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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. Beyond the positive and negative clinical symptoms, deficits in early auditory prediction-error processes are also observed in SCZ. 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. 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.ConclusionsThese 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.

Behavioral studies have shown that nicotine enhances performance in sustained attention tasks, but they have not shown convincing support for the effects of nicotine on tasks requiring selective attention or attentional control under conditions of distraction. We investigated distractibility in 14 smokers (7 females) with event-related brain potentials (ERPs) and behavioral performance measures extracted from an auditory discrimination task requiring a choice reaction time response to short- and long-duration tones, both with and without embedded deviants. Nicotine gum (4 mg), administered in a randomized, double-blind, placebo-controlled crossover design, failed to counter deviant-elicited behavioral distraction (i.e., slower reaction times and increased response errors), and it did not influence the distracter-elicited mismatch negativity, the P300a, or the reorienting negativity ERP components reflecting acoustic change detection, involuntary attentional switching, and attentional reorienting, respectively. Results are discussed in relation to a stimulus-filter model of smoking and in relation to future research directions.