A new concept for noninvasive tinnitus treatment utilizing multimodal pathways

Abstract

-Current noninvasive treatments for tinnitus have shown mixed results. There have been encouraging developments in using invasive brain or vagal nerve stimulation to modulate neural populations driving the tinnitus percept. However, these invasive treatments can only be used in a small patient population with severe conditions. In this preliminary study, we present a new treatment option we call Multimodal Synchronization Therapy (MST), which attempts to achieve synchronized and localized brain activation without invasive neural stimulation. MST combines multiple sensory, motor, limbic, and cognitive inputs to elicit activation of multimodal neurons to potentially modulate specific neurons driving the tinnitus percept. We present preliminary data in a guinea pig model showing activation of somatosensory and auditory pathways to alter neural activity within the inferior colliculus, a multimodal integration region that has shown pathological changes in animals and patients with tinnitus. Electrical stimulation of different body locations induced excitatory responses in the inferior colliculus, eliciting responses in up to 41% of all recording sites for a given somatic site. Paired somatic and acoustic stimulation resulted in enhanced or suppressed acoustic-driven neural activity in the inferior colliculus that varied depending on stimulation and recording location. Similar modulation effects were observed in the auditory cortex, which may relate to changes in auditory perception. Further studies need to incorporate multiple multimodal pathways and must also confirm that MST can suppress the abnormal neural patterns that directly drive the tinnitus percept.

An Investigation of Feasibility and Safety of Bi-Modal Stimulation for the Treatment of Tinnitus: An Open-Label Pilot Study

“…Bi‐modal stimulation is emerging as a compelling approach to tinnitus treatment . De Ridder et al paired tones with VNS in 10 tinnitus patients who were previously unresponsive to other treatments.…”

Different bimodal neuromodulation settings reduce tinnitus symptoms in a large randomized trial

“…The overall ndings from this TENT-A2 study indicate that a diverse range of electrical and sound stimulus combinations can signi cantly improve tinnitus symptoms and aligns with ndings from previous animal and human research on bimodal neuromodulation. [7][8][9][10][11][12][13][14][15][16] Animal studies have shown that sound stimulation paired with electrical stimulation of different body locations (or related nerves), such as the face, neck, ear, tongue, back and limbs can all drive extensive neural plasticity across the auditory pathway, including in the cochlear nucleus, inferior colliculus and auditory cortex. 7,8,10,13−16 Both pure tone bursts and wideband noise bursts can be effective at driving signi cant auditory plasticity with bimodal neuromodulation.…”

“…5,6 Encouragingly, there has been a recent convergence of ndings across multiple animal and human studies demonstrating that bimodal neuromodulation combining sound with electrical stimulation of peripheral nerves, including vagus, trigeminal and other somatosensory nerves, can drive neural plasticity relevant for tinnitus treatment and signi cantly improve tinnitus symptoms. [7][8][9][10][11][12][13][14][15][16] Previous animal studies have shown that bimodal stimulation combining electrical body stimulation combined with pure tones or wideband noise can alter brain activity within auditory regions associated with tinnitus. 7,8,13−15 These studies demonstrated that electrical stimulation of the vagus or trigeminal nerves or the surface of different body regions in animals (e.g., tongue, face, neck and ear) can alter brain patterns relevant for tinnitus treatment and reduce tinnitus symptom severity in human patients.…”

Tinnitus Treatment Using Noninvasive and Minimally Invasive Electric Stimulation: Experimental Design and Feasibility

“…At present, cochlear implantation is not applicable to tinnitus sufferers with normal hearing. The present strategy can be combined with other forms of treatment such as cognitive training and coordinated stimulation to produce a long-lasting effect and eventually find a cure for tinnitus (Cima et al., 2012; Engineer et al., 2011; Gloeckner, Smith, Markovitz, & Lim, 2013; Marks et al., 2018; Tass, Adamchic, Freund, von Stackelberg, & Hauptmann, 2012).…”