Heading for Personalized rTMS in Tinnitus: Reliability of Individualized Stimulation Protocols in Behavioral and Electrophysiological Responses

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Abstract
Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool potentially modulating pathological brain activity. Its clinical effectiveness is hampered by varying results and characterized by inter-individual variability in treatment responses. RTMS individualization might constitute a useful strategy to overcome this variability. A precondition for this approach would be that repeatedly applied protocols result in reliable effects. The condition tinnitus provides the advantage of immediate behavioral consequences (tinnitus loudness changes) after interventions and thus offers an excellent model to exemplify TMS personalization. Objective: The aim was to investigate the test–retest reliability of short rTMS stimulations in modifying tinnitus loudness and oscillatory brain activity as well as to examine the feasibility of rTMS individualization in tinnitus. Methods: Three short verum (1, 10, 20 Hz; 200 pulses) and one sham (0.1 Hz; 20 pulses) rTMS protocol were administered on two different days in 22 tinnitus patients. Before and after each protocol, oscillatory brain activity was recorded with electroencephalography (EEG), together with behavioral tinnitus loudness ratings. RTMS individualization was executed on the basis of behavioral and electrophysiological responses. Stimulation responders were identified via consistent sham-superior increases in tinnitus loudness (behavioral responders) and alpha power increases or gamma power decreases (alpha responders/gamma responders) in accordance with the prevalent neurophysiological models for tinnitus. Results: It was feasible to identify individualized rTMS protocols featuring reliable tinnitus loudness changes (55% behavioral responder), alpha increases (91% alpha responder) and gamma decreases (100% gamma responder), respectively. Alpha responses primary occurred over parieto-occipital areas, whereas gamma responses mainly appeared over frontal regions. On the contrary, test–retest correlation analyses per protocol at a group level were not significant neither for behavioral nor for electrophysiological effects. No associations between behavioral and EEG responses were found. Conclusion: RTMS individualization via behavioral and electrophysiological data in tinnitus can be considered as a feasible approach to overcome low reliability at the group level. The present results open the discussion favoring personalization utilizing neurophysiological markers rather than behavioral responses. These insights are not only useful for the rTMS treatment of tinnitus but also for neuromodulation interventions in other pathologies, as our results suggest that the individualization of stimulation protocols is feasible despite absent group-level reliability.
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Funding Information
  • European Union's Horizon 2020 Marie Sklodowska-Curie Actions (722046)
  • European Union's Horizon 2020 Framework Programme (848261)

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