ORCID Profile
0000-0002-1601-0997
Current Organisations
University of Western Australia
,
Ear Science Institute Australia
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Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.HEARES.2019.05.001
Abstract: Tinnitus is an abnormal phantom perception associated with cochlear trauma, and is thought to cause changes in the rates and patterns of firing neurons in the central auditory pathway. Recent studies have suggested a key role for the auditory thalamus, the medial geniculate nucleus (MGN), in the generation of tinnitus as it may serve a gating function for information en route to cortex. Dysfunctional gating would lead to abnormal activity reaching cortex and hence inappropriate perception, tinnitus, would occur. In this study we compared spontaneous MGN firing rates and burst firing parameters in Wistar rats with and without behavioural evidence of tinnitus following an acoustic trauma. Data were also compared with animals subjected to sham surgery and at an early time-point (2 weeks) after acoustic trauma. Acoustic trauma resulted in a temporary but not a permanent threshold loss and no differences were found in spontaneous firing rate between any of the groups. However, acoustic trauma, whether resulting in tinnitus or not, was accompanied by a significant decrease in the percentage of neurons showing burst firing. In bursting neurons, the number of spikes occurring in a burst and the number of burst per minutes was also significantly reduced compared to the sham group. Our results show that in our rat model without permanent threshold loss, elevated spontaneous firing rates are not associated with acoustic trauma and/or tinnitus and that burst firing parameters are associated with acoustic trauma but are not a neural signature for tinnitus.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.NEUROSCIENCE.2015.09.008
Abstract: Dysfunctional sensory gating has been proposed to result in the generation of phantom perceptions. In agreement, it has been recently suggested that tinnitus, a phantom perception of sound commonly associated with hearing loss, is the result of a breakdown of circuitry involving the limbic system and the medial geniculate nucleus (MGN) of the thalamus. In humans with tinnitus, structural changes and abnormal activity have been found to occur in the auditory pathway as well as parts of the limbic system such as the nucleus accumbens (NAc). However, at present, no studies have been conducted on the influence of the NAc on the MGN. We investigated the functional connectivity between the NAc and MGN single neurons. Bipolar electrical stimulation was delivered to the NAc while recording single neuron activity in MGN in anesthetized Wistar rats. Histological analysis was used to confirm placement of electrodes. NAc electrical stimulation generally decreased spontaneous firing rates in MGN neurons and, in a limited number of neurons, caused an increase in firing rate. This suggests that NAc can modulate the activity of auditory neurons in the MGN and may play a role in the development of tinnitus.
Publisher: Elsevier BV
Date: 04-2021
DOI: 10.1016/J.HEARES.2021.108190
Abstract: The mechanism of tinnitus, the perception of sound in the absence of acoustic stimulation, remains as yet unknown. It has been proposed that tinnitus is caused by altered spontaneous activity in the auditory pathway following cochlear damage in combination with inadequate gating at the level of the auditory thalamus, the medial geniculate nucleus (MGN). To investigate this further we made electrophysiological recordings in MGN of guinea pigs (n = 9) with and without tinnitus after acoustic trauma (continuous loud tone at 10 kHz, 124 dB SPL for 2 h). Parameters of interest were spontaneous tonic and burst firing. After acoustic trauma, 5 out of 9 guinea pigs developed signs of tinnitus as determined by the gap prepulse inhibition of acoustic startle. Spontaneous firing rates were significantly increased in the tinnitus animals as compared to the non-tinnitus animals and this change was specific to pure-tone responsive MGN neurons. However, burst firing parameters, including number of bursts per minute, burst duration, number of spikes in each burst, and percentage of spikes occurring in a burst, were not different between tinnitus and non-tinnitus animals. In addition, our data showed a strong dependence of spontaneous firing rates with heart rate, which implies that monitoring physiological status in animals is pertinent to obtaining reliable data when recording at higher levels of the auditory pathway. Our results suggest that increases in the tonic spontaneous fining rate of pure-tone responsive MGN neurons but not changes in burst firing parameters, are a robust neural signature of tinnitus in anaesthetised animals.
Publisher: Frontiers Media SA
Date: 22-07-2021
DOI: 10.3389/FNINS.2021.693935
Abstract: Tinnitus, a phantom auditory perception that can seriously affect quality of life, is generally triggered by cochlear trauma and associated with aberrant activity throughout the auditory pathways, often referred to as hyperactivity. Studies suggest that non-auditory structures, such as prefrontal cortex (PFC), may be involved in tinnitus generation, by affecting sensory gating in auditory thalamus, allowing hyperactivity to reach the cortex and lead to perception. Indeed, human studies have shown that repetitive transcranial magnetic stimulation (rTMS) of PFC can alleviate tinnitus. The current study investigated whether this therapeutic effect is achieved through inhibition of thalamic hyperactivity, comparing effects of two common clinical rTMS protocols with sham treatment, in a guinea pig tinnitus model. Animals underwent acoustic trauma and once tinnitus developed were treated with either intermittent theta burst stimulation (iTBS), 20 Hz rTMS, or sham rTMS (10 days, 10 min/day weekdays only). Tinnitus was reassessed and extracellular recordings of spontaneous tonic and burst firing rates in auditory thalamus made. To verify effects in PFC, densities of neurons positive for calcium-binding proteins, calbindin and parvalbumin, were investigated using immunohistochemistry. Both rTMS protocols significantly reduced tinnitus compared to sham. However, spontaneous tonic firing decreased following 20 Hz stimulation and increased following iTBS in auditory thalamus. Burst rate was significantly different between 20 Hz and iTBS stimulation, and burst duration was increased only after 20 Hz treatment. Density of calbindin, but not parvalbumin positive neurons, was significantly increased in the most dorsal region of PFC indicating that rTMS directly affected PFC. Our results support the involvement of PFC in tinnitus modulation, and the therapeutic benefit of rTMS on PFC in treating tinnitus, but indicate this is not achieved solely by suppression of thalamic hyperactivity.
