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- ItemEnsemble responses of auditory midbrain neurons in the cat to speech stimuli at different signal-to-noise ratios(Hearing Research, 2024-12-03) Anu Sabu; Dexter Irvine; David B Grayden; James FallonOriginally reserved for those who are profoundly deaf, cochlear implantation is now common for people with partial hearing loss, particularly when combined with a hearing aid. This combined intervention enhances speech comprehension and sound quality when compared to electrical stimulation alone, particularly in noisy environments, but the physiological basis for the benefits is not well understood. Our long-term aim is to elucidate the underlying physiological mechanisms of this improvement, and as a first step in this process, we have investigated in normal hearing cats, the degree to which the patterns of neural activity evoked in the inferior colliculus (IC) by speech sounds in various levels of noise allows discrimination between those sounds. Neuronal responses were recorded simultaneously from 32 sites across the tonotopic axis of the IC in anaesthetised normal hearing cats (n = 7). Speech sounds were presented at 20, 40 and 60 dB SPL in quiet and with increasing levels of additive noise (signal-to-noise ratios (SNRs) –20, –15, –10, –5, 0, +5, +10, +15, +20 dB). Neural discrimination was assessed using a Euclidean measure of distance between neural responses, resulting in a function reflecting speech sound differentiation across various SNRs. Responses of IC neurons reliably encoded the speech stimuli when presented in quiet, with optimal performance when an analysis bin-width of 5–10 ms was used. Discrimination thresholds did not depend on stimulus level and were best for shorter analysis binwidths. This study sheds light on how the auditory midbrain represents speech sounds and provides baseline data with which responses to electro-acoustic speech sounds in partially deafened animals can be compared.
- ItemMeasuring Speech Discrimination Ability in Sleeping Infants Using fNIRS-A Proof of Principle(Trends in Hearing, 2025) Onn Wah Lee; Demi Gao; Tommy Peng; Julia Wunderlich; Darren Mao; Gautam Balasubramanian; Colette M McKayThis study used functional near-infrared spectroscopy (fNIRS) to measure aspects of the speech discrimination ability of sleeping infants. We examined the morphology of the fNIRS response to three different speech contrasts, namely “Tea/Ba,”“Bee/ Ba,” and “Ga/Ba.” Sixteen infants aged between 3 and 13 months old were included in this study and their fNIRS data were recorded during natural sleep. The stimuli were presented using a nonsilence baseline paradigm, where repeated standard stimuli were presented between the novel stimuli blocks without any silence periods. The morphology of fNIRS responses varied between speech contrasts. The data were fit with a model in which the responses were the sum of two independent and concurrent response mechanisms that were derived from previously published fNIRS detection responses. These independent components were an oxyhemoglobin (HbO)-positive early-latency response and an HbO-negative late latency response, hypothesized to be related to an auditory canonical response and a brain arousal response, respectively. The goodness of fit of the model with the data was high with median goodness of fit of 81%. The data showed that both response components had later latency when the left ear was the test ear (p<.05) compared to the right ear and that the negative component, due to brain arousal, was smallest for the most subtle contrast, “Ga/Ba” (p=.003).
- ItemExtent of genetic and epigenetic factor reprogramming via a single viral vector construct in deaf adult mice(Hearing Research, 2024-12-20) Niliksha Gunewardene; Patrick Lam; Jiwei Song; Trung Nguyen; Shannon Mendez Ruiz; Raymond C B Wong; Andrew K Wise; Rachael T RichardsonIn the adult mammalian cochlea, hair cell loss is irreversible and causes deafness. The basic helix-loop transcription factor Atoh1 is essential for normal hair cell development in the embryonic ear. Over-expression of Atoh1 in the adult cochlea by gene therapy can convert supporting cells (cells that underlie hair cells) into a hair cell lineage. However, the regeneration outcomes can be inconsistent. Given that hair cell development is regulated by multiple signalling and transcriptional factors in a temporal and spatial manner, a more complex combinatorial approach targeting additional transcription factors may be required for efficient hair cell regeneration. There is evidence that epigenetic factors are responsible for the lack in regenerative capacity of the deaf adult cochlea. This study aimed to develop a combined gene therapy approach to reprogram both the genome and epigenome of supporting cells to improve the efficiency of hair cell regeneration. Adult Pou4f3-DTR mice were used in which the administration of diphtheria toxin was used to ablate hair cells whilst leaving supporting cells relatively intact. A single adeno-associated viral construct was used to express human Atoh1, Pou4f3 and short hairpin RNA against Kdm1a (regeneration gene therapy) at two weeks following partial or severe hair cell ablation. The average transduction of the inner supporting cells, as measured by the control AAV2.7m8-GFP vector in the deaf cochlea, was only 8 % while transduction in the outer sensory region was <1 %. At 4- and 6-weeks post-treatment the number of Myo+ hair cells in the control and regeneration gene therapy-treated mice were not significantly different. Of note, although both control and regeneration gene therapy treated cochleae contained supporting cells that co-expressed the hair cell marker Myo7a and the supporting cell marker Sox2, the regeneration gene therapy treated cochleae had significantly higher numbers of these cells (p < 0.05). Furthermore, among these treated cochleae, those that had more hair cell loss had a higher number of Myo7a positive supporting cells (R2=0.33, Pearson correlation analysis, p < 0.001). Overall, our results indicate that the adult cochlea possesses limited intrinsic spontaneous regenerative capacity, that can be further enhanced by genetic and epigenetic reprogramming.
- ItemThe Mindful Brain at Rest: Neural Oscillations and Aperiodic Activity in Experienced Meditators(bioRxiv, 2024-10-30) McQueen, Brittany; Mrphy, Oscar W; Fitzgerald, Paul B; Bailey, Neil WObjectives Previous research has demonstrated that mindfulness meditation is associated with a variety of benefits, including improved mental health. Researchers have suggested these benefits may be underpinned by differences in neural oscillations. However, previous studies measuring neural oscillations have not controlled for non-oscillatory neural activity, the power spectrum of which follows a 1/f distribution and contributes to power measurements within oscillation frequencies of interest. In this study, we applied recently developed methods to determine if past findings related to neural oscillations in meditation are present even after controlling for non-oscillatory 1/f activity. Methods 48 experienced meditators and 44 non-meditators provided resting electroencephalography (EEG) recordings. Whole scalp EEG comparisons (topographical ANOVAs) were used to test for differences between meditators and non-meditators in the distribution or global power of activity for theta, alpha, beta, and gamma oscillations, and for the 1/f components slope and intercept. Results Results indicated that meditators showed differences in theta, alpha, and gamma oscillatory power compared to non-meditators (all p < 0.05). Post-hoc testing suggested that the oscillatory differences were primarily driven by differences in the distribution of neural activity between meditators and non-meditators, rather than differences in the overall power across all scalp electrodes. Conclusion Our results suggest that experience with meditation is associated with higher oscillatory power and altered distributions of theta, alpha and gamma oscillations, even after controlling for non-oscillatory 1/f activity. Band-specific differences in oscillatory activity may be a mechanism through which meditation leads to neurophysiological benefits.
- ItemEditorial: Gastrointestinal autonomic disorders.(Frontiers in Neurology, 2024-09-30) Tustumi, Francisco; Ho, Vincent; Payne, Sophie Clementine; Carra, Rafael Bernhart