title: Dexamphetamine reduces auditory P3 delta power and phase-locking while increasing gamma power.
abstract: Auditory P3 amplitude reduction is one of the most robust and replicated findings in schizophrenia. Recent evidence suggests that these reductions are due to reductions in both power and phase-locking at delta and theta frequencies. We have previously shown that the auditory, but not visual, P3 is reduced in healthy participants given the catecholamine releasing agent dexamphetamine. Our aim was to determine whether the auditory P3 amplitude reduction induced by dexamphetamine has similar power and phase locking characteristics to that seen in schizophrenia. Forty-four healthy participants were given 0.45 mg/kg dexamphetamine and placebo, in a double-blinded, placebo-controlled, cross-over design. The task was a three-stimulus auditory odd-ball task, target stimuli were the major stimuli of interest. Individual target trials underwent wavelet analysis to give power and phase-locking of delta (3 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13-30 Hz) and gamma (30-50 Hz) frequencies for a 50 ms time window centred around the peak of the target P3. Delta power around the P3 peak was significantly reduced when participants were given dexamphetamine. Delta phase-locking was also reduced but only when analysis was targeted at the location of the peak P3 amplitude. In contrast, theta power and phase-locking were not affected by dexamphetamine. These findings suggest that increased catecholamine activity may be responsible for the power and phase-locking reductions of the auditory P3 delta component in patients with schizophrenia. Interestingly, dexamphetamine significantly increased gamma power around the P3 peak. We attempt to link this finding with the gamma alterations that have been found in patients with schizophrenia.
authors.affiliation: Pharmacology & Anaesthesiology Unit, School of Medicine and Pharmacology, The University of Western Australia, Centre for Clinical Research in Neuropsychiatry, Graylands Hospital, Australia. albrem04@student.uwa.edu.au
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Albrecht
authors.forename: Greg
authors.initials: G
authors.lastname: Price
authors.forename: Joseph
authors.initials: J
authors.lastname: Lee
authors.forename: Rajan
authors.initials: R
authors.lastname: Iyyalol
authors.forename: Mathew T
authors.initials: MT
authors.lastname: Martin-Iverson
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology; D001306:Auditory Pathways / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects*; D004569:Electroencephalography / Q000187:drug effects; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018765:Dopamine Uptake Inhibitors; D003913:Dextroamphetamine; D004298:Dopamine