![]() The effects of CDP-choline interacted both with deviant type and auditory deviance detection level, with individuals exhibiting low MMNs showing enhanced amplitudes, while those with high MMNs evidenced reduced amplitudes with acute dosing of CDP-choline. Results No significant whole group effects were observed with CDP-choline, and MMN changes were observed only with analysis of subgroups. Methods In this study, the mismatch negativity (MMN) event-related brain potential (ERP), considered one of the few fully developed biomarkers in schizophrenia, was employed: a) to stratify 24 healthy volunteers into subgroups exhibiting low, medium, or high auditory sensory discrimination based on pre-attentive detection of deviant auditory features, and b) to assess their acute response to a low (500 mg) and moderate dose (1000 mg) of CDP-choline, a dietary supplement with selective agonist actions at α7 nAChRs. The use of schizophrenia-associated biomarkers both as endpoints and for segmentation of homogeneous populations for early detection of cognitive enhancing agents has been advanced to enhance the drug discovery process. These results, observed primarily at temporal recording sites overlying the auditory cortex, implicate α7 nAChRs in the enhancement of speech deviance detection and warrant further examination with respect to dysfunctional auditory deviance processing in individuals with SCZ.īackground Alpha 7 nicotinic acetylcholine receptors (α7 nAChR) are prioritized molecular targets for the development of new pharmacological treatments for impaired cognition in schizophrenia. The randomized, double-blinded, placebo-controlled, and counterbalanced design with a baseline stratification method allowed for assessment of individual response differences.ResultsIncreases in MMN generation mediated by the acute CDP-choline/galantamine treatment in individuals with low baseline MMN amplitude for frequency, intensity, duration, and vowel deviants were revealed.Conclusions ![]() Regularity violations activate these mechanisms that are indexed by electroencephalography-derived mismatch negativity (MMN) event-related potentials (ERPs) in response to auditory deviance.Objectives/methodsThis pilot study in thirty-three healthy humans assessed the effects of an optimized α7 nAChR strategy combining CDP-choline (500 mg) with galantamine (16 mg) on speech-elicited MMN amplitude and latency measures. Beyond the positive and negative clinical symptoms, deficits in early auditory prediction-error processes are also observed in SCZ. RationaleThe combination of CDP-choline, an α7 nicotinic acetylcholine receptor (α7 nAChR) agonist, with galantamine, a positive allosteric modulator of nAChRs, is believed to counter the fast desensitization rate of the α7 nAChRs and may be of interest for schizophrenia (SCZ) patients. # indicates significant differences from the Nic-Nic 0.1 mg/kg and Sal-Nic 0.1 mg/kg groups. Asterisks indicate significant differences from the saline group. (E) Motor activity (# beam breaks) (group means+SEM) for the 7 groups of adult rats in the final nicotine (0.4 mg/kg, sc) test. (D) Motor activity for the individual adult rats from the Nic-Nic 0.4 mg/kg group over the 8 test days. Asterisks indicate significant differences between the two groups. (C) Motor activity (# beam breaks) (group means+SEM) for the adult rats that were previously treated with nicotine 0.6 mg/kg or saline during adolescence and tested with nicotine 0.6 mg/kg during adulthood for 8 days. (B) Motor activity (# beam breaks) (group means+SEM) for the adult rats that were previously treated with nicotine 0.4 mg/kg or saline during adolescence and tested with nicotine 0.4 mg/kg during adulthood for 8 days. (A) Motor activity (# beam breaks) (group means+SEM) for the adult rats that were previously treated with nicotine 0.1 mg/kg or saline during adolescence and tested with nicotine 0.1 mg/kg during adulthood for 8 days.
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