Pre-stimulus influences on auditory perception arising from sensory representations and decision processes

The qualities of perception depend not only on the sensory inputs but also on the brain state before stimulus presentation. Although the collective evidence from neuroimaging studies for a relation between prestimulus state and perception is strong, the interpretation in the context of sensory computations or decision processes has remained difficult. In the auditory system, for example, previous studies have reported a wide range of effects in terms of the perceptually relevant frequency bands and state parameters (phase/power). To dissociate influences of state on earlier sensory representations and higher-level decision processes, we collected behavioral and EEG data in human participants performing two auditory discrimination tasks relying on distinct acoustic features. Using single-trial decoding, we quantified the relation between prestimulus activity, relevant sensory evidence, and choice in different task-relevant EEG components. Within auditory networks, we found that phase had no direct influence on choice, whereas power in task-specific frequency bands affected the encoding of sensory evidence. Within later-activated frontoparietal regions, theta and alpha phase had a direct influence on choice, without involving sensory evidence. These results delineate two consistent mechanisms by which prestimulus activity shapes perception. However, the timescales of the relevant neural activity depend on the specific brain regions engaged by the respective task

Irregular speech rate dissociates auditory cortical entrainment, evoked responses, and frontal alpha

The entrainment of slow rhythmic auditory cortical activity to the temporal regularities in speech is considered to be a central mechanism underlying auditory perception. Previous work has shown that entrainment is reduced when the quality of the acoustic input is degraded, but has also linked rhythmic activity at similar time scales to the encoding of temporal expectations. To understand these bottom-up and top-down contributions to rhythmic entrainment, we manipulated the temporal predictive structure of speech by parametrically altering the distribution of pauses between syllables or words, thereby rendering the local speech rate irregular while preserving intelligibility and the envelope fluctuations of the acoustic signal. Recording EEG activity in human participants, we found that this manipulation did not alter neural processes reflecting the encoding of individual sound transients, such as evoked potentials. However, the manipulation significantly reduced the fidelity of auditory delta (but not theta) band entrainment to the speech envelope. It also reduced left frontal alpha power and this alpha reduction was predictive of the reduced delta entrainment across participants. Our results show that rhythmic auditory entrainment in delta and theta bands reflect functionally distinct processes. Furthermore, they reveal that delta entrainment is under top-down control and likely reflects prefrontal processes that are sensitive to acoustical regularities rather than the bottom-up encoding of acoustic features

Neural correlates of multisensory reliability and perceptual weights emerge at early latencies during audio-visual integration

To make accurate perceptual estimates observers must take the reliability of sensory information into account. Despite many behavioural studies showing that subjects weight individual sensory cues in proportion to their reliabilities, it is still unclear when during a trial neuronal responses are modulated by the reliability of sensory information, or when they reflect the perceptual weights attributed to each sensory input. We investigated these questions using a combination of psychophysics, EEG based neuroimaging, and single-trial decoding. Our results show that the weighted integration of sensory information in the brain is a dynamic process; effects of sensory reliability on task-relevant EEG components were evident 84ms after stimulus onset, while neural correlates of perceptual weights emerged 120ms after stimulus onset. These neural processes had different underlying sources, arising from sensory and parietal regions respectively. Together these results reveal the temporal dynamics of perceptual and neural audio-visual integration and support the notion of temporally early and functionally specific multisensory processes in the brain

Red, Rank, and Romance in Women Viewing Men

In many nonhuman species of vertebrates, females are attracted to red on male conspecifics. Red is also a signal of male status in many nonhuman vertebrate species, and females show a mating preference for high-status males. These red–attraction and red–status links have been found even when red is displayed on males artificially. In the present research, we document parallels between human and nonhuman females ’ response to male red. Specifically, in a series of 7 experiments we demonstrate that women perceive men to be more attractive and sexually desirable when seen on a red background and in red clothing, and we additionally show that status perceptions are responsible for this red effect. The influence of red appears to be specific to women’s romantic attraction to men: Red did not influence men’s perceptions of other men, nor did it influence women’s perceptions of men’s overall likability, agreeableness, or extraversion. Participants showed no awareness that the research focused on the influence of color. These findings indicate that color not only has aesthetic value but can carry meaning and impact psychological functioning in subtle, important, and provocative ways

Prospective discovery of small molecule enhancers of an E3 ligase-substrate interaction.

Protein-protein interactions (PPIs) governing the recognition of substrates by E3 ubiquitin ligases are critical to cellular function. There is significant therapeutic potential in the development of small molecules that modulate these interactions; however, rational design of small molecule enhancers of PPIs remains elusive. Herein, we report the prospective identification and rational design of potent small molecules that enhance the interaction between an oncogenic transcription factor, β-Catenin, and its cognate E3 ligase, SCFβ-TrCP. These enhancers potentiate the ubiquitylation of mutant β-Catenin by β-TrCP in vitro and induce the degradation of an engineered mutant β-Catenin in a cellular system. Distinct from PROTACs, these drug-like small molecules insert into a naturally occurring PPI interface, with contacts optimized for both the substrate and ligase within the same small molecule entity. The prospective discovery of 'molecular glue' presented here provides a paradigm for the development of small molecule degraders targeting hard-to-drug proteins

Prospective discovery of small molecule enhancers of an E3 ligase-substrate interaction.

Protein-protein interactions (PPIs) governing the recognition of substrates by E3 ubiquitin ligases are critical to cellular function. There is significant therapeutic potential in the development of small molecules that modulate these interactions; however, rational design of small molecule enhancers of PPIs remains elusive. Herein, we report the prospective identification and rational design of potent small molecules that enhance the interaction between an oncogenic transcription factor, β-Catenin, and its cognate E3 ligase, SCFβ-TrCP. These enhancers potentiate the ubiquitylation of mutant β-Catenin by β-TrCP in vitro and induce the degradation of an engineered mutant β-Catenin in a cellular system. Distinct from PROTACs, these drug-like small molecules insert into a naturally occurring PPI interface, with contacts optimized for both the substrate and ligase within the same small molecule entity. The prospective discovery of 'molecular glue' presented here provides a paradigm for the development of small molecule degraders targeting hard-to-drug proteins