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Pascal Senn

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YNICL Journal 2026 Journal Article

Altered parietal multisensory integration in chronic tinnitus during closed-loop real-time fMRI auditory downregulation

  • Nicolas Gninenko
  • Pascal Senn
  • Sven Haller
  • Dimitri Van De Ville

Chronic subjective tinnitus is the most common form of tinnitus and refers to an internal persistent phantom auditory perception. Evidence from neuroimaging studies has established tinnitus and its associated distress as a brain network disorder, with multiple brain regions displaying dysregulated activity or connectivity extending way beyond the auditory pathway. Hyperactivity in the auditory cortex has been associated with perceived tinnitus loudness, and somatosensory-auditory interactions have recently been involved in promising treatment avenues through their disruption using non-invasive or bimodal neuromodulation techniques, albeit with low mechanistic evidence. In this study, we evaluated the neural effects of prolonged downregulation of bilateral auditory cortex activity mediated by real-time fMRI neurofeedback in individuals with moderate to severe (Tinnitus Handicap Inventory [THI] scores ≥ 48) chronic tinnitus. Twenty-one participants (aged 49 ± 11.4 years old, 16 males, 5 females) completed 15 fMRI neurofeedback sessions over 3-4 months each, as part of a randomized clinical trial (ClinicalTrials.gov: NCT05737888) comparing neurofeedback interventions over the current standard of care, cognitive behavioral therapy (CBT). We performed whole-brain general linear modeling analyses to delineate regulated brain areas, accounting for age, gender, and THI scores at baseline. Task-modulated functional connectivity analyses were carried out using psychophysiological interactions to unveil associated connectivity patterns emerging during cognitively demanding tinnitus defocalization. Most participants succeeded at reducing the average activity of their auditory cortex throughout the training. Whole brain analyses additionally revealed a strong downregulation of parietal operculum 3 (OP3), a region previously reported to be activated in the right hemisphere during experimentally induced transient phantom percepts. In accordance with the hypothesis that OP3 may mediate the integration of multisensory inputs in tinnitus, we have shown that both left and right auditory cortices decrease their connectivity with OP3 during closed-loop auditory downregulation. Moreover, we observed a reduced connectivity of bilateral OP3 with a functional multisensory integration network that was previously found to be engaged by the primary and secondary auditory cortices during audio-tactile integration. These findings support the hypothesis of OP3 having a key role in multisensory integration stemming from altered somatosensory-auditory crosstalk in chronic tinnitus. Targeted neuromodulation to desynchronize the connectivity between OP3 and the auditory cortex could further inform our understanding of the mechanisms behind recent successful bimodal interventions for reducing tinnitus.

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YNICL Journal 2017 Journal Article

Continuous vs. intermittent neurofeedback to regulate auditory cortex activity of tinnitus patients using real-time fMRI - A pilot study

  • Kirsten Emmert
  • Rotem Kopel
  • Yury Koush
  • Raphael Maire
  • Pascal Senn
  • Dimitri Van De Ville
  • Sven Haller

The emerging technique of real-time fMRI neurofeedback trains individuals to regulate their own brain activity via feedback from an fMRI measure of neural activity. Optimum feedback presentation has yet to be determined, particularly when working with clinical populations. To this end, we compared continuous against intermittent feedback in subjects with tinnitus. Fourteen participants with tinnitus completed the whole experiment consisting of nine runs (3 runs × 3 days). Prior to the neurofeedback, the target region was localized within the auditory cortex using auditory stimulation (1 kHz tone pulsating at 6 Hz) in an ON-OFF block design. During neurofeedback runs, participants received either continuous (n = 7, age 46.84 ± 12.01, Tinnitus Functional Index (TFI) 49.43 ± 15.70) or intermittent feedback (only after the regulation block) (n = 7, age 47.42 ± 12.39, TFI 49.82 ± 20.28). Participants were asked to decrease auditory cortex activity that was presented to them by a moving bar. In the first and the last session, participants also underwent arterial spin labeling (ASL) and resting-state fMRI imaging. We assessed tinnitus severity using the TFI questionnaire before all sessions, directly after all sessions and six weeks after all sessions. We then compared neuroimaging results from neurofeedback using a general linear model (GLM) and region-of-interest analysis as well as behavior measures employing a repeated-measures ANOVA. In addition, we looked at the seed-based connectivity of the auditory cortex using resting-state data and the cerebral blood flow using ASL data. GLM group analysis revealed that a considerable part of the target region within the auditory cortex was significantly deactivated during neurofeedback. When comparing continuous and intermittent feedback groups, the continuous group showed a stronger deactivation of parts of the target region, specifically the secondary auditory cortex. This result was confirmed in the region-of-interest analysis that showed a significant down-regulation effect for the continuous but not the intermittent group. Additionally, continuous feedback led to a slightly stronger effect over time while intermittent feedback showed best results in the first session. Behaviorally, there was no significant effect on the total TFI score, though on a descriptive level TFI scores tended to decrease after all sessions and in the six weeks follow up in the continuous group. Seed-based connectivity with a fixed-effects analysis revealed that functional connectivity increased over sessions in the posterior cingulate cortex, premotor area and part of the insula when looking at all patients while cerebral blood flow did not change significantly over time. Overall, these results show that continuous feedback is suitable for long-term neurofeedback experiments while intermittent feedback presentation promises good results for single session experiments when using the auditory cortex as a target region. In particular, the down-regulation effect is more pronounced in the secondary auditory cortex, which might be more susceptible to voluntary modulation in comparison to a primary sensory region.

Details DOI
v2026.09.13