AIM: A network model of attention in auditory cortex.

Attentional modulation of cortical networks is critical for the cognitive flexibility required to process complex scenes. Current theoretical frameworks for attention are based almost exclusively on studies in visual cortex, where attentional effects are typically modest and excitatory. In contrast, attentional effects in auditory cortex can be large and suppressive. A theoretical framework for explaining attentional effects in auditory cortex is lacking, preventing a broader understanding of cortical mechanisms underlying attention. Here, we present a cortical network model of attention in primary auditory cortex (A1). A key mechanism in our network is attentional inhibitory modulation (AIM) of cortical inhibitory neurons. In this mechanism, top-down inhibitory neurons disinhibit bottom-up cortical circuits, a prominent circuit motif observed in sensory cortex. Our results reveal that the same underlying mechanisms in the AIM network can explain diverse attentional effects on both spatial and frequency tuning in A1. We find that a dominant effect of disinhibition on cortical tuning is suppressive, consistent with experimental observations. Functionally, the AIM network may play a key role in solving the cocktail party problem. We demonstrate how attention can guide the AIM network to monitor an acoustic scene, select a specific target, or switch to a different target, providing flexible outputs for solving the cocktail party problem.

Bi-directional audiovisual influences on temporal modulation discrimination.

Cross-modal interactions of auditory and visual temporal modulation were examined in a game-like experimental framework. Participants observed an audiovisual stimulus (an animated, sound-emitting fish) whose sound intensity and/or visual size oscillated sinusoidally at either 6 or 7 Hz. Participants made speeded judgments about the modulation rate in either the auditory or visual modality while doing their best to ignore information from the other modality. Modulation rate in the task-irrelevant modality matched the modulation rate in the task-relevant modality (congruent conditions), was at the other rate (incongruent conditions), or had no modulation (unmodulated conditions). Both performance accuracy and parameter estimates from drift-diffusion decision modeling indicated that (1) the presence of temporal modulation in both modalities, regardless of whether modulations were matched or mismatched in rate, resulted in audiovisual interactions; (2) congruence in audiovisual temporal modulation resulted in more reliable information processing; and (3) the effects of congruence appeared to be stronger when judging visual modulation rates (i.e., audition influencing vision), than when judging auditory modulation rates (i.e., vision influencing audition). The results demonstrate that audiovisual interactions from temporal modulations are bi-directional in nature, but with potential asymmetries in the size of the effect in each direction.

Förster Resonance Energy Transfer between Quantum Dot Donors and Quantum Dot Acceptors.

Förster (or fluorescence) resonance energy transfer amongst semiconductor quantum dots (QDs) is reviewed, with particular interest in biosensing applications. The unique optical properties of QDs provide certain advantages and also specific challenges with regards to sensor design, compared to other FRET systems. The brightness and photostability of QDs make them attractive for highly sensitive sensing and long-term, repetitive imaging applications, respectively, but the overlapping donor and acceptor excitation signals that arise when QDs serve as both the donor and acceptor lead to high background signals from direct excitation of the acceptor. The fundamentals of FRET within a nominally homogeneous QD population as well as energy transfer between two distinct colors of QDs are discussed. Examples of successful sensors are highlighted, as is cascading FRET, which can be used for solar harvesting.

A biologically oriented algorithm for spatial sound segregation.

Listening in an acoustically cluttered scene remains a difficult task for both machines and hearing-impaired listeners. Normal-hearing listeners accomplish this task with relative ease by segregating the scene into its constituent sound sources, then selecting and attending to a target source. An assistive listening device that mimics the biological mechanisms underlying this behavior may provide an effective solution for those with difficulty listening in acoustically cluttered environments (e.g., a cocktail party). Here, we present a binaural sound segregation algorithm based on a hierarchical network model of the auditory system. In the algorithm, binaural sound inputs first drive populations of neurons tuned to specific spatial locations and frequencies. The spiking response of neurons in the output layer are then reconstructed into audible waveforms via a novel reconstruction method. We evaluate the performance of the algorithm with a speech-on-speech intelligibility task in normal-hearing listeners. This two-microphone-input algorithm is shown to provide listeners with perceptual benefit similar to that of a 16-microphone acoustic beamformer. These results demonstrate the promise of this biologically inspired algorithm for enhancing selective listening in challenging multi-talker scenes.

A Physiologically Inspired Model for Solving the Cocktail Party Problem.

At a cocktail party, we can broadly monitor the entire acoustic scene to detect important cues (e.g., our names being called, or the fire alarm going off), or selectively listen to a target sound source (e.g., a conversation partner). It has recently been observed that individual neurons in the avian field L (analog to the mammalian auditory cortex) can display broad spatial tuning to single targets and selective tuning to a target embedded in spatially distributed sound mixtures. Here, we describe a model inspired by these experimental observations and apply it to process mixtures of human speech sentences. This processing is realized in the neural spiking domain. It converts binaural acoustic inputs into cortical spike trains using a multi-stage model composed of a cochlear filter-bank, a midbrain spatial-localization network, and a cortical network. The output spike trains of the cortical network are then converted back into an acoustic waveform, using a stimulus reconstruction technique. The intelligibility of the reconstructed output is quantified using an objective measure of speech intelligibility. We apply the algorithm to single and multi-talker speech to demonstrate that the physiologically inspired algorithm is able to achieve intelligible reconstruction of an "attended" target sentence embedded in two other non-attended masker sentences. The algorithm is also robust to masker level and displays performance trends comparable to humans. The ideas from this work may help improve the performance of hearing assistive devices (e.g., hearing aids and cochlear implants), speech-recognition technology, and computational algorithms for processing natural scenes cluttered with spatially distributed acoustic objects.

Coordinated regulation of acid resistance in Escherichia coli.

BACKGROUND: Enteric Escherichia coli survives the highly acidic environment of the stomach through multiple acid resistance (AR) mechanisms. The most effective system, AR2, decarboxylates externally-derived glutamate to remove cytoplasmic protons and excrete GABA. The first described system, AR1, does not require an external amino acid. Its mechanism has not been determined. The regulation of the multiple AR systems and their coordination with broader cellular metabolism has not been fully explored. RESULTS: We utilized a combination of ChIP-Seq and gene expression analysis to experimentally map the regulatory interactions of four TFs: nac, ntrC, ompR, and csiR. Our data identified all previously in vivo confirmed direct interactions and revealed several others previously inferred from gene expression data. Our data demonstrate that nac and csiR directly modulate AR, and leads to a regulatory network model in which all four TFs participate in coordinating acid resistance, glutamate metabolism, and nitrogen metabolism. This model predicts a novel mechanism for AR1 by which the decarboxylation enzymes of AR2 are used with internally derived glutamate. This hypothesis makes several testable predictions that we confirmed experimentally. CONCLUSIONS: Our data suggest that the regulatory network underlying AR is complex and deeply interconnected with the regulation of GABA and glutamate metabolism, nitrogen metabolism. These connections underlie and experimentally validated model of AR1 in which the decarboxylation enzymes of AR2 are used with internally derived glutamate.

Effectiveness of different intracanal irrigation techniques in removing intracanal paste medicaments.

This study aimed to compare the effectiveness of different intracanal irrigation techniques in removing intracanal medicaments prior to obturation. A total of 168 single roots were prepared with ProTaper® rotary files and medicament pastes applied (Ledermix®, Odontopaste®, Doxypaste and Pulpdent®), left in for 2 weeks, then removed using filing followed by one of four methods: irrigation with an open-ended notched irrigation needle (Appli-Vac) either at the working length or 5 mm from the canal orifice, or the Max-I-probe or EndoActivator® at the working length. Following the removal of medicaments, the roots were split into two and the internal surfaces photographed, for digital image analysis of the overall percentage of residual medicament. With the exception of canals irrigated 5 mm apical to the root canal orifice, all four irrigation techniques achieved an average of 95% for removal of Ledermix®, Odontopaste® and Doxypaste. Calcium hydroxide paste was the most difficult medicament to remove, with no difference between irrigation techniques. Up to 27% of the Pulpdent® material remained after irrigation. No irrigation technique could completely remove all traces of medicaments. The position of the irrigational needle and the type of medicament used are key factors, which influence the effectiveness of irrigation in removing medicaments.