Increased Synchrony and Bursting of Dorsal Cochlear Nucleus Fusiform Cells Correlate with Tinnitus

Wu, Calvin; Martel, David T.; Shore, Susan E.

doi:10.1523/jneurosci.3960-15.2016

Cited by 107 publications

(169 citation statements)

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“…Increased synchrony, bursting and spontaneous activity are established neural correlates of tinnitus (14). To determine whether dysregulated STDP contributes to tinnitus-related hypersynchrony, we induced tinnitus in guinea pigs using noise exposure, and assessed tinnitus using gap-prepulse inhibition of the acoustic startle (GPIAS) response.).…”

Section: Resultsmentioning

confidence: 99%

“…In animal models of tinnitus, increased synchrony has been identified in the DCN (14), inferior colliculus (25) and auditory cortex (26). These studies suggest that the tinnitus percept emerges from increased spontaneous synchrony amongst neurons in cortical and subcortical regions that contribute to perceptual binding (27).…”

Section: Discussionmentioning

confidence: 99%

“…Following noise exposure sufficient to temporarily elevate hearing thresholds, spontaneous activity and cross-neural synchrony of DCN output neurons, the fusiform cells, are increased in animals showing behavioral evidence of tinnitus. Animals without behavioral evidence of tinnitus do not show these neural correlates (14). Further, the tinnitus-related neural changes can occur even in the absence of permanent shifts in behavioral audiometric thresholds or electrophysiological measures of peripheral hearing status (14, 15).…”

Section: Introductionmentioning

confidence: 99%

“…Animals without behavioral evidence of tinnitus do not show these neural correlates (14). Further, the tinnitus-related neural changes can occur even in the absence of permanent shifts in behavioral audiometric thresholds or electrophysiological measures of peripheral hearing status (14, 15). …”

Section: Introductionmentioning

confidence: 99%

“…S1), which are also subjected to spike-timing-dependent synaptic modulation (17). Thus, increased LTP in the fusiform cell circuit could contribute to the hypersynchrony and increased spontaneous activity that are considered neural correlates of tinnitus (14). …”

Section: Introductionmentioning

confidence: 99%

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Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans

et al. 2018

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The dorsal cochlear nucleus is the first site of multisensory convergence in mammalian auditory pathways. Principal output neurons, the fusiform cells, integrate auditory-nerve inputs from the cochlea with somatosensory inputs from the head and neck. In previous work, we developed a guinea pig model of tinnitus produced by noise exposure and showed that the fusiform cells in these animals exhibited increased spontaneous activity and cross-unit synchrony, which are physiological correlates of tinnitus. Here, we delivered repeated bimodal auditory-somatosensory stimulation to the dorsal cochlear nucleus of guinea pigs with tinnitus, choosing a stimulus interval known to induce long-term depression (LTD). Twenty minutes per day of LTD-targeting bimodal (but not unimodal) stimulation reduced physiological and behavioral evidence of tinnitus in the guinea pigs after 25 days. Next, we applied the same bimodal treatment to 20 human subjects with tinnitus using a double-blinded, sham-controlled, crossover study. Twenty-eight days of LTD-targeted bimodal stimulation reduced tinnitus loudness and intrusiveness. Unimodal auditory stimulation did not deliver either benefit. Bimodal auditory-somatosensory stimulation that targets LTD in the dorsal cochlear nucleus may hold promise for suppressing chronic tinnitus, which reduces quality of life for millions of tinnitus sufferers worldwide.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans

et al. 2018

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Reversing Synchronized Brain Circuits Using Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts

et al. 2023

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ImportanceAnimal models have shown altered dorsal cochlear nucleus circuitry in animals that develop tinnitus; however, precise treatment using bisensory (auditory and somatosensory) stimuli can reverse altered neural patterns and lessen tinnitus.ObjectiveTo confirm and extend the findings of a pilot study, which suggested an increased efficacy of bisensory stimulation, to a clinical trial with a greater duration and greater number of participants.Design, Setting, and ParticipantsThis double-blind, crossover, single-center randomized clinical trial was conducted from March 2019, with a 3-month follow-up per participant ending in July 2022. Eligible adults were recruited from the University of Michigan Health System in Ann Arbor, Michigan. Eligibility criteria included bothersome tinnitus (Tinnitus Functional Index [TFI] score, ≥17 points), somatic tinnitus, normal to moderate hearing loss, and no other tinnitus treatments in the 6 months prior to the trial. Included participants were randomized to either treatment group 1, which received active (bisensory) treatment, or group 2, which received the control (auditory-only) treatment. Results were analyzed using intent-to-treat (ITT) and per protocol (PP) populations.InterventionPrecisely timed bisensory (combined auditory and somatosensory) treatment was delivered through a portable, custom, take-home device that was provided to each participant for daily, at-home treatments. Group 1 participants received 30 minutes per day of the bisensory treatment for 6 weeks, followed by a 6-week washout phase, and then 30 minutes per day of the auditory-only treatment followed by a second 6-week washout phase. Group 2 participants received the auditory-only treatment first, followed by a washout phase, and then the bisensory treatment followed by a second washout phase.Main Outcomes and MeasuresPrimary end points were changes in TFI score and tinnitus loudness level from baseline through week 6 and week 12.ResultsOf 337 screened individuals, 99 (mean [SD] age, 47 [12.7] years; 59 males [60%]; 85 with non-Hispanic White [86%] race and ethnicity) were enrolled into the study and randomized to treatment group 1 (n = 49) or group 2 (n = 50). The active but not the control treatment resulted in clinically significant decreases in TFI scores at week 6 of phase 1 (ITT population: –12.0 [95% CI, –16.9 to –7.9] points; P &lt; .001; PP population: –13.2 [95% CI, –16.0 to –10.5] points; P &lt; .001). Decreases in tinnitus loudness level were greater than 6 dB sensation level (SL; &gt;half as loud) at week 6 for the bisensory treatment group, with little effect for the auditory-only treatment control group at week 6 of phase 1 (ITT population: –5.8 [95% CI, –9.5 to –2.2] dB; P = .08; PP population: –7.2 [95% CI, –11.4 to –3.1] dB; P = .03), and up to 11 dB SL at week 12 of phase 2 (ITT population: –10.9 [95% CI, –15.2 to –6.5] dB; P = .001; PP population: –14.1 [95% CI, –18.4 to –9.8] dB; P &lt; .001). Decreased tinnitus loudness level and TFI scores extended into the washout phase, indicating a prolonged treatment effect.Conclusions and RelevanceThis trial found that precisely timed bisensory treatment using stimuli and timing developed in a validated animal model was effective for adults with somatic tinnitus. Prolonged reduction in tinnitus symptoms can result from using an extended treatment duration.Trial RegistrationClinicalTrials.gov Identifier: NCT03621735

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Unintended Consequences of White Noise Therapy for Tinnitus—Otolaryngology's Cobra Effect

Attarha

Bigelow

Merzenich

2018

JAMA Otolaryngol Head Neck Surg

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Increased Synchrony and Bursting of Dorsal Cochlear Nucleus Fusiform Cells Correlate with Tinnitus

Cited by 107 publications

References 40 publications

Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans

Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans

Reversing Synchronized Brain Circuits Using Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts

Unintended Consequences of White Noise Therapy for Tinnitus—Otolaryngology's Cobra Effect

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