Thank you! Actually, with the device we have in mind, it will be fairly easy to translate to humans. At the end of the presentation, I showed a man wearing a Transcutaneous Electrical Nerve Stimulation (TENS) unit, which is a safe treatment for muscle/tendon pain today (I actually used one for sports rehab years ago). We could use a device similar to this to electrically stimulate the skin at low levels without inducing pain, which would accomplish the same effect as we did with the guinea pigs. The great thing about the discovery of somatotopy within the inferior colliculus is that we now believe we can target any subpopulation of neurons with the correct stimulation combination of different parts of the body. We could instruct the patient to apply TENS stimulators to many different body locations, and then develop a computer algorithm to test all of the different combinations of stimulation sites to target all of the possible pathogenic neural populations. The patient would simply record which combinations work and which do not, allowing us to have patient specificity with our safe device. Approval for this would not be difficult to obtain since TENS devices are already on the market.

We chose a guinea pig model because the auditory system of the guinea pig is similar to that of humans in functionality and in the range of audible frequencies. It is a well characterized and well accepted model in the field of auditory neuroscience, and it is a model that my lab has used for other studies in the past. Some labs use cats, but the audible frequency range is not as similar, and recording from the inferior colliculus of a cat can be tricky, requiring the surgeon to aspirate part of the cortex which could affect neural signals. Aspiration is not necessary for guinea pig recordings.

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Thank you! There is not yet any literature of this therapy, which is why it is so innovative. We recently found that different combinations of somatosensory stimulation can suppress acoustic driven neural activity in the auditory system, as well as spontaneous neural activity. We have also shown differential effects (i.e. some parameters causing suppression while others causing excitation). We recently had a conference paper accepted on this topic, and we are in the process of submitting a more detailed paper to a journal as well. This will be the first published work on the topic.

We use a Michigan probe for our recordings, with a site size of 177 square microns and a site spacing of 200 microns. While this does not allow us to identify an individual neuron, it does allow us to pinpoint a relatively small area where activity occurs. With regards to the therapy, this is a good enough resolution. No studies have confirmed that individual neurons cause tinnitus, but rather neural populations. Many researchers believe that it could be due to small subpopulations for many patients that have frequency specific tinnitus (where the perceived sound is of one frequency or of a small band of frequencies as opposed to broadband noise) since only a small population of neurons in each brain region of the auditory system would be dedicated to a small band of frequencies. It has been shown in many published studies that these Michigan probes are capable of identifying specific frequency lamina in the central nucleus of the inferior colliculus and in the auditory cortex with good enough resolution to segregate populations based on frequency, so we feel that these recordings are resolute enough to identify somatotopy for our purposes. This study is simply a proof of concept to show that we can target different areas of the auditory system by stimulating different parts of the body.

As for the neuroscience point of view, spatial resolution is a very good point. To be able to accurately map somatosensory inputs to the inferior colliclus at an even higher resolution would be an important addition to our work. It would be interesting to see if two neurons right next to each other behave in the same way, or if it truly is simply a matter of larger populations of neurons at work.

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Thanks for the reply. I thought some applications of reflex zone therapy and acupuncture might be examples. I think there are acupressure/acupuncture approaches for tinnitus, don’t know how effective those are, but it might merit referencing.

You are correct! Acupressure/acupuncture approaches have been used, and are still used today. The results are really hit or miss. We think that maybe the correct combination of body locations are not being addressed for patients that do not see positive results from acupuncture, which would support our claims. It’s certainly something that I think I will add to my poster for my next conference presentation in the Fall. Thanks for the suggestion!

Thank you! This concept is actually one of my specific aims for my thesis. We are currently working on identifying combinations of somatosensory stimulation sites with certain parameters that can induce plasticity in the auditory system. This work is not yet published, so I can’t comment on the exact method or specific parameters that we have used. What I can tell you is that preliminary data has shown suppression of acoustic driven and spontaneous neural activity that lasts for over 1 hours after 2-3 minutes of a stimulation paradigm in the guinea pig model. We haven’t optimized this yet, so I can’t say if we will ever find a combination that will induce permanent plasticity. However, a realistic goal is to find a way to induce plasticity for an entire day. 2-3 minutes of stimulation is quick and easy, and if patients only have to do this once each morning, it would be a huge breakthrough for those who are severely affected by tinnitus. The device we have in mind involves stimulators similar to a Transcutaneous Electrical Nerve Stimulation (TENS) unit, which was shown at the end of my presentation. This device is very user friendly, and takes less than a minute to put on and take off. If the therapy works, less than five minutes each morning could be enough to cure tinnitus.

