Highlights
- •Patients enrolled in an rTMS clinical trial for tinnitus underwent fMRI at baseline.
- •Patients underwent the MSIT attentional conflict fMRI task.
- •1 Hz rTMS intervention significantly reduced tinnitus symptoms (i.e. awareness).
- •Prefrontal and parietal recruitment during MSIT negatively predicted rTMS response.
- •These regions may be biomarkers for improving patient selection.
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,
1 Hz, and 10 Hz (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
1 Hz 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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: June 02, 2017
Accepted:
May 19,
2017
Received in revised form:
May 9,
2017
Received:
February 11,
2017
Identification
Copyright
© 2017 Elsevier Inc. All rights reserved.
