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The Neuroscience of Tinnitus

Emerging neuroscientific research describes tinnitus as dysregulation across three primary brain networks: the salience network (SN), the default mode network (DMN), and the central executive network (CEN) (De Ridder et al., 2014, 2022). First described by Menon (2011) as the triple network model (TNM), functional connectivity (FC) across these brain regions plays a distinct role in certain psychopathology: the SN is responsible for enhancing the salience of sensory input (Uddin, 2016); the DMN governs self-referential thought, which influences cognitive and emotional processing (Buckner et al., 2008); and the CEN regulates priority cognitive functions that influence attention and executive decisions (Seeley et al., 2007).

 

Recent neuroimaging studies consistently show abnormal FC within TNM regions among tinnitus sufferers. For example, Chen et al. (2018) investigated how tinnitus perception and distress correlates with altered FC within the TNM using functional magnetic resonance imaging (fMRI) and seed-based correlation analysis. Fifty chronic tinnitus participants were compared with fifty controls, matched for age and gender, and hyperactivity was observed between the SN and DMN in tinnitus participants which positively correlated with tinnitus handicap inventory (THI) scores, a validated measure of tinnitus impact (Newman et al., 1998). In contrast, hypoactivity was observed between the DMN-CEN in tinnitus participants which correlated with heightened emotional response and attentional focus on tinnitus.  Zhou et al. (2022) also demonstrated that tinnitus is linked to disruptions in FC within the TNM. In a fMRI and seed-based functional connectivity analysis, forty-five chronic tinnitus participants and forty-five healthy controls were matched for demographic variables such as age and gender. Distress levels were measured using the tinnitus handicap inventory (THI) and tinnitus functional index (TFI) to assess tinnitus impact on emotional and functional domains. Elevated SN-DMN connectivity and reduced DMN-CEN connectivity were observed in tinnitus participants, which positively correlated with levels of tinnitus distress and perception. De Ridder et al. (2022) posits that increased SN-DMN connectivity aligns with a neurological predisposition to engage in self-referential and distressful thoughts about tinnitus, whereas reduced DMN-CEN connectivity is associated with weakened cognitive regulation, contributing to difficulty in shifting attention away from the tinnitus. In a study using resting-state electroencephalography (rs-EEG), Xiong et al. (2023), specifically found enhanced connectivity between the SN’s anterior insula (AI) and auditory cortex, as well as between the DMN’s parahippocampal cortex (PHC) and posterior cingulate cortex (PCC). These patterns were more pronounced in moderate-to-severe tinnitus cases and were associated with higher levels of distress and attentional focus on tinnitus, as reflected by elevated THI and TFI scores. A consistent finding in tinnitus participants therefore appears to be SN-DMN and SN-CEN hyperactivity and DMN-CEN hypoactivity as depicted in Figure 1.

 

Figure 1. Triple network model (TNM) of tinnitus showing dysregulation parameters.

Non-invasive neuromodulation techniques that target these dysfunctional pathways are therefore of particular interest. Laundry et al. (2020) and Trevis et al. (2018) demonstrated that cognitive therapy (CT), including CBT, helps individuals reframe negative perceptions and reduce emotional distress associated with tinnitus. However, we must turn to related applications of CT to gain insights on its effect on TNM pathways. Yoshino et al. (2018) used resting-state fMRI (rs-fMRI) to show that chronic pain subjects who underwent cognitive therapy (CT) exhibited improved DMN-CEN regulation, which is particularly relevant given the parallels between the emotional responses to chronic pain and chronic tinnitus (De Ridder et al., 2022; Johansson et al., 2024). Comparable findings have been observed in disorders such as obsessive-compulsive disorder (OCD) (Fan et al., 2017) and major depressive disorder (MDD) (Pinto et al., 2014), which, like tinnitus, are characterised by disruptions in emotional and attentional brain networks (Cyr et al., 2020; Teng et al., 2022, 2024). Zimmerman et al. (2019) found that mindfulness based cognitive therapy (MBCT) increased DMN-CEN connectivity and regulation which positively correlated with a reduction in distress in tinnitus subjects. Bauer et al. (2017) used fMRI to demonstrate that CT increased DMN-CEN connectivity which correlated with reduced emotional reactivity and reduced tinnitus distress. Cognitive therapies therefore appear to have a specific role in modulating the DMN-CEN pathway which may explain why, as a monomodal therapy it is helpful in reducing tinnitus distress but not so for tinnitus perception which is more strongly associated with the SN pathways. However, the inclusion of CT in a multimodal approach clearly holds promise.

