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Ketamine effects on brain function--simultaneous fMRI/EEG during a visual oddball task.
Neuroimage 2011; 58(2):508-25N

Abstract

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.

Authors+Show Affiliations

Institute of Neurosciences and Medicine, Helmholtz Research Center, Jülich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21723949

Citation

Musso, Francesco, et al. "Ketamine Effects On Brain Function--simultaneous fMRI/EEG During a Visual Oddball Task." NeuroImage, vol. 58, no. 2, 2011, pp. 508-25.
Musso F, Brinkmeyer J, Ecker D, et al. Ketamine effects on brain function--simultaneous fMRI/EEG during a visual oddball task. Neuroimage. 2011;58(2):508-25.
Musso, F., Brinkmeyer, J., Ecker, D., London, M. K., Thieme, G., Warbrick, T., ... Winterer, G. (2011). Ketamine effects on brain function--simultaneous fMRI/EEG during a visual oddball task. NeuroImage, 58(2), pp. 508-25. doi:10.1016/j.neuroimage.2011.06.045.
Musso F, et al. Ketamine Effects On Brain Function--simultaneous fMRI/EEG During a Visual Oddball Task. Neuroimage. 2011 Sep 15;58(2):508-25. PubMed PMID: 21723949.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ketamine effects on brain function--simultaneous fMRI/EEG during a visual oddball task. AU - Musso,Francesco, AU - Brinkmeyer,Jürgen, AU - Ecker,Daniel, AU - London,Markus K, AU - Thieme,Giesela, AU - Warbrick,Tracy, AU - Wittsack,Hans-Jörg, AU - Saleh,Andreas, AU - Greb,Wolfgang, AU - de Boer,Peter, AU - Winterer,Georg, Y1 - 2011/06/29/ PY - 2011/01/31/received PY - 2011/06/09/revised PY - 2011/06/17/accepted PY - 2011/7/5/entrez PY - 2011/7/5/pubmed PY - 2011/12/22/medline SP - 508 EP - 25 JF - NeuroImage JO - Neuroimage VL - 58 IS - 2 N2 - 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. SN - 1095-9572 UR - https://www.unboundmedicine.com/medline/citation/21723949/Ketamine_effects_on_brain_function__simultaneous_fMRI/EEG_during_a_visual_oddball_task_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1053-8119(11)00690-2 DB - PRIME DP - Unbound Medicine ER -