Peter Alexander Tass

Counteracting tinnitus by acoustic coordinated reset neuromodulation

PURPOSE Subjective tinnitus is associated with pathologic enhanced neuronal synchronization. We used a model based desynchronization technique, acoustic coordinated reset (CR) neuromodulation, to specifically counteract tinnitus-related neuronal synchrony thereby inducing an unlearning of pathological synaptic connectivity and neuronal synchrony. METHODS In a prospective, randomized, single blind, placebo-controlled trial in 63 patients with chronic tonal tinnitus and up to 50 dB hearing loss we studied safety and efficacy of different doses of acoustic CR neuromodulation. We measured visual analogue scale and tinnitus questionnaire (TQ) scores and spontaneous EEG. RESULTS CR treatment was safe, well-tolerated and caused a significant decrease of tinnitus loudness and symptoms. Placebo treatment did not lead to any significant changes. Effects gained in 12 weeks of treatment persisted through a preplanned 4-week therapy pause and showed sustained long-term effects after 10 months of therapy: response, i.e. a reduction of at least 6 TQ points, was obtained in 75% of patients with a mean TQ reduction of 50% among responders. CR therapy significantly lowered tinnitus frequency and reversed the tinnitus related EEG alterations. CONCLUSION The CR-induced reduction of tinnitus and underlying neuronal characteristics indicates a new non-invasive therapy which might also be applicable to other conditions with neuronal hypersynchrony.

Desynchronizing the abnormally synchronized neural activity in the subthalamic nucleus: a modeling study

A mathematical model of a target area for deep brain stimulation was used to investigate the effects of electrical stimulation on pathologically synchronized clusters of neurons. In total, three newly developed stimulation techniques based on multisite coordinated reset and delayed feedback were tested and compared with a high-frequency stimulation method that is currently used as a standard stimulation protocol for deep brain stimulation. By modeling both excitatory and inhibitory actions of the electrical stimulation, we revealed the desynchronization impacts of the novel stimulation techniques. This contrasts with standard high-frequency stimulation, which failed to desynchronize the target population and whose inhibitory effects blocked all neuronal activity. We also explored the demand-controlled character of the proposed methods, and demonstrated that the amount of stimulation current required was considerably smaller than that for high-frequency stimulation. These novel stimulation methods appear to be superior to standard high-frequency stimulation techniques, and we propose the methods now be used for deep brain stimulation.

Anti-kindling achieved by stimulation targeting slow synaptic dynamics

PURPOSE Different stimulation techniques are introduced which specifically modulate the slow synaptic dynamics in a neuronal network model of the subthalamic nucleus with activity dependent synaptic plasticity. METHODS A modeling approach is utilized to investigate the effects of the different stimulation techniques. In particular, the short-term and long-term outcome is studied in a mathematical model for a population of bursting STN neurons subject to synaptic plasticity with symmetric spike timing characteristics. In our mathematical model in the absence of stimulation synchronized network states with strong connectivity (modeling disease states) as well as desynchronized states with weak connectivity (modeling healthy states) are stable. RESULTS We demonstrate that different stimulation techniques induce an anti-kindling by shifting the target population to a weakly connected, desynchronized state. Intriguingly, long-term anti-kindling can even be achieved although during stimulus delivery the neuronal synchrony hardly decreases or even slightly increases. The therapeutic index and the impact of inhibition, calculated to compare the different stimulation techniques, indicate that coordinated rest stimulation might be particularly robust and reliable. CONCLUSIONS The presented stimulation strategies and the results of our modeling study might have strong implications in the context of deep brain stimulation.

Rebuttal to reply by G. Rücker and G. Antes on Tass et al. "Counteracting tinnitus by acoustic coordinated reset neuromodulation", Restorative neurology and neuroscience Vol. 30(2), 2012.

We would like to thank Dr. Gerta Rucker and Prof. Gerd Antes for their interest in our article “Counteracting tinnitus by acoustic coordinated reset neuromodulation” and for their suggestions especially as the Cochrane collaboration has a long-standing track record for reviewing tinnitus therapies. Specifically, they found very limited evidence for efficacy of commonly used tinnitus therapies (www.thecochranelibrary.com) such as tinnitus retraining therapy (TRT, Phillips & McFarran 2010) and cognitive behavioral therapy (CBT, MartinezDevesa et al. 2010). Cochrane defines evidence as not limited to randomized controlled trials and metaanalyses but including the best available evidence at any one time encompassing all kinds of medical research, which can be also the result from basic