Reversible inactivation of ferret auditory cortex impairs spatial and non-spatial hearing

A key question in auditory neuroscience is to what extent are brain regions functionally specialized for processing specific sound features such as location and identity. In auditory cortex, correlations between neural activity and sounds support both the specialization of distinct cortical subfields, and encoding of multiple sound features within individual cortical areas. However, few studies have tested the contribution of auditory cortex to hearing in multiple contexts. Here we determined the role of ferret primary auditory cortex in both spatial and non-spatial hearing by reversibly inactivating the middle ectosylvian gyrus during behavior using cooling (n=2 females) or optogenetics (n=1 female). Optogenetic experiments utilized the mDLx promoter to express Channelrhodopsin2 in GABAergic interneurons and we confirmed both viral expression (n=2 females) and light-driven suppression of spiking activity in auditory cortex, recorded using Neuropixels under anesthesia (n=465 units from 2 additional untrained female ferrets). Cortical inactivation via cooling or optogenetics impaired vowel discrimination in co-located noise. Ferrets implanted with cooling loops were tested in additional conditions that revealed no deficits for identifying vowels in clean conditions, or when the temporally coincident vowel and noise were spatially separated by 180 degrees. These animals did however show impaired sound localization when inactivating the same auditory cortical region implicated in vowel discrimination in noise. Our results demonstrate that, as a brain region showing mixed selectivity for spatial and non-spatial features of sound, primary auditory cortex contributes to multiple forms of hearing.SIGNIFICANCE STATEMENT:Neurons in primary auditory cortex are often sensitive to the location and identity of sounds. Here we inactivated auditory cortex during spatial and non- spatial listening tasks using cooling, or optogenetics. Auditory cortical inactivation impaired multiple behaviors, demonstrating a role in both the analysis of sound location and identity and confirming a functional contribution of mixed selectivity observed in neural activity. Parallel optogenetic experiments in two additional untrained ferrets linked behavior to physiology by demonstrating that expression of Channelrhodopsin 2 permitted rapid light-driven suppression of auditory cortical activity recorded under anesthesia

Simultaneous Assessment of Speech Identification and Spatial Discrimination: A Potential Testing Approach for Bilateral Cochlear Implant Users?

With increasing numbers of children and adults receiving bilateral cochlear implants, there is an urgent need for assessment tools that enable testing of binaural hearing abilities. Current test batteries are either limited in scope or are of an impractical duration for routine testing. Here, we report a behavioral test that enables combined testing of speech identification and spatial discrimination in noise. In this task, multitalker babble was presented from all speakers, and pairs of speech tokens were sequentially presented from two adjacent speakers. Listeners were required to identify both words from a closed set of four possibilities and to determine whether the second token was presented to the left or right of the first. In Experiment 1, normal-hearing adult listeners were tested at 15° intervals throughout the frontal hemifield. Listeners showed highest spatial discrimination performance in and around the frontal midline, with a decline at more eccentric locations. In contrast, speech identification abilities were least accurate near the midline and showed an improvement in performance at more lateral locations. In Experiment 2, normal-hearing listeners were assessed using a restricted range of speaker locations designed to match those found in clinical testing environments. Here, speakers were separated by 15° around the midline and 30° at more lateral locations. This resulted in a similar pattern of behavioral results as in Experiment 1. We conclude, this test offers the potential to assess both spatial discrimination and the ability to use spatial information for unmasking in clinical populations

Facilitating Design-by-Analogy: Development of a Complete Functional Vocabulary and Functional Vector Approach to Analogical Search

Design-by-analogy is an effective approach to innovative concept generation, but can be elusive at times due to the fact that few methods and tools exist to assist designers in systematically seeking and identifying analogies from general data sources, databases, or repositories, such as patent databases. A new method for extracting analogies from data sources has been developed to provide this capability. Building on past research, we utilize a functional vector space model to quantify analogous similarity between a design problem and the data source of potential analogies. We quantitatively evaluate the functional similarity between represented design problems and, in this case, patent descriptions of products. We develop a complete functional vocabulary to map the patent database to applicable functionally critical terms, using document parsing algorithms to reduce text descriptions of the data sources down to the key functions, and applying Zipf’s law on word count order reduction to reduce the words within the documents. The reduction of a document (in this case a patent) into functional analogous words enables the matching to novel ideas that are functionally similar, which can be customized in various ways. This approach thereby provides relevant sources of design-by-analogy inspiration. Although our implementation of the technique focuses on functional descriptions of patents and the mapping of these functions to those of the design problem, resulting in a set of analogies, we believe that this technique is applicable to other analogy data sources as well. As a verification of the approach, an original design problem for an automated window washer illustrates the distance range of analogical solutions that can be extracted, extending from very near-field, literal solutions to far-field cross-domain analogies. Finally, a comparison with a current patent search tool is performed to draw a contrast to the status quo and evaluate the effectiveness of this work.National Science Foundation (U.S.) (grant number CMMI-0855510)National Science Foundation (U.S.) (grant number CMMI-0855326)National Science Foundation (U.S.) (grant number CMMI-0855293)SUTD-MIT International Design Centre (IDC

