Revisiting the left ear advantage for phonetic cues to talker identification.

Previous research suggests that learning to use a phonetic property [e.g., voice-onset-time, (VOT)] for talker identity supports a left ear processing advantage. Specifically, listeners trained to identify two "talkers" who only differed in characteristic VOTs showed faster talker identification for stimuli presented to the left ear compared to that presented to the right ear, which is interpreted as evidence of hemispheric lateralization consistent with task demands. Experiment 1 (n = 97) aimed to replicate this finding and identify predictors of performance; experiment 2 (n = 79) aimed to replicate this finding under conditions that better facilitate observation of laterality effects. Listeners completed a talker identification task during pretest, training, and posttest phases. Inhibition, category identification, and auditory acuity were also assessed in experiment 1. Listeners learned to use VOT for talker identity, which was positively associated with auditory acuity. Talker identification was not influenced by ear of presentation, and Bayes factors indicated strong support for the null. These results suggest that talker-specific phonetic variation is not sufficient to induce a left ear advantage for talker identification; together with the extant literature, this instead suggests that hemispheric lateralization for talker-specific phonetic variation requires phonetic variation to be conditioned on talker differences in source characteristics.

Functional characterization and high-throughput screening of positive allosteric modulators of α7 nicotinic acetylcholine receptors in IMR-32 neuroblastoma cells.

α7 nicotinic acetylcholine receptors (nAChRs) are characterized by relatively low ACh sensitivity, rapid activation, and fast desensitization kinetics. ACh/agonist evoked currents at the α7 nAChR are transient, and, typically, calcium flux responses are difficult to detect using conventional fluorometric assay techniques. One approach to study interactions of agonists with the α7 nAChR is by utilizing positive allosteric modulators (PAMs). In this study, we demonstrate that inclusion of type II PAMs such as PNU-120596, but not type I, can enable detection of endogenous α7 nAChR-mediated calcium responses in human neuroblastoma (IMR-32) cells. Using this approach, we characterized the pharmacological profile of nicotine, epibatidine, choline, and other nAChR agonists such as PNU-282987, SSR-180711, GTS-21, OH-GTS21, tropisetron, NS6784, and A-582941. The rank order potency of agonists well correlated with α7 nAChR binding affinities measured in brain membranes. Inhibition of calcium response by methyllycaconitine in the presence of increasing concentrations of PNU-282987 or PNU-120596 revealed that the IC(50) value of methyllycaconitine was sensitive to varying concentrations of the agonist, but not that of the PAM. This format demonstrated the feasibility of this approach for high-throughput screening to identify small molecule, PAMs, which were further confirmed in electrophysiological assays of human α7 nAChR expressed in oocytes.