New publication: Acoustic coordinated reset therapy for tinnitus with perceptually relevant frequency spacing and levels

The source of some symptoms for several chronic neurologic conditions is abnormal synchronous neuronal firing in a focal area of the brain, according to current theory. Abnormal synchronous neural activity has been associated with tinnitus (“ringing in the ears”), phantom limb pain, and several other chronic neural conditions such as symptoms in Parkinsons disease. Based on computational studies and neuroplasticity principles, coordinated reset neuromodulation therapy involves the delivery of sequential, low-level, short term signals that activate neural areas immediately adjacent to this focal spot to induce sustained, long-lasting desynchronization at the focal spot and subsequent reduction of symptoms. The neuromodulation signals can be applied either non-invasively (via a sensory system, eg) or invasively (via surgically implanted electrodes, eg). In the case of frequency-specific tonal tinnitus the abnormal focal spot is thought to be located in the auditory cortex within about a 35 mm strip of organized neurons that closely maps the strip of sensory tissue in the cochlea, systematically processing the frequency of the auditory sensory signal. For acoustic neuromodulation intervention, the focal source of the abnormal synchrony on the auditory cortex is identified by matching the pitch of the tinnitus to the frequency of an externally applied tone. The neuromodulation intervention then involves the sequential presentation of several sinusoidal signals with frequencies on either side of the tinnitus frequency for a short period intended to reduce or eliminate the tinnitus percept after the therapy. A proof of concept study in 63 patients with chronic, frequency-specific tonal tinnitus showed that neuromodulation treatment, delivered to the auditory system for ~5h/day for 12 weeks, resulted in substantial reduction in tinnitus loudness, annoyance and handicap compared to baseline with sustained effects up to 10 months in ~75% of the trial subjects. Changes in tinnitus-related neural connectivity as measured with high density EEG recordings also were observed. Similar effects also were observed in two additional clinical studies.

The neural area activated by neuromodulation signals can overlap with the neural area of the focal spot depending on a variety of factors. Known changes in spatial activation of auditory cortical areas are related to excitation and inhibition patterns, signal level and hearing loss. Auditory filters play a key role in tuning the sensory system and subsequently the spatial area of cortical neural activation. The area can be specified in a standard way using the concept of the equivalent rectangular bandwidth (ERB) that can be used to account for changes associated with signal level and magnitude of hearing loss. Though none of the previous computational 1D, 2D and 3D neural network modeling studies considered these factors, the activation areas of the cortical sites were symmetrical with identical overlap of adjacent activation sites. This strongly suggests that neuromodulation signals that enable symmetric activation with known overlaps of cortical sub-populations of neurons will be favorable for desynchronization.

The purpose of this article was to develop a more advanced, auditory filter-based theoretical basis for the selection of the acoustic neuromodulation signals that incorporates both a more perceptually relevant frequency scale relative to the frequency matched to the tinnitus pitch, as well as known changes associated with neuromodulation signal level and magnitude of sensorineural hearing loss at the frequency of the neuromodulation signal. Based on this theoretical approach we analyzed the neuromodulation signals used to date and designed optimized neuromodulation signal arrangements that can be tested experimentally.

The information in this study also can be used to optimize all neuromodulation interventions intended to desynchronize abnormally synchronized activity at a focal spot. For example, in the case of tinnitus, sensorineural hearing loss greater than about 55 dB HL at the signal frequency prevents the use of auditory signals. In these cases the patient may still benefit from neuromodulation intervention of specific cortical sites with transcranial focussed ultrasound to activate directly the neural areas of interest. Transcranial focussed ultrasound can be considered as a non-invasive alternative to the auditory system in the case of tinnitus and possibly other neurologic conditions as well.

Tass et al. 2019. Acoustic coordinated reset therapy for tinnitus with perceptually relevant frequency spacing and levels. Scientific Reports. (link to article)