Biology subjects

Tollin, D.

Publications and source records attributed to Tollin, D..

4 recordsLinked to original sources

bioRxiv2024

Computational model for synthesizing auditory brainstem responses to assess neuronal alterations in aging and autistic animal models

PurposeThe auditory brainstem response (ABR) is a widely used objective electrophysiology measure for non-invasively assessing auditory function and neural activity in the auditory brainstem, but its ability to reflect detailed neuronal processing is limited due to the averaging nature of the electroencephalogram-type recordings. MethodThis study addresses this limitation by developing a computational model of the auditory brainstem which is capable of synthesizing ABR traces based on a large, population scale neural extrapolation of a spiking neuronal network of auditory brainstem circuitry. The model was able to recapitulate alterations in ABR waveform morphology that have been shown to be present in two medical conditions: animal models of autism and aging. Moreover, in both of these conditions, these ABR alterations are caused by known distinct changes in auditory brainstem physiology, and the model could recapitulate these changes. ResultsIn the autism model, the simulation revealed myelin deficits and hyperexcitability, which caused a decreased wave III amplitude and a prolonged wave III-V interval, consistent with experimentally recorded ABRs in Fmr1-KO mice. For the aging condition, the model recapitulated ABRs recorded in aged gerbils and indicated a reduction in activity in the medial nucleus of the trapezoid body (MNTB), a finding validated by confocal imaging data. ConclusionThese results demonstrate not only the models accuracy but also its capability of linking features of ABR morphology to underlying neuronal properties and suggesting follow-up physiological experiments.

neuroscience↗

bioRxiv2024

Age-related myelin deficits in the auditory brain stem contribute to cocktail party-deficits

Age-related hearing loss consists of both peripheral and central components and is an increasing global health concern. While peripheral hearing loss is well understood, central hearing loss-- age-related changes in the central auditory pathways resulting in a listeners inability to process sound correctly --remains poorly understood. In this study, we focus on the pathway from the cochlear nucleus to the medial nucleus of the trapezoid body (MNTB), which depends on heavily myelinated axons for microsecond-level temporal precision required for sound localization. Using a combination of auditory brainstem response recordings (ABR), advanced light and electron microscopy, and behavioral testing with prepulse inhibition of the acoustic startle response (PPI) we identified a correlation between oligodendrocyte loss, abnormal myelination in MNTB afferents, altered ABR wave III morphology indicating MNTB dysfunction, and deficits in spatial hearing behaviors in aging Mongolian gerbils. These findings provide a mechanistic explanation of how demyelination contributes to age-related dysfunction in the auditory brainstems sound localization pathway.

neuroscience↗

bioRxiv2024

Degradation in Binaural and Spatial Hearing and Auditory Temporal Processing Abilities as a Function of Aging

ObjectivesSensorineural hearing loss is common with advancing age, but even with normal or near-normal hearing in older persons, performance deficits are often seen for suprathreshold listening tasks such as understanding speech in background noise or localizing sound direction. This suggests there is also a more central source of the problem. Objectives of this study were to examine as a function of age (young adult to septuagenarian) performance on: 1) a spatial acuity task examining localization ability, and a spatial speech-in-noise (SSIN) recognition task, both measured in a hemi-anechoic sound field using a circular horizontal-plane loudspeaker array, and 2) a suprathreshold auditory temporal processing task and a spectro-temporal processing task, both measured under headphones. Further, we examined any correlations between age, hearing thresholds including extended high frequency (EHF: >8000 Hz), and these measures. DesignSubjects were 48 adults, aged 21 to 78, with either normal hearing or only a mild sensorineural hearing loss through 4000 Hz. The localization task measured minimum audible angle (MAA) for 500 and 4000 Hz 1/3rd octave narrowband noise (NBN) in diffuse background noise for both an on-axis (reference source 0{degrees}) and off-axis (reference source 45{degrees}) listening condition at signal-to-noise ratios (SNRs) of -3, -6, -9, and -12 dB. SSIN testing was also completed for key word recognition in sentences in multi-talker babble noise; specifically, the separation between speech and noise loudspeakers was adaptively varied to determine the difference needed for 40% and 80% correct performance levels. Finally, auditory temporal processing ability was examined using the Temporal Fine Structure (TFS) test, and the Spectro-Temporal Modulation (STM) test. ResultsSpatial acuity was poorer (larger MAAs) in older compared to younger subjects, particularly in the more adverse listening conditions (off-axis, and poorer SNRs). The SSIN data also showed declining mean performance with age at both criterion levels, emerging in the middle age group (> 40 years), but was not correlated with standard audiometric hearing thresholds. Decreased performance on the TFS and STM tasks was dependent on age, emerging only in the older (> 60 years) and middle (>40 years) age groups, respectively; neither was dependent on hearing thresholds. Results of multiple regression analyses suggest that SSIN recognition scales with the ability of the subjects to use both low-frequency binaural temporal fine structure as well as higher-frequency binaural envelope cues, both of which are impacted by aging but not necessarily audiometric hearing thresholds. Finally, EHF range hearing thresholds significantly decreased with age, but performance on tasks remained significantly correlated with age when controlled for EHF hearing. ConclusionsParticularly for more adverse listening conditions, age-related deficits, but not hearing-threshold-related deficits, were found on both of the spatial hearing tasks and in temporal and spectro-temporal processing abilities. It may be that deficits in temporal processing ability contribute to poorer spatial hearing performance in older subjects due to inaccurate coding of binaural/interaural timing information sent from the periphery to the binaural brainstem. In addition, EHF hearing loss may be a coexisting factor in the reduced performance seen in older subjects.

neuroscience↗

bioRxiv2023

Time Tiling of Learned Stimulus-Based Decision Making in Dorsal CA1 in the Hippocampus

Sequential neural dynamics encoded by "time cells" play a crucial role in hippocampal function. However, the role of hippocampal sequential neural dynamics in associative learning is an open question. In this manuscript, we used two-photon Ca2+ imaging of dorsal CA1 pyramidal neurons in head-fixed mice performing a go-no-go associative learning task. We found that pyramidal cells responded differentially to the rewarded or unrewarded stimuli. The stimuli were decoded accurately from the activity of the neuronal ensemble, and accuracy increased substantially as the animal learned to differentiate the stimuli. Decoding the stimulus from individual pyramidal cells that responded differentially revealed that decision-making took place at discrete times after stimulus presentation. Lick prediction decoded from the ensemble activity of cells in dCA1 correlated linearly with lick behavior indicating that sequential activity of pyramidal cells in dCA1 constitutes a temporal memory map used for decision-making in associative learning.

neuroscience↗