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Thank you! This is actually the next step for my project. We recently had a conference paper accepted on this topic. Preliminary data shows that different combinations of stimulation sites with different time delays can cause different amounts of suppression (which will reduce hyperactivity) and/or differential effects (i.e. some suppression and some enhancement which could break up hypersynchrony) for neural activity. We are currently working on optimizing these parameters for different areas of the IC in the guinea pig model. Our proposed therapy is innovative and hasn’t been published on for tinnitus treatment, so there is no literature for this optimization to my knowledge. Even more importantly, we have found that certain paradigms can actually leave lasting suppressive effects for over 1 hour after 2-3 minutes of stimulation. Since these details are not yet published, I can’t explain the paradigms used, which is why I didn’t include the them in the presentation. Our goal is to find the right paradigm that will cause the most suppression/differential effects while inducing long-term plasticity for each area of the IC. These findings would lead to a treatment that could potentially cure tinnitus with only 2-3 minutes of treatment each morning! The device we have in mind will be user friendly and easy to implement, making the treatment very feasible for patients, which would also give us the option to easily test for optimization in human trials with only a limited amount of evidence in the animal model.

Please contact me with any other questions!

Great questions!

The acoustic stimulation will be used to induce long term plasticity. In preliminary experiments, we have seen that somatosensory stimulation alone can suppress acoustic driven and spontaneous neural activity in the IC, but it does not leave any long term effects since neural responses return to normal immediately after the stimulation. However, if the somatosensory stimulation is paired with acoustic stimulation, we see suppression of activity that lasts for over one hour after 2-3 minutes of stimulation. This is important for implementing a device in humans, as it would only require a short therapy session to suppress tinnitus for extended periods of time. The acoustic stimulation itself is a combination of different tones and/or broadband noise depending on the location in the IC. Since we haven’t published on this data yet, I can’t tell you the exact parameters, but I can tell you that different paradigms yield different results at different locations. The acoustic stimulation is applied via a speaker in front of the guinea pig’s ear. In our experiments, the speaker is connected to a tube that transmits the sounds directly to the animal’s ear canal to prevent noise in our recordings, but for human implementation, we would just use normal headphones.

To determine dimensions, we used a histological process to create 3-D reconstructions. Details of this process can be found in a recent publication: “Three-dimensional brain reconstruction of in vivo electrode tracks for neuroscience and neural prosthetic applications”, Markovitz et. al., Frontiers in Neural Circuits. Here’s a quick summary. We dye our recording electrodes with a fluorescent dye before placing them in the brain. After the experiment, we preserve the brain for two weeks before slicing it into 60 micron-thick slices. We then image these slices with normal light and with fluorescent light, and we use a computer program to stack the images into a 3-D reconstruction of the brain. Here, we can see the actual boundaries of the IC, along with the locations of the electrode tracts accurate within 100 microns. For the presentation, I grouped electrode tracts into the squares of the grid that you see in the presentation to make it easier to see the differences in thresholds (it becomes difficult to see anything with so many individual electrode tracts on the picture, so grouping them is necessary). To determine the threshold for each square, I simply took the average of the thresholds across all electrodes in the square. Because of the reconstructions, the locations of these squares on the IC are fairly accurate.

Thanks for your questions!

Thanks Dr. Johnson!

That’s right! Studies have shown that visual stimuli can be used to treat phantom limb pain. It’s another example of multi-sensory integration for treating disorders of the brain. Hopefully, this work may inspire others to consider multimodal integration as an asset.

Of course! We recognize how difficult it can be for some people. Hopefully we can come up with a simple, safe and convenient way to treat this disorder.