Neuroscience
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Debilitating perceptual disorders including tinnitus, hyperacusis, phantom limb pain and visual release hallucinations may reflect aberrant patterns of neural activity in central sensory pathways following a loss of peripheral sensory input. Here, we explore short- and long-term changes in gene expression that may contribute to hyperexcitability following a sudden, profound loss of auditory input from one ear. We used fluorescence in situ hybridization to quantify mRNA levels for genes encoding AMPA and GABAA receptor subunits (Gria2 and Gabra1, respectively) in single neurons from the inferior colliculus (IC) and auditory cortex (ACtx). ⋯ By contrast to the opposing, synergistic shifts in Gria2 and Gabra1 observed 30 days after hearing loss, we found that transcription levels for both genes were equivalently reduced after 5 days of hearing loss, producing no net change in the excitatory/inhibitory transcriptional balance. Opposing transcriptional shifts in AMPA and GABA receptor genes that emerge several weeks after a peripheral insult could promote both sensitization and disinhibition to support a homeostatic recovery of neural activity following auditory deprivation. Imprecise transcriptional changes could also drive the system toward perceptual hypersensitivity, degraded temporal processing and the irrepressible perception of non-existent environmental stimuli, a trio of perceptual impairments that often accompany chronic sensory deprivation.
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For successful future therapeutic strategies for tinnitus and hyperacusis, a subcategorization of both conditions on the basis of differentiated neural correlates would be of invaluable advantage. In the present study, we used our refined operant conditioning animal model to divide equally noise-exposed rats into groups with either tinnitus or hyperacusis, with neither condition, or with both conditions co-occurring simultaneously. Using click stimulus and noise burst-evoked Auditory Brainstem Responses (ABR) and Distortion Product Otoacoustic Emissions, no hearing threshold difference was observed between any of the groups. ⋯ Preliminary studies, aimed at establishing comparable non-invasive objective tools for identifying tinnitus in humans and animals, confirmed reduced central gain and delayed response latency in human and animals. Moreover, the first ever resting state functional Magnetic Resonance Imaging (rs-fMRI) analyses comparing humans and rats with and without tinnitus showed reduced rs-fMRI activities in the auditory cortex in both patients and animals with tinnitus. These findings encourage further efforts to establish non-invasive diagnostic tools that can be used in humans and animals alike and give hope for differentiated classification of tinnitus and hyperacusis.
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Previous studies suggest that envelope-following responses (EFRs) reveal important differences in temporal coding fidelity amongst listeners who have normal hearing thresholds, consistent with these listeners differing in the degree to which they suffer from cochlear synaptopathy. Like conventional hearing loss, the severity of cochlear synaptopathy may vary along the cochlea. A number of earlier studies have suggested methods for estimating EFRs driven by specific frequency regions of the cochlea, which would allow synaptopathy to be estimated as a function of cochlear place. ⋯ Other results suggested that while off-frequency contributions to EFRs driven by narrowband signals (due to spread of excitation) can add destructively to the on frequency response, these interactions were small compared to EFR magnitude. Overall, our results point to the utility of using multi-band complex tone stimuli to estimate the profile of temporal coding fidelity, and thus the degree of synaptopathy, as a function of cochlear place. This article is part of a Special Issue entitled: Hearing Loss, Tinnitus, Hyperacusis, Central Gain.
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The superior temporal sulcus (STS) encompasses a complex set of regions involved in a wide range of cognitive functions. To understand its functional properties, neuromodulation approaches such brain stimulation or neurofeedback can be used. We investigated whether the posterior STS (pSTS), a core region in the face perception and imagery network, could be specifically identified based on the presence of dynamic facial expressions (and not just on simple motion or static face signals), and probed with neurofeedback. ⋯ Our results provide evidence that a facial expression-selective cluster in pSTS can be identified and may represent a suitable target for neurofeedback approaches, aiming at social and emotional cognition. These findings highlight the presence of a highly selective region in STS encoding dynamic aspects of facial expressions. Future studies should elucidate its role as a mechanistic target for neurofeedback strategies in clinical disorders of social cognition such as autism.