Understanding Pitch Perception as a Hierarchical Process with Top-Down Modulation

Pitch is one of the most important features of natural sounds, underlying the perception of melody in music and prosody in speech. However, the temporal dynamics of pitch processing are still poorly understood. Previous studies suggest that the auditory system uses a wide range of time scales to integrate pitch-related information and that the effective integration time is both task- and stimulus-dependent. None of the existing models of pitch processing can account for such task- and stimulus-dependent variations in processing time scales. This study presents an idealized neurocomputational model, which provides a unified account of the multiple time scales observed in pitch perception. The model is evaluated using a range of perceptual studies, which have not previously been accounted for by a single model, and new results from a neurophysiological experiment. In contrast to other approaches, the current model contains a hierarchy of integration stages and uses feedback to adapt the effective time scales of processing at each stage in response to changes in the input stimulus. The model has features in common with a hierarchical generative process and suggests a key role for efferent connections from central to sub-cortical areas in controlling the temporal dynamics of pitch processing

Pitch Comparisons between Electrical Stimulation of a Cochlear Implant and Acoustic Stimuli Presented to a Normal-hearing Contralateral Ear

Four cochlear implant users, having normal hearing in the unimplanted ear, compared the pitches of electrical and acoustic stimuli presented to the two ears. Comparisons were between 1,031-pps pulse trains and pure tones or between 12 and 25-pps electric pulse trains and bandpass-filtered acoustic pulse trains of the same rate. Three methods—pitch adjustment, constant stimuli, and interleaved adaptive procedures—were used. For all methods, we showed that the results can be strongly influenced by non-sensory biases arising from the range of acoustic stimuli presented, and proposed a series of checks that should be made to alert the experimenter to those biases. We then showed that the results of comparisons that survived these checks do not deviate consistently from the predictions of a widely-used cochlear frequency-to-place formula or of a computational cochlear model. We also demonstrate that substantial range effects occur with other widely used experimental methods, even for normal-hearing listeners

Epigenetic Silencing of Host Cell Defense Genes Enhances Intracellular Survival of the Rickettsial Pathogen Anaplasma phagocytophilum

Intracellular bacteria have evolved mechanisms that promote survival within hostile host environments, often resulting in functional dysregulation and disease. Using the Anaplasma phagocytophilum–infected granulocyte model, we establish a link between host chromatin modifications, defense gene transcription and intracellular bacterial infection. Infection of THP-1 cells with A. phagocytophilum led to silencing of host defense gene expression. Histone deacetylase 1 (HDAC1) expression, activity and binding to the defense gene promoters significantly increased during infection, which resulted in decreased histone H3 acetylation in infected cells. HDAC1 overexpression enhanced infection, whereas pharmacologic and siRNA HDAC1 inhibition significantly decreased bacterial load. HDAC2 does not seem to be involved, since HDAC2 silencing by siRNA had no effect on A. phagocytophilum intracellular propagation. These data indicate that HDAC up-regulation and epigenetic silencing of host cell defense genes is required for A. phagocytophilum infection. Bacterial epigenetic regulation of host cell gene transcription could be a general mechanism that enhances intracellular pathogen survival while altering cell function and promoting disease

Interaction between Attention and Bottom-Up Saliency Mediates the Representation of Foreground and Background in an Auditory Scene

Bottom-up (stimulus-driven) and top-down (attentional) processes interact when a complex acoustic scene is parsed. Both modulate the neural representation of the target in a manner strongly correlated with behavioral performance

Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33–40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi ∼900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short ≤20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant