1. Neural Correlates of White Matter Integrity in Tinnitus: Tract-Based Spatial Statistics Fahad Alhazmi PhD student

2. Talk outline Background Aim Study questions Study design Image acquisition Data analysis Audiogram results Neuroimaging findings Summary

3. Background Diffusion tensor imaging (DTI) can measure the displacement of water molecules inside white matter tracts, which provides information of white matter integrity (Ling et al., 2012). The most common DTI parameter used is fractional anisotropy (FA) that measures the fractional of diffusion tensor, and reflects white matter integrity and brain network reorganization. Brain structural atrophy and functional dysfunction have been reported in tinnitus population at different auditory and non-auditory brain regions.

4. Aim The aim of this study is to investigate the influence of tinnitus perception on white matter microstructure integrity using unbiased whole brain voxel-wise analysis.

5. Study questions Is the integrity of white matter microstructure altered in chronic tinnitus patients? Does tinnitus severity has any effect on white matter microstructure integrity? Does tinnitus laterality play a role on the alterations of microstructure white matter integrity? Do anxiety and depression have an effect on the white matter microstructure integrity of tinnitus patients?

6. Study design Behavior assessments Edinburgh Handedness Inventory Clinical audiograms Hospital anxiety and depression scale Tinnitus assessments (THI & TFI) Recruitment Normal health controls (NHC) Chronic tinnitus patients (TIN) Neuroimaging assessments Structural session (sMRI) Clinical session (T2 MRI) Diffusion session (dMRI)

7. Subjects’ characteristics NHCTIN N2026 Age (Yrs)47±1045±12 Gender (M/F)9/1118/8 Handedness (R/L)19/121/5 HADS11.6 ± 3.810.2 ± 6.7 Hearing loss average (dB)14.5±714.7±5.5 THIN/A26±19 TFIN/A36±21 Tinnitus onset (Yrs)N/A9±89±8 Tinnitus lateralization (Unilateral/ Bilateral)N/A10/16 Tinnitus severity (Coping/Suffering)N/A13/13

8. Image acquisition Using a Siemens 3T Trio (Siemens, Erlangen, Germany) with a standard 8 channels head coil performed in this study. MRI scanner sMRIdMRI Structural images were acquired to perform spatial normalization and localization using 3D MDEFT sequence. The diffusion images were acquired with 60 directions and b-values 0-1200 s/mm 3

9. Data analysis Diffusion MRI data were processed using FDT and TBSS toolboxes as parts of FMRIB Software Library (FSL), Oxford, UK (Smith, Jenkinson et al. 2006). ◦ Non-brain tissues were extraction from structural and diffusion images using BET toolbox. ◦ DTI-volume with a b-value 1200 s/mm 2 was affine registered to the b0 volume after eddy current distortion and head motion correction. ◦ Every FA image was co-registered to the FA target image in a stander space (MNI 152). ◦ All alignment FA images were averaged, and then white matter skeleton was generated. ◦ Each subject’s FA data was projected into the mean white matter tract skeleton. ◦ Group comparisons were carried out between groups. (Acosta-Cabronero and Nestor 2014)

10. Audiogram results Frequencies (kHz) Hearing loss thresholds (dB)

11. Neuroimaging findings Mean FA t=2.11, P=0.042

12. Neuroimaging findings L R R L

13. Tinnitus severity ◦ No significant differences of microstructure white matter integrity between tinnitus copers and suffers subgroups.

14. Neuroimaging findings Tinnitus laterality R L R L

15. Neuroimaging findings Anxiety and depression in tinnitus L L RR

16. Summary Is the integrity of white matter microstructure altered in chronic tinnitus patients? ◦ We found a significant reduction of FA in tinnitus patients comparing to normal healthy controls. Does tinnitus severity has any effect on white matter microstructure integrity? ◦ Tinnitus severity does not seem to have an effect of WM microstructure integrity. Does tinnitus laterality play a role on the alterations of microstructure white matter integrity? ◦ Corpus callosum shows the involvement in tinnitus laterality. Do anxiety and depression have an effect on the alterations of white matter microstructure integrity? ◦ A significant reduction of FA values found in Cingulum WM tracts in tinnitus patients with high score of HADS comparing to tinnitus patients with low HADS scores.

17. References Acosta-Cabronero, J. and P. J. Nestor (2014). "Diffusion tensor imaging in Alzheimer's disease: insights into the limbic- diencephalic network and methodological considerations." Front Aging Neurosci 6: 266. Ling, J. M., A. Peña, R. A. Yeo, F. L. Merideth, S. Klimaj, C. Gasparovic and A. R. Mayer (2012). "Biomarkers of increased diffusion anisotropy in semi-acute mild traumatic brain injury: a longitudinal perspective." Brain 135(4): 1281-1292. Smith, S. M., M. Jenkinson, H. Johansen-Berg, D. Rueckert, T. E. Nichols, C. E. Mackay, K. E. Watkins, O. Ciccarelli, M. Z. Cader, P. M. Matthews and T. E. Behrens (2006). "Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data." Neuroimage 31(4): 1487-1505.

18. Acknowledgement My supervisor team ◦ Dr Vanessa Sluming ◦ Prof Graham Kemp Collaborators – Dr Ian Mackenzie – Mr Tony Kay – Dr Jamaan Alghamdi MARIARC – Mr Bill Bimson – Miss Val Adam Research project Sponsor – Cultural Bureau of Saudi Arabia in the UK Thank you for attention Thank you for attention