Stability of spontaneous, correlated activity in mouse auditory cortex

Neural systems can be modeled as networks of functionally connected neural elements. The resulting network can be analyzed using mathematical tools from network science and graph theory to quantify the system's topological organization and to better understand its function. While the network-based approach is common in the analysis of large-scale neural systems probed by non-invasive neuroimaging, few studies have used network science to study the organization of networks reconstructed at the cellular level, and thus many very basic and fundamental questions remain unanswered. Here, we used two-photon calcium imaging to record spontaneous activity from the same set of cells in mouse auditory cortex over the course of several weeks. We reconstruct functional networks in which cells are linked to one another by edges weighted according to the correlation of their fluorescence traces. We show that the networks exhibit modular structure across multiple topological scales and that these multi-scale modules unfold as part of a hierarchy. We also show that, on average, network architecture becomes increasingly dissimilar over time, with similarity decaying monotonically with the distance (in time) between sessions. Finally, we show that a small fraction of cells maintain strongly-correlated activity over multiple days, forming a stable temporal core surrounded by a fluctuating and variable periphery. Our work provides a careful methodological blueprint for future studies of spontaneous activity measured by two-photon calcium imaging using cutting-edge computational methods and machine learning algorithms informed by explicit graphical models from network science. The methods are easily extended to additional datasets, opening the possibility of studying cellular level network organization of neural systems and how that organization is modulated by stimuli or altered in models of disease.Comment: 15 pages, 3 figure

The effect of relative plasma plume delay on the properties of complex oxide films grown by multi-laser multi-target combinatorial pulsed laser deposition

We report the effects of relative time delay of plasma plumes on thin garnet crystal films fabricated by dual-beam, combinatorial pulsed laser deposition. Relative plume delay was found to affect both the lattice constant and elemental composition of mixed Gd3Ga5O12 (GGG) and Gd3Sc2Ga5O12 (GSGG) films. Further analysis of the plasmas was undertaken using a Langmuir probe, which revealed that for relative plume delays shorter than ~200 µs, the second plume travels through a partial vacuum created by the first plume, leading to higher energy ion bombardment of the growing film. The resulting in-plane stresses are consistent with the transition to a higher value of lattice constant normal to the film plane that was observed around this delay value. At delays shorter than ~10 µs, plume propagation was found to overlap, leading to scattering of lighter ions from the plume and a change in stoichiometry of the resultant films

Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis

There is growing evidence for an interplay between inflammatory and coagulation pathways in acute and chronic inflammatory diseases. However, it remains unclear whether components of the coagulation pathway, such as tissue factor (TF), contribute to intestinal inflammation, and whether targeting TF will blunt the inflammatory cell recruitment, tissue injury, and enhanced thrombus formation that occur in experimental colitis. Mice were fed 3% dextran sodium sulfate (DSS) to induce colonic inflammation, with some mice receiving a mouse TF-blocking antibody (muTF-Ab). The adhesion of leukocytes and platelets in colonic venules, light/dye-induced thrombus formation in cremaster muscle microvessels, as well as disease activity index, thrombin–antithrombin (TAT) complexes in plasma, and histopathologic changes in the colonic mucosa were monitored in untreated and muTF-Ab–treated colitic mice. In untreated mice, DSS elicited the recruitment of adherent leukocytes and platelets in colonic venules, caused gross and histologic injury, increased plasma TAT complexes, and enhanced thrombus formation in muscle arterioles. muTF-Ab prevented elevation in TAT complexes, reduced blood cell recruitment and tissue injury, and blunted thrombus formation in DSS colitic mice. These findings implicate TF in intestinal inflammation and support an interaction between inflammation and coagulation in experimental colitis

Relative sound localisation abilities in human listeners

Spatial acuity varies with sound-source azimuth, signal-to-noise ratio, and the spectral characteristics of the sound source. Here, the spatial localisation abilities of listeners were assessed using a relative localisation task. This task tested localisation ability at fixed angular separations throughout space using a two-alternative forced-choice design across a variety of listening conditions. Subjects were required to determine whether a target sound originated to the left or right of a preceding reference in the presence of a multi-source noise background. Experiment 1 demonstrated that subjects' ability to determine the relative location of two sources declined with less favourable signal-to-noise ratios and at peripheral locations. Experiment 2 assessed performance with both broadband and spectrally restricted stimuli designed to limit localisation cues to predominantly interaural level differences or interaural timing differences (ITDs). Predictions generated from topographic, modified topographic, and two-channel models of sound localisation suggest that for low-pass stimuli, where ITD cues were dominant, the two-channel model provides an adequate description of the experimental data, whereas for broadband and high frequency bandpass stimuli none of the models was able to fully account for performance. Experiment 3 demonstrated that relative localisation performance was uninfluenced by shifts in gaze direction