Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in auditory-limbic-arousal-cerebellar network

  1. Yu-Chen Chen
  2. Xiaowei Li
  3. Lijie Liu
  4. Jian Wang
  5. Chun-Qiang Lu
  6. Ming Yang
  7. Yun Jiao
  8. Feng-Chao Zang
  9. Kelly Radziwon
  10. Guang-Di Chen
  11. Wei Sun
  12. Vijaya Prakash Krishnan Muthaiah
  13. Richard Salvi  Is a corresponding author
  14. Gao-Jun Teng  Is a corresponding author
  1. Southeast University, China
  2. Dalhousie University, Canada
  3. University at Buffalo, The State University of New York, United States
5 figures and 2 tables

Figures

SS-induced tinnitus, hyperacusis, and startle reflex hyperactivity.

(A and B) 2AFC-tinnitus task for two representative rats during baseline days B1–B4, during Saline (SAL) treatment, during baseline days B6–B9, 2 hr post-sodium salicylate (SS), and days P1–P4 …

https://doi.org/10.7554/eLife.06576.003
SS depresses cochlear potentials but enhances central auditory evoked responses.

Effects of 300 mg/kg SS on peripheral and central electrophysiological measures. (A) Mean (+SEM, n = 5) compound action potential (CAP) input/output function (average of 6, 8, 12, 16, 20, 24, 30, …

https://doi.org/10.7554/eLife.06576.004
SS enhances and depresses amplitude of low-frequency fluctuations (ALFF) in specific CNS regions.

Panels A (most caudal) through K (most rostral) show MR images of rat brain. Significant differences in ALFF between the SS group vs Saline group 2 hr post-treatment. Thresholds set at a corrected p …

https://doi.org/10.7554/eLife.06576.005
Figure 4 with 1 supplement
SS alters functional connectivity (FC) in specific brain resions.

ROI FC heat maps showing the regions of the brain where SS induced a statistically significant increase in FC with the ROI placed in the ACx (top row), MGB (middle row), or inferior colliculus (IC) …

https://doi.org/10.7554/eLife.06576.007
Figure 4—figure supplement 1
The ALFF and FC data (seeds: ACx, MGB, and IC) for baseline and after SS application separately.
https://doi.org/10.7554/eLife.06576.008
Tinnitus–hyperacusis network model.

Schematic showing some of the major centers in the auditory pathway and areas in the CNS showing increased FC with the auditory cortex (ACx). Black lines show the neural transmission path from the …

https://doi.org/10.7554/eLife.06576.010

Tables

Table 1

SS-induced changes in amplitude of low-frequency fluctuations (ALFF); SS group vs Saline group; p < 0.001 corrected for multiple comparisons

https://doi.org/10.7554/eLife.06576.006
Brain regionLeftRight
Cluster sizet-valueCluster sizet-value
ALFF increased
 ACx1673.8121783.746
 IC723.383683.473
 MGB523.432483.339
 SSCx373.383403.402
 VCx323.342393.312
 SC404.123434.094
 AMY614.192603.923
 RN/PnO353.249283.290
 PnO/PMr123.498103.313
 PFL383.349373.292
 CB4383.349373.292
ALFF decreased
 HIP108−4.08792−4.002
 CPu72−3.77271−3.741
  1. Abbreviations: auditory cortex (ACx), inferior colliculus (IC), medial geniculate body (MGB), somatosensory cortex (SSCx), visual cortex (VCx), superior colliculi (SC), amygdala (AMY), gigantocellular reticular nucleus (RN), pontine reticular nucleus oral (PnO), paramedian raphe nucleus (PMr), parafloccular lobe of cerebellum (PFL), cerebellum lobule 4 (CB4), hippocampus (HIP), caudate-putamen (CPu), sodium salicylate (SS).

Table 2

SS-induced increases in functional connectivity (FC); p < 0.001 corrected for multiple comparisons

https://doi.org/10.7554/eLife.06576.009
Seed regionBrain regionLeftRight
Cluster sizet-valueCluster sizet-value
ACxMGB623.900703.859
IC823.912883.632
AMY673.897683.839
RN523.983483.902
PFL393.992353.954
CB4514.066534.070
MGBACx1954.0742104.084
HIP1624.0321784.109
ICMGB724.098604.013
HIP1404.0641313.904
  1. Abbreviations: medial geniculate body (MGB), inferior colliculus (IC), amygdala (AMY), reticular nucleus (RN), parafloccular lobe of cerebellum (PFL), cerebellum lobule 4 (CB4), auditory cortex (ACx), hippocampus (HIP), sodium salicylate (SS).

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