Low-intensity repetitive transcranial magnetic stimulation over prefrontal cortex in an animal model alters activity in the auditory thalamus but does not affect behavioural measures of tinnitus

Mulders, Wilhelmina; Leggett, Kerry; Mendis, V.; Tarawneh, Hadeel Y.; Wong, Joshua K.; Rodger, Jennifer

doi:10.1007/s00221-018-05468-w

Cited by 10 publications

(17 citation statements)

References 78 publications

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“…Twelve of the 19 animals developed a GPIAS deficit at 8 kHz, four animals at 14 kHz, and three animals at both background frequencies. This is in line with our previous studies showing that the GPIAS deficit can occur at either or both frequencies (Mulders et al, 2014a(Mulders et al, , 2016(Mulders et al, , 2019Leggett et al, 2018). The background noise/prepulse center frequencies used for GPIAS and PPI (8 and 14 kHz) were selected as these frequencies are just below the AT frequency in an audiogram region without threshold loss (8 kHz) and in a region just above the AT frequency showing threshold loss (14 kHz).…”

Section: Behavioral Tests For Tinnitussupporting

confidence: 93%

“…Detailed descriptions of behavioral testing for tinnitus (Robertson et al, 2013;Mulders et al, 2014aMulders et al, , 2016Leggett et al, 2018); AT surgery (Mulders and Robertson, 2009;Mulders et al, , 2014aVogler et al, 2011;Robertson et al, 2013); electrophysiological recordings in MGN including burst firing analysis (Barry et al, 2019;Mulders et al, 2019); and immunohistochemistry with associated quantitative analysis to determine densities of calcium-binding neurons in PFC (Mulders et al, 2019) have been described in previous papers from our laboratory and will be described only in brief in the next sections.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

“…Excitation of PFC was hypothesized to have inhibitory effects on thalamic and therefore cortical activity, and in this way, attenuate tinnitus. In addition, we investigated the effects of rTMS on PFC, through quantitative immunohistochemical analysis of calcium binding proteins, as studies have shown changes in these proteins following rTMS treatment (Benali et al, 2011;Hoppenrath and Funke, 2013;Volz et al, 2013;Labedi et al, 2014;Mix et al, 2014;Mulders et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

et al. 2021

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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.

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Section: Behavioral Tests For Tinnitussupporting

confidence: 93%

Section: Animals and Experimental Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

et al. 2021

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“…Conceivably, variations in the amount of increased inhibition of PCF on MGN could play a role in the individual variation in susceptibility to tinnitus development [55]. However, most animal models using similar cochlear trauma show behavioural evidence of tinnitus becoming apparent only after at least 4 to 6 weeks [56][57][58][59] and the present results were obtained only two weeks after cochlear trauma. Furthermore, we did not investigate the presence of tinnitus in this study.…”

Section: Discussionmentioning

confidence: 44%

Changes in Prefrontal Cortex–Thalamic Circuitry after Acoustic Trauma

2021

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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.

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“…During sleep, physiological changes occur in brain and body functions [11]. However, the accessory auditory system functions during sleep, which allows for the sound of music to exert effects on the subcortical areas and limbic system.…”

Section: Introductionmentioning

confidence: 99%

Individualized Treatment of Tinnitus during Sleep Using Combined Tinnitus Signal and Music

Deni̇z

Bayazıt

Sarac

2020

ORL

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Introduction: Tinnitus is a widely seen otological symptom that interferes with daily activities and causes discomfort. Tinnitus treatments can be classified into 4 main groups: pharmacological treatments, cognitive and behavioral therapy, psychological treatments, and combined treatment approaches made up of at least 2 of these 3 treatment methods. Objective: The aim of this study was to assess whether it would be possible to develop an individualized treatment method of tinnitus by application of a combined tinnitus signal and music during sleep. Methods: Forty-three ears of 30 patients who had subjective tinnitus were included. The patients were evaluated using Tinnitus Handicap Inventory, Visual Analogue Scale, and Beck Depression Inventory. The psychoacoustic parameters of tinnitus, such as tinnitus frequency and loudness, and minimal masking levels, were determined. The patients were asked to select musical melodies that they liked. The tinnitus frequency of each patient was taken as the central frequency according to ANSI 2004. All sound files were prepared as stereo channels, with 16-bit resolution and 44,100 Hz sampling rate. The root mean square power value of the music and the band noise’s average root mean square power value were equalized with the “Amplification” command, and 70% of the music and 30% of wide/narrow-band noise were mixed as a stereo channel by the “Mix Paste” command. The patients were instructed to listen to that individualized music/narrow-band noise (tinnitus signal) for 2 h during sleep for a duration of 6 months. Results: Tinnitus frequencies of the patients measured prior to treatment and at the second, fourth, and sixth months of follow-up were not significantly different. A statistically significant decrease was seen in tinnitus loudness, minimal masking levels, and residual inhibition during the follow-up. Tinnitus Handicap Inventory scores decreased significantly during follow-up, and the number of patients who complained of tinnitus decreased (p < 0.05). The Visual Analogue Scale scores significantly decreased during follow-up (p < 0.05). Beck Depression Inventory scores decreased significantly during follow-up (p < 0.05). Conclusion: Stimulation of the auditory and limbic systems during sleep by the tinnitus signal combined with individualized musical melodies seems an alternative, effective, and cheap method in the treatment of tinnitus.

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Low-intensity repetitive transcranial magnetic stimulation over prefrontal cortex in an animal model alters activity in the auditory thalamus but does not affect behavioural measures of tinnitus

Cited by 10 publications

References 78 publications

Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

Changes in Prefrontal Cortex–Thalamic Circuitry after Acoustic Trauma

Individualized Treatment of Tinnitus during Sleep Using Combined Tinnitus Signal and Music

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