Neural activity during attentional conflict predicts reduction in tinnitus perception following rTMS

Abstract

Background Subjective idiopathic tinnitus is an intrusive, distracting, and potentially disabling disorder characterized by phantom perception of sounds. Although tinnitus has no approved pharmacologic treatment, recent evidence supports the use of repetitive transcranial magnetic stimulation (rTMS) to alleviate tinnitus symptoms. Objective/Hypothesis Repetitive TMS delivered over the middle superior temporal gyrus (STG) may alter ratings of tinnitus awareness and annoyance more than loudness due to change in attentional processing. STG has reciprocal connections to regions of the prefrontal cortex that mediate attention. To probe the hypothesized influence of STG stimulation on attention, a subset of patients with tinnitus enrolled in an rTMS clinical trial [n=12, 9 male, mean (sd) age = 49 (15) years] underwent an attentional conflict task before and after rTMS treatment in a repeated-measures functional magnetic resonance imaging (fMRI) study. Methods The Multi-Source Interference Task (MSIT), a Stroop-based visual attentional conflict fMRI task, was used to map participants’ neural processing of attentional conflict prior to rTMS intervention (Baseline) and after three rTMS intervention arms: Sham, 1Hz, and 10Hz (four sessions per arm, 1800 pulses per session, delivered @110% of the motor threshold over the posterior superior temporal gyrus). Results All measures of tinnitus severity (awareness, loudness, and annoyance) improved with 1Hz rTMS intervention; however, the greatest and most robust changes were observed for ratings of tinnitus awareness (mean 16% reduction in severity from Baseline, p<0.01). The MSIT elicited a similar pattern of neural activation among tinnitus participants at Baseline compared to an independent sample of 43 healthy comparison adults (r=0.801, p≤0.001). Linear regression with bootstrap resampling showed that greater recruitment of bilateral prefrontal and bilateral parietal regions by MSIT at Baseline corresponded with poorer treatment response. Individual regions’ activities explained 37–67% variance in participant treatment response, with left dorsolateral prefrontal cortex’s MSIT activity at Baseline explaining the greatest reduction in tinnitus awareness following 1 Hz stimulation. Although left dorsolateral prefrontal cortex activity at Baseline also predicted reduction in tinnitus loudness and annoyance (~50% variance explained), these symptoms were more strongly predicted by right middle occipital cortex (~70% variance explained) – suggesting that the neural predictors of symptom-specific treatment outcomes may be dissociable. Conclusion These candidate neural reactivity markers of treatment response have potential clinical value in identifying tinnitus sufferers who would or would not therapeutically benefit from rTMS intervention.

Repetitive Transcranial Magnetic Stimulation on Chronic Tinnitus: A Systematic Review and Meta-Analysis

“…sham rTMS Anders M 2010 [26] Czech Republic [27] The Netherlands [30] The USA [31] The USA James G 2018 [32] The USA [34] The USA Godbehere J 2019 [36] The…”

Phantom Perception of Sound and the Abnormal Cortical Inhibition System: An Electroencephalography (EEG) Study

“…These results are consistent with recent reports of an association between tinnitus and 2 major networks: a frontoparietal network, regulating cognitive control of attention, and a cinguloinsular saliency network, mediating pain and emotion. 63 The mechanisms underlying paired-pulse suppression are attributable to both presynaptic and postsynaptic GABAergic inhibition. The adaptation in the paired-pulse response depends on the interstimulus interval (ISI) between the adapter (PP-S1 in the current study) and adapted (probe, PP-S2 in the current study).…”

“…These results are consistent with recent reports of an association between tinnitus and 2 major networks: a frontoparietal network, regulating cognitive control of attention, and a cingulo-insular saliency network, mediating pain and emotion. 63…”

Transcranial Magnetic Stimulation in the Treatment of Tinnitus

“…Frontothalamic gating system may be formed by limbic and paralimbic structures for tinnitus [110]. James et al's study demonstrated with functional MRI that left superior dorsolateral prefrontal cortex had a greater role in predicting tinnitus awareness [111]. Combined prefrontal and temporal cortex rTMS was found to be more effective than temporal cortex rTMS alone [101,[112][113][114].…”

“…Khedr et al suggested that 10 or 20 Hz stimulation could also be effective [123]. James et al's study demonstrated that 1 Hz rTMS seemed to significantly decrease the awareness, loudness, and annoyance of tinnitus, but 10 Hz stimulus seemed to decrease only the awareness of tinnitus [111].…”