Publisher: Public Library of Science (PLoS)
Date: 16-05-2014
Publisher: Frontiers Media SA
Date: 03-2022
DOI: 10.3389/FNSYN.2022.840368
Abstract: Sensory gating is the process whereby irrelevant sensory stimuli are inhibited on their way to higher cortical areas, allowing for focus on salient information. Sensory gating circuitry includes the thalamus as well as several cortical regions including the prefrontal cortex (PFC). Defective sensory gating has been implicated in a range of neurological disorders, including tinnitus, a phantom auditory perception strongly associated with cochlear trauma. Recently, we have shown in rats that functional connectivity between PFC and auditory thalamus, i.e., the medial geniculate nucleus (MGN), changes following cochlear trauma, showing an increased inhibitory effect from PFC activation on the spontaneous firing rate of MGN neurons. In this study, we further investigated this phenomenon using a guinea pig model, in order to demonstrate the validity of our finding beyond a single species and extend data to include data on sound evoked responses. Effects of PFC electrical stimulation on spontaneous and sound-evoked activity of single neurons in MGN were recorded in anaesthetised guinea pigs with normal hearing or hearing loss 2 weeks after acoustic trauma. No effect, inhibition and excitation were observed following PFC stimulation. The proportions of these effects were not different in animals with normal hearing and hearing loss but the magnitude of effect was. Indeed, hearing loss significantly increased the magnitude of inhibition for sound evoked responses, but not for spontaneous activity. The findings support previous observations that PFC can modulate MGN activity and that functional changes occur within this pathway after cochlear trauma. These data suggest hearing loss can alter sensory gating which may be a contributing factor toward tinnitus development.
Publisher: MDPI AG
Date: 14-01-2021
DOI: 10.3390/BIOMEDICINES9010077
Abstract: In the adult auditory system, loss of input resulting from peripheral deafferentation is well known to lead to plasticity in the central nervous system, manifested as reorganization of cortical maps and altered activity throughout the central auditory pathways. The auditory system also has strong afferent and efferent connections with cortico-limbic circuitry including the prefrontal cortex and the question arises whether this circuitry is also affected by loss of peripheral input. Recent studies in our laboratory showed that PFC activation can modulate activity of the auditory thalamus or medial geniculate nucleus (MGN) in normal hearing rats. In addition, we have shown in rats that cochlear trauma resulted in altered spontaneous burst firing in MGN. However, whether the PFC influence on MGN is changed after cochlear trauma is unknown. We investigated the effects of electrical stimulation of PFC on single neuron activity in the MGN in anaesthetized Wistar rats 2 weeks after acoustic trauma or sham surgery. Electrical stimulation of PFC showed a variety of effects in MGN neurons both in sham and acoustic trauma groups but inhibitory responses were significantly larger in the acoustic trauma animals. These results suggest an alteration in functional connectivity between PFC and MGN after cochlear trauma. This change may be a compensatory mechanism increasing sensory gating after the development of altered spontaneous activity in MGN, to prevent altered activity reaching the cortex and conscious perception.
Publisher: MDPI AG
Date: 18-08-2022
Abstract: The auditory phantom sensation of tinnitus is associated with neural hyperactivity. Modulating this hyperactivity using repetitive transcranial magnetic stimulation (rTMS) has shown beneficial effects in human studies. Previously, we investigated rTMS in a tinnitus animal model and showed that rTMS over prefrontal cortex (PFC) attenuated tinnitus soon after treatment, likely via indirect effects on auditory pathways. Here, we explored the duration of these beneficial effects. Acoustic trauma was used to induce hearing loss and tinnitus in guinea pigs. Once tinnitus developed, high-frequency (20 Hz), high-intensity rTMS was applied over PFC for two weeks (weekdays only 10 min/day). Behavioral signs of tinnitus were monitored for 6 weeks after treatment ended. Tinnitus developed in 77% of animals between 13 and 60 days post-trauma. rTMS treatment significantly reduced the signs of tinnitus at 1 week on a group level, but in idual responses varied greatly at week 2 until week 6. Three (33%) of the animals showed the attenuation of tinnitus for the full 6 weeks, 45% for 1–4 weeks and 22% were non-responders. This study provides further support for the efficacy of high-frequency repetitive stimulation over the PFC as a therapeutic tool for tinnitus, but also highlights in idual variation observed in human studies.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.HEARES.2017.07.002
Abstract: Phantom perceptions have been proposed to arise due to dysfunctional sensory gating at the level of the thalamus. Recently, it has been suggested that tinnitus, a phantom perception of sound, may arise from altered cortico-limbic circuitry and its connection with the auditory thalamus, the medial geniculate nucleus (MGN). Indeed, some elements of this cortico-limbic circuitry, such as the prefrontal cortex (PFC), as well as elements of the auditory pathway, have been shown to be altered in humans with tinnitus. However, the functional connectivity between PFC and MGN has not yet been explored. We therefore investigated the effects of activation of the PFC on neuronal activity in MGN in normal anaesthetized Wistar rats. Bipolar electrical stimulation was delivered to the PFC while recording single neuron activity in the MGN. The majority (81%) of MGN neurons s led showed a change in their spontaneous firing rate in response to electrical stimulation of the PFC. The effects observed varied greatly between neurons and included combinations of inhibitory and excitatory effects with a wide range of latencies. The effects were not dependent on acoustic response type or MGN sub ision. These data demonstrate that PFC activation can modulate MGN neuronal activity and this connection could potentially play a role in sensory gating of auditory signals.
No related grants have been discovered for Kristin Barry.