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Ketamine effects on CNS responses assessed with MEG/EEG in a passive auditory sensory-gating paradigm: an attempt for modelling some symptoms of psychosis in man.
J Psychopharmacol 2007; 21(3):321-37JP

Abstract

Disturbances in integrative function have been consistentLy described in psychotic disorder; for instance, prepulse inhibition of the startle reflex (startle-PPI) which is a marker of sensory gating, is deficient in persons with schizophrenia. The N-methyl-D-aspartate antagonist ketamine produces in control subjects a spectrum of neurobehavioural symptoms like encountered in schizophrenia, and disrupts startle-PPI in animals. In the present study, we investigated in 12 healthy subjects whether ketamine would reduce sensory-gating in auditory responses at doses which produce psychotic symptoms. In a double-blind, crossover design loading doses of 0.024, 0.081 and 0.27 mg/kg or saline were employed, followed by maintenance infusion for 120 min. A passive paradigm has been developed which consisted in tone bursts, preceded or not by a (near-threshold) click at intervals of 100 ms or 500 ms. Brain electromagnetic activity imaging of the responses to sound stimuli has been carried out by way of a 148-channel magnetoencephalography-system. Actual evoked response amplitudes and underlying equivalent current dipole strengths have been compared to multi-electrode evoked potentials from the scalp. A click stimulus is capable to inhibit test responses under placebo at the 100 ms interval. During maintenance infusion of ketamine at steady-state (for >30 min) after 0.27 mg/kg, no such amplitude changes were observed anymore (p <0.05) and under these circumstances significant increases in Brief Psychiatric Rating scale and Scale for the Assessment of Negative Symptoms scores were evidenced (p < 0.001). Intermediate effects have been observed when the dose was lowered to 0.081 mg/kg. The present results have shown that ketamine may induce a psychotic-like clinical state associated with gating deficits in healthy subjects.

Authors+Show Affiliations

FORENAP - FRP - Institute for Research in Neuroscience, Neuropharmacology and Psychiatry, Rouffach, France. Peter.Boeijinga@forenap.com [corrected]No 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

17591659

Citation

Boeijinga, Peter H., et al. "Ketamine Effects On CNS Responses Assessed With MEG/EEG in a Passive Auditory Sensory-gating Paradigm: an Attempt for Modelling some Symptoms of Psychosis in Man." Journal of Psychopharmacology (Oxford, England), vol. 21, no. 3, 2007, pp. 321-37.
Boeijinga PH, Soufflet L, Santoro F, et al. Ketamine effects on CNS responses assessed with MEG/EEG in a passive auditory sensory-gating paradigm: an attempt for modelling some symptoms of psychosis in man. J Psychopharmacol (Oxford). 2007;21(3):321-37.
Boeijinga, P. H., Soufflet, L., Santoro, F., & Luthringer, R. (2007). Ketamine effects on CNS responses assessed with MEG/EEG in a passive auditory sensory-gating paradigm: an attempt for modelling some symptoms of psychosis in man. Journal of Psychopharmacology (Oxford, England), 21(3), pp. 321-37.
Boeijinga PH, et al. Ketamine Effects On CNS Responses Assessed With MEG/EEG in a Passive Auditory Sensory-gating Paradigm: an Attempt for Modelling some Symptoms of Psychosis in Man. J Psychopharmacol (Oxford). 2007;21(3):321-37. PubMed PMID: 17591659.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ketamine effects on CNS responses assessed with MEG/EEG in a passive auditory sensory-gating paradigm: an attempt for modelling some symptoms of psychosis in man. AU - Boeijinga,Peter H, AU - Soufflet,L, AU - Santoro,F, AU - Luthringer,R, PY - 2007/6/27/pubmed PY - 2007/8/29/medline PY - 2007/6/27/entrez SP - 321 EP - 37 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 21 IS - 3 N2 - Disturbances in integrative function have been consistentLy described in psychotic disorder; for instance, prepulse inhibition of the startle reflex (startle-PPI) which is a marker of sensory gating, is deficient in persons with schizophrenia. The N-methyl-D-aspartate antagonist ketamine produces in control subjects a spectrum of neurobehavioural symptoms like encountered in schizophrenia, and disrupts startle-PPI in animals. In the present study, we investigated in 12 healthy subjects whether ketamine would reduce sensory-gating in auditory responses at doses which produce psychotic symptoms. In a double-blind, crossover design loading doses of 0.024, 0.081 and 0.27 mg/kg or saline were employed, followed by maintenance infusion for 120 min. A passive paradigm has been developed which consisted in tone bursts, preceded or not by a (near-threshold) click at intervals of 100 ms or 500 ms. Brain electromagnetic activity imaging of the responses to sound stimuli has been carried out by way of a 148-channel magnetoencephalography-system. Actual evoked response amplitudes and underlying equivalent current dipole strengths have been compared to multi-electrode evoked potentials from the scalp. A click stimulus is capable to inhibit test responses under placebo at the 100 ms interval. During maintenance infusion of ketamine at steady-state (for >30 min) after 0.27 mg/kg, no such amplitude changes were observed anymore (p <0.05) and under these circumstances significant increases in Brief Psychiatric Rating scale and Scale for the Assessment of Negative Symptoms scores were evidenced (p < 0.001). Intermediate effects have been observed when the dose was lowered to 0.081 mg/kg. The present results have shown that ketamine may induce a psychotic-like clinical state associated with gating deficits in healthy subjects. SN - 0269-8811 UR - https://www.unboundmedicine.com/medline/citation/17591659/Ketamine_effects_on_CNS_responses_assessed_with_MEG/EEG_in_a_passive_auditory_sensory_gating_paradigm:_an_attempt_for_modelling_some_symptoms_of_psychosis_in_man_ L2 - http://journals.sagepub.com/doi/full/10.1177/0269881107077768?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -