Lus (four), whereas the P3 is thought to reflect the redirection of interest to that deviant stimulus (5). In an MAO-B Inhibitor drug oddball paradigm, responses to deviant (or “oddball”) stimuli occurring among a sequence of normal stimuli are measured. The MMN is obtained by subtracting the ERP for the standard stimulus from the ERP towards the deviant stimulus, whereas the P3a is generally observed within the ERP to deviants. Schizophrenia patients appear significantly less able to detect and direct interest to novel stimuli than wholesome controls (6). Constant with this behavioral deficit, the amplitudes of each the MMN (7) plus the P3 (eight) have already been identified to become lowered in schizophrenia patients, top towards the proposals that lowered MMN is usually a marker of progressive pathology (7) and that reductions in each MMN and P3a are markers of vulnerability for this disorder (eight, 9). Given the homology of human and rhesus macaque brains (ten), the development of a nonhuman primate (NHP) model ofpnas.org/cgi/doi/10.1073/pnas.SResultsComparison of MMN in Humans and Monkeys. The MMN isobtained by subtracting the ERP to the common stimulus in the ERP to the deviant stimulus (see Components and Solutions). In humans, the auditory MMN is well documented as a frontocentral unfavorable prospective using a latency of 10050 ms immediately after the onset of stimulus presentation and has sources in auditory cortices and within the inferior frontal gyrus (14). Constant withAuthor contributions: R.G.-d.-C., G.R.S., R.F., and T.D.A. developed study; R.G.-d.-C. and R.F. performed investigation; R.G.-d.-C. and R.F. analyzed information; and R.G.-d.-C., G.R.S., R.F., and T.D.A. wrote the paper. The authors declare no conflict of interest. Freely out there on the web by means of the PNAS open access choice. See Commentary on web page 15175.To whom correspondence may very well be addressed. E-mail: [email protected] or [email protected] short article contains supporting information on the web at pnas.org/lookup/suppl/doi:ten. 1073/pnas.1312264110/-/DCSupplemental.PNAS | September 17, 2013 | vol. 110 | no. 38 | 15425PSYCHOLOGICAL AND COGNITIVE SCIENCESThere is expanding evidence that impaired sensory-processing significantly contributes towards the cognitive deficits located in schizophrenia. For example, the mismatch negativity (MMN) and P3a event-related potentials (ERPs), neurophysiological indices of sensory and cognitive function, are decreased in schizophrenia patients and could be made use of as biomarkers with the disease. In agreement with glutamatergic theories of schizophrenia, NMDA antagonists, including ketamine, elicit many symptoms of schizophrenia when administered to regular subjects, which includes reductions within the MMN as well as the P3a. We sought to develop a nonhuman primate (NHP) model of schizophrenia based on NMDA-receptor blockade utilizing subanesthetic administration of ketamine. This provided neurophysiological measures of sensory and cognitive function that were straight comparable to these recorded from humans. We first created solutions that permitted recording of ERPs from humans and rhesus macaques and found homologous MMN and P3a ERPs throughout an auditory oddball paradigm. We then investigated the effect of ketamine on these ERPs in macaques. As found in humans with schizophrenia, too as in standard subjects provided ketamine, we observed a substantial decrease in amplitude of both ERPs. Our findings Plasmodium Inhibitor list recommend the potential of a pharmacologically induced model of schizophrenia in NHPs that may pave the way for EEG-guided investigations into cellular mechanisms and therapies. Furthermo.