Neurofeedback, a technique that trains individuals to regulate brainwave activity via real-time monitoring of EEG signals, has been successfully used to treat post-traumatic stress disorder (PTSD) (Vlachou et al., 2022) and attention deficit hyperactivity disorder (ADHD) (Reiter et al., 2016), two conditions which display hyperactivity in SN-DMN functional connections; a phenomenon also found in tinnitus sufferers (Abdallah et al., 2019; Sidlauskaite et al., 2016). When considered within the context of the triple network model, neurofeedback has been found to be a promising tool for modulating key brain networks implicated in tinnitus (Barrenechea, 2022). For example, Guntensperger et al. (2017, 2019), demonstrated that neurofeedback can modulate key regions of the DMN, such as the posterior cingulate cortex (PCC) which correlated with reduction in tinnitus-related distress. Similarly, Kleinjung et al. (2023) and Jensen et al. (2023) demonstrated that neurofeedback can downregulate hyperactivity of the SN-DMN and SN-CEN by neuromodulating the anterior insular (AI) and anterior cingulate cortex (ACC) regions involved in the perceptual salience and attentional focus on tinnitus. One challenge with neurofeedback research, however, is the variability across studies on the optimal training protocol (Rogala et al., 2016). Notwithstanding, a protocol developed by Crocetti et al. (2011) aimed at reducing delta and beta waves and increasing alpha activity, resulted in significant reductions in tinnitus perception, as evidenced by improved THI scores. This alpha/delta/beta training protocol has been refined by Jensen et al. (2020, 2023) and incorporated into the study design of this proposal. While speculative, neurofeedback potentially contributes to downregulating SN-DMN hyperactivity and therefore stands as a complementary component of a multimodal treatment approach to tinnitus.

Hypnosis, a therapeutic technique that induces a state of focused attention and heightened suggestibility, has been shown to modulate brain networks associated with tinnitus perception and distress (Laundry et al., 2017). In neuroimaging studies, hypnosis demonstrated enhanced cognitive control by modulating the dorsolateral prefrontal cortex (dlPFC) and posterior cingulate cortex (PCC) of the DMN-CEN pathway, which is implicated in rumination, a feature also in tinnitus (Oakley & Halligan, 2013; Hammond, 2019). In a neuroimaging study by Deeley et al. (2012), reduced DMN activity, measured by fMRI, correlated with the depth of the hypnotic state compared to the alert state. Similar findings were reported by McGeown et al. (2009), who used fMRI to demonstrate that hypnotic induction significantly decreased brain activity in the prefrontal cortex (PFC) of the DMN compared with the no-hypnosis state. An fMRI study by Jiang et al. (2017) observed down-regulation of the DMN-CEN pathway in tinnitus sufferers which was countered by a hypnotic state and which also decreased hyperactivity between the SN and CEN, leading to greater emotional regulation of sensory input from the SN and a reduced state of arousal. A review by Bralic (2023) of neuroimaging evidence for clinical hypnosis and its relation to the triple network model (TNM) of psychopathology, concluded that hypnosis downregulates attentional and emotional neural pathways by modulating hypoactivity at both a DMN-CEN, and SN-CEN level, which demonstrates a complementary contribution within a multimodal treatment approach.

In consideration of the triple network model (TNM) of tinnitus, it is evident from neuroimaging research, that cognitive therapy, neurofeedback, and hypnosis have a synergistic and complementary therapeutic neuromodulating effect on different functional connections of the TMN as depicted in Figure 2.

 

 

Figure 2. Trimodal tinnitus treatment model showing areas of main influence from cognitive therapy, neurofeedback, and hypnosis.

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