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the sensory-salience dysregulation model

(Section link)
(SSDM)

narrative summary

The Sensory–Salience Dysregulation Model (Melanthiou et al., 2026) (SSDM) proposes a unified neurobiological framework for tinnitus and misophonia by emphasizing interacting sensory, salience, and autonomic processes rather than isolated auditory or emotional pathways. Both conditions are understood as arising from abnormal sensory encoding with excessive central gain, where amplified auditory signals emerge either from peripheral damage and compensatory central hyperactivity in tinnitus (producing phantom sounds) or from exaggerated neural responses to specific external triggers in misophonia due to abnormal connectivity between auditory cortex, anterior insula, and premotor regions. These amplified signals then drive overactivation of the salience network (ACC, insula, amygdala), which assigns excessive importance to the sounds and fails to habituate them, causing persistent tagging as salient or threatening and recruiting attentional systems. Finally, the model highlights autonomic dysregulation reinforced through predictive coding errors, where impaired sensory gating increases uncertainty in incoming input, shifting perception toward top-down predictions . Because the brain estimates reliability based on the consistency of sensory input and prior experience (precision Weighting), degraded or noisy input leads it to overweight internal predictions. This results in maladaptive internal models that manifest as phantom percepts in tinnitus and intrusive, emotionally charged responses in misophonia, with these patterns becoming reinforced over time through neuroplasticity.

predictions of the SSDM

the authors describes four main predictions made by the SSDM

• symptoms correlating with hyperconnectivity: there will be a strong positive correlation between symptom severity and abnormalities in precision weighting inside the salience network, as evident by hyperconnectivity both at rest and during sound exposure.
• efficacy of neuromodulator interventions: neuromodulator interventions for salience network excitability (e.g., low-frequency or inhibitory patterned TMS to the right anterior insula or dorsal ACC, or excitatory stimulation of dorsolateral prefrontal regions) should reduce distress to sounds regardless of the sounds perceptual qualities.
• Dissociation between perceptual and affective outcomes: modulation of autonomic regulation should reduce symptoms without changing the auditory percept, as the primary dysfunction is in early sensory gating and precision weighting.
• modulating symptom expression via manipulation of sensory precision and expectations: The model proposes that altering sensory precision and expectations, through combined sound-based therapies and cognitive restructuring, can rebalance bottom-up and top-down processing, thereby reducing the salience and autonomic reactivity to auditory stimuli in a way that is empirically testable.
  (Melanthiou et al., 2026)

detailed notes

• a model introduced in (Melanthiou et al., 2026) that seeks to give a unified explanation for the neurobiological framework of both tinnitus and Misophonia
• instead of isolating auditory / emotional pathways.
• sees both Misophonia and tinnitus as arising from three primary sources:

Abnormal sensory encoding with excessive central gain

• Common theme- excessive central gain results in amplified auditory signals
• In tinnitus- peripheral auditory damage (ex hair cell loss, synaptic injury) results in compensatory hyperactivity of central auditory system, creating the persistent phantom sounds
• In Misophonia- exaggerated neural responses the specific external cues resulting from abnormal brin connectivity with the auditory cortex, anterior insula, and premotor regions

Overactivation of the salience network

• common theme- amplified sensory inputs engage salience network (anterior cingulate cortex (ACC), insula, and amygdala), assigning the stimuli more importance. in both instances, salience network fails to downregulate/habituate sounds, and instead continuously highlights and assigns importance to them, which in turn engaging the attentional system due to the sounds being marked as threating.
• In Tinnitus- emotional salience is given to otherwise neutral phantom sound, and hypoconnectivities increases chances of the phantom sound capturing the attention system.
• In misophonia-

autonomic dysregulation reinforced through predictive coding errors

• core issues- failure in up stream sensory gating
• precision weighting- how much the brain weights prediction error (sensory input vs expectations) based on its estimated reliability which is inferred from the consistency of sensory input and prior experience.
• predictive coding – the brain’s process of generating predictions about sensory input and updating them based on the precision-weighted difference between predictions and actual input.
  • predictive coding error- the breakdown of predictive coding. applied to the SSDM proposing that tinnitus and misophonia emerge from an imbalance between bottom-up sensory information and top-down predictions; deafferentation or abnormal gating increases sensory uncertainty, causing the brain to rely on maladaptive internal models that manifest as phantom or intrusive percepts.