Biology subjects

Ross, J. M.

Publications and source records attributed to Ross, J. M..

3 recordsLinked to original sources

bioRxiv2018

Dorsal Premotor Contributions to Auditory Rhythm Perception: Causal Transcranial Magnetic Stimulation Studies of Interval, Tempo, and Phase

It has been suggested that movement planning networks are critical for time perception. The Action Simulation for Auditory Prediction (ASAP) hypothesis proposes that the dorsal auditory stream is involved in predictive beat-based timing through bidirectional interchange between auditory perception and dorsal premotor (dPMC) prediction via parietal regions, as has been supported by brain imaging and transcranial magnetic stimulation (TMS). However, causal impact of dPMC on time perception has not been tested directly. We used a TMS protocol that down-regulates cortical activity, continuous theta burst stimulation (cTBS), to test for causal contributions of left dPMC to time perception. Three experiments measured (1) discrete interval timing perception, and relative beat-based musical timing for (2) tempo perception and (3) phase perception. Perceptual acuity was tested pre- and post-cTBS using a test of sub-second interval discrimination and the Adaptive Beat Alignment Test (A-BAT). We show (N = 30) that cTBS down-regulation of left dPMC interferes with interval timing perception and the ability to detect differences in musical tempo, but not phase. Our data support causal involvement of premotor networks in perceptual timing, supporting a causal role of the left dPMC in accurate interval and musical tempo perception, possibly via dorsal stream interactions with auditory cortex.

neuroscience↗

bioRxiv2017

Olfactory fear conditioning non-specifically enhances glomerular odor responses and increases representational overlap of learned and neutral odors

Associative fear learning produces fear toward the conditioned stimulus (CS) and often generalization, the expansion of fear from the CS to similar, unlearned stimuli. However, how fear learning affects early sensory processing of learned and unlearned stimuli in relation to behavioral fear responses to these stimuli remains unclear. We subjected mice to a classical olfactory fear conditioning paradigm and used awake, in vivo calcium imaging to quantify learning-induced changes in glomerular odor responses, which constitutes the first site of olfactory processing in the brain. The results demonstrate that olfactory fear learning non-specifically enhances glomerular odor representations in a learning-dependent manner and increases representational similarity between the CS and non-conditioned odors. This mechanism may prime the system towards generalization of learned fear. Additionally, CS-specific enhancements remain even when associative learning is blocked; suggesting two separate mechanisms lead to enhanced glomerular responses following odor-shock pairings.

neuroscience↗

bioRxiv2016

Modeling HIV disease progression and transmission at population-level: The potential impact of modifying disease progression in HIV treatment programs

IntroductionMathematical models of HIV transmission that incorporate the dynamics of disease progression can estimate the potential impact of adjunctive strategies to antiretroviral therapy (ART) for HIV treatment and prevention. Suppressive treatment of HIV-positive persons co-infected with herpes simplex virus-2 (HSV-2) with valacyclovir, a medication directed against HSV-2, can lower HIV viral load, but the impact of valacyclovir on population HIV transmission has not been estimated.\n\nMethodsWe applied data on CD4 and viral load progression in ART-naive persons studied in two HIV clinical trials to a novel, discrete-time Markov model. We validated our disease progression estimates using data from a trial of home-based HIV counseling and testing in KwaZulu-Natal, South Africa. Finally, we applied our disease progression estimates to a dynamic transmission model estimating the impact of providing valacyclovir to ART-naive individuals to reduce onward transmission of HIV in three scenarios of different ART and valacyclovir population coverage. We assumed that valacyclovir reduced HIV viral load by 1.23 log copies/L, and that persons treated with valacyclovir initiated ART more rapidly when their CD4 fell below 500 due to improved retention in pre-ART care.\n\nResultsThe average duration of HIV infection following acute infection was 9.5 years. The duration of disease after acute infection and before reaching CD4 200 cells/L was 2.53 years longer for females than males. Relative to a baseline of community HIV testing and counseling and ART initiation at CD4 <=500 cells/L, valacyclovir with increased linkage to care resulted in 166,000 fewer HIV infections over ten years, with an incremental cost-effectiveness ratio (ICER) of $4,696 per HIV infection averted. The Test and Treat scenario with 70% ART coverage and no valacyclovir resulted in 202,000 fewer HIV infections at an ICER of $6,579.\n\nConclusionEven when compared with initiation of valacyclovir, a safe drug that reduces HIV viral load, universal treatment for HIV is the optimal strategy for averting new infections and increasing public health benefit. Universal HIV treatment should be pursued by all countries to most effectively and efficiently reduce the HIV burden.

epidemiology↗