (fMRI) with continuous recording of event-related potentials (P300) and electrodermal activity (EDA). Before and after intervention, psychopathological status was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Altered State of Consciousness (5D-ASC) Rating Scale. RESULTS:P300 amplitude and corresponding BOLD responses were diminished in the ketamine condition in cortical regions being involved in sensory processing/selective attention. In both measurement modalities separation of drug conditions was achieved with area under the curve (AUC) values of up to 0.8-0.9. Ketamine effects were also observed in the clinical, behavioral and peripheral physiological domains (Positive and Negative Syndrome Scale, reaction hit and false alarm rate, electrodermal activity and heart rate) which were in part related to the P300/fMRI measures. CONCLUSION: The findings from our ketamine experiment are consistent across modalities and directly related to observations in schizophrenia supporting the validity of the model. Our investigation provides the first prototypic example of a pharmacoimaging study using simultaneously acquired fMRI/EEG.
RCT Entities:
BACKGROUND: Behavioral and electrophysiological humanketamine models of schizophrenia are used for testing compounds that target the glutamatergic system. However, corresponding functional neuroimaging models are difficult to reconcile with functional imaging and electrophysiological findings in schizophrenia. Resolving the discrepancies between different observational levels is critical to understand the complex pharmacological ketamine action and its usefulness for modeling schizophrenia pathophysiology. METHODS: We conducted a within-subject, randomized, placebo-controlled pharmacoimaging study in twenty-four male volunteers. Subjects were given low-dose S-ketamine (bolus prior to functional imaging: 0.1mg/kg during 5min, thereafter continuous infusion: 0.015625mg/kg/min reduced by 10% every ten minutes) or placebo while performing a visual oddball task during simultaneous functional magnetic resonance imaging (fMRI) with continuous recording of event-related potentials (P300) and electrodermal activity (EDA). Before and after intervention, psychopathological status was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Altered State of Consciousness (5D-ASC) Rating Scale. RESULTS: P300 amplitude and corresponding BOLD responses were diminished in the ketamine condition in cortical regions being involved in sensory processing/selective attention. In both measurement modalities separation of drug conditions was achieved with area under the curve (AUC) values of up to 0.8-0.9. Ketamine effects were also observed in the clinical, behavioral and peripheral physiological domains (Positive and Negative Syndrome Scale, reaction hit and false alarm rate, electrodermal activity and heart rate) which were in part related to the P300/fMRI measures. CONCLUSION: The findings from our ketamine experiment are consistent across modalities and directly related to observations in schizophrenia supporting the validity of the model. Our investigation provides the first prototypic example of a pharmacoimaging study using simultaneously acquired fMRI/EEG.
Authors: Pavitra Krishnaswamy; Giorgio Bonmassar; Catherine Poulsen; Eric T Pierce; Patrick L Purdon; Emery N Brown Journal: Neuroimage Date: 2015-07-05 Impact factor: 6.556
Authors: Anna Bravermanová; Michaela Viktorinová; Filip Tylš; Tomáš Novák; Renáta Androvičová; Jakub Korčák; Jiří Horáček; Marie Balíková; Inga Griškova-Bulanova; Dominika Danielová; Přemysl Vlček; Pavel Mohr; Martin Brunovský; Vlastimil Koudelka; Tomáš Páleníček Journal: Psychopharmacology (Berl) Date: 2018-01-05 Impact factor: 4.530
Authors: Frederick S Barrett; Theresa M Carbonaro; Ethan Hurwitz; Matthew W Johnson; Roland R Griffiths Journal: Psychopharmacology (Berl) Date: 2018-07-30 Impact factor: 4.530
Authors: Dawn F Ionescu; Julia M Felicione; Aishwarya Gosai; Cristina Cusin; Philip Shin; Benjamin G Shapero; Thilo Deckersbach Journal: Harv Rev Psychiatry Date: 2018 Nov/Dec Impact factor: 3.732
Authors: Albert R Powers; Mark G Gancsos; Emily S Finn; Peter T Morgan; Philip R Corlett Journal: Psychopathology Date: 2015-09-12 Impact factor: 1.944