ABSTRACT
Objectives@#This study examined the responses to standard stimuli to investigate the mechanisms underlying mismatch negativity (MMN) impairments in schizophrenia. @*Methods@#We obtained MMN data from 68 patients diagnosed with schizophrenia or schizoaffective disorder and 38 healthy controls and analyzed the electrophysiological activity of the responses to two standard stimuli before deviants using time-frequency methods. @*Results@#As a result of RM ANOVA at evoked alpha power, there were differences not only between-subjects (F 1,104=4.35, p<0.05) but also within-subjects (F 1,104=8.62, p<0.01) without groupby-stimulus interaction (F 1,104=1.70, p=0.20). But at single-trial alpha power, there was a difference not between-subjects (F 1,104=3.81, p=0.054), but only within-subjects (F 1,104=10.14, p<0.01) with significant group-by-stimulus interaction (F 1,104=5.71, p<0.05). Moreover, between-group differences were significant in evoked alpha power (t 104=2.02, p<0.05, d=0.41) and single-trial alpha power (t 104=2.49, p<0.01, d=0.50) to standard stimuli presented not at the first instance but second. According to the order that the two standards presented, there were increases of evoked alpha power (t 37=-2.54, p<0.05, d=0.58) and single-trial alpha power (t 37=-3.41, p<0.01, d=0.78) in only the healthy controls. The positive correlations were shown in clinical features between years of education completed and event-related potential amplitude at 100 ms to both standard stimuli (Each Pearson Corr.: r=0.22, p<0.05). @*Conclusion@#These outputs suggest that the P1 alpha oscillation to standards is associated with deficits in the inhibitory control of selective attention relative to cognitive dysfunction in schizophrenia.We could also hypothesize that these deficits are involved in computing prediction errors based on the predictive coding perspective. However, further studies on this hypothesis are necessary.
ABSTRACT
In the present study, we synthesized a series of novel 7-methoxy-N-(substituted phenyl)benzofuran-2-carboxamide derivatives in moderate to good yields and evaluated their neuroprotective and antioxidant activities using primary cultured rat cortical neuronal cells and in vitro cell-free bioassays. Based on our primary screening data with eighteen synthesized derivatives, nine compounds (1a, 1c, 1f, 1i, 1j, 1l, 1p, 1q and 1r) exhibiting considerable protection against the NMDA-induced excitotoxic neuronal cell damage at the concentration of 100 muM were selected for further evaluation. Among the selected derivatives, compound 1f (with -CH3 substitution at R2 position) exhibited the most potent and efficacious neuroprotective action against the NMDA-induced excitotoxicity. Its neuroprotective effect was almost comparable to that of memantine, a well-known NMDA antagonist, at 30 muM concentration. In addition to 1f, compound 1j (with -OH substitution at R3 position) also showed marked anti-excitotoxic effects at both 100 and 300 muM concentrations. These findings suggest that -CH3 substitution at R2 position and, to a lesser degree, -OH substitution at R3 position may be important for exhibiting neuroprotective action against excitotoxic damage. Compound 1j was also found to scavenge 1,1-diphenyl-2-picrylhydrazyl radicals and inhibit in vitro lipid peroxidation in rat brain homogenate in moderate and appreciable degrees. Taken together, our structure-activity relationship studies suggest that the compound with -CH3 substitution at R2 and -OH substitution at R3 positions of the benzofuran moiety might serve as the lead exhibiting potent anti-excitotoxic, ROS scavenging, and antioxidant activities. Further synthesis and evaluation will be necessary to confirm this possibility.