Detection of hyperacusis condition in tinnitus patients based on PLSC features that link audiogram and fMRI tonotopy responses

Tinnitus is the chronic perception of ringing or other phantom sounds. Some tinnitus patients addi- tionally suffer from loudness hyperacusis that is the over-sensitivity to environmental sounds. Here, we recruited eight patients with unilateral hearing loss and tinnitus, among which four also have loudness hyperacusis. For every patient, the audiogram was acquired by measuring the audible thresholds for 9 frequency presentations in the range 125Hz-8kHz with steps of half an octave. The fMRI data was recorded on a 7T MRI scanner that allows exquisite spatial resolution of 1mm3. The experimental paradigm was according to the tonotopic mapping experiment by (Da Costa et al., 2011), which consists in presenting a sequence of 15 pure frequency tones in 14 cycles (88Hz- 11340Hz). Voxels from the auditory cortex are then extracted and their timecourse is fitted to the sine/cosine with the period of the block-based paradigm, which gives access to the amplitude and the phase of the response. Voxels are labeled using the relationship between the phase and the presented frequency, and then amplitudes of voxels with same label are averaged resulting into 15 fMRI features/subject. We then use partial least-squares correlation (PLSC; Krishnan et al., 2011) to establish the link between the audiogram measures and the fMRI tonotopy responses. By max- imizing correlation in a multivariate way, PLSC identifies a set of latent variables (LVs) that each contain an fMRI saliency vector and two audiogram saliency vectors (one for each group; i.e., hy- peracusis and non-hyperacusis). Using permutation testing, we found evidence for a single LV being significant (p

Neuroimaging of human auditory cortex

Naghmeh Ghazaleh

Modern neuroimaging technologies provide us with non-invasive methods for study- ing structure and function, and plasticity of the human auditory cortex. Here we have acquired high spatial resolution functional magnetic resonance imaging (fMRI) data of the auditory cortex in patients with unilateral hearing loss and tinnitus. Compared to healthy controls, we found evidence of over-representation and hyperactivity in parts of cortical tonotopic map that correspond to low frequencies sounds, irrespective of the hearing loss and tinnitus range, which in most cases affected higher frequencies. These findings suggest that hearing loss has a destabilizing effect on the tonotopic organization in primary auditory cortex that is not restricted to the corresponding frequency range of hearing loss and tinnitus. One of the challenges in tinnitus studies is the high relevance of the hyperacusis con- dition in these patients. The similarity and co-occurrence of these two disorders con- tributes to the debate about the specificity of findings associated with tinnitus alone. For classifying tinnitus patients with and without hyperacusis, we thus implemented partial least square correlation (PLSC) analysis that builds upon the cross-covariance information between audiogram and fMRI data. This method provides us with a multi modal measure to successfully detect the hyperacusis condition in tinnitus patients with 80% cross-validation accuracy, for the first time. The PLSC driven biomarker, also yields the brain area playing a major role in the condition. There is a vast heterogeneity in the anatomy of auditory cortex across subjects, therefore individualized delineation the exact border between primary and secondary auditory cortex is a demanding research topic. Here we established a model of ex- trinsic connectivity of auditory cortex with the two other regions of the brain that have discriminative connectivity with primary and secondary auditory cortices. The resting state fMRI connectivity features are used for segmentation and are performed exploiting two methods as dynamical causal modeling (DCM) of effective connectivity with 74% accuracy and functional connectivity with 71% accuracy. This data-driven segmentation method, not only facilitate the definition of auditory cortex subregions for fundamental research in the normal brain, but also yields a useful tool for following the modification in the functional anatomy of this region as a result of hearing disorders like tinnitus.

EPFL2017

High-Resolution fMRI of Auditory Cortical Map Changes in Unilateral Hearing Loss and Tinnitus

Naghmeh Ghazaleh, Melissa Saenz, Dimitri Nestor Alice Van De Ville, Wietske Van der Zwaag

Animal models of hearing loss and tinnitus observe pathological neural activity in the tonotopic frequency maps of the primary auditory cortex. Here, we applied ultra high-field fMRI at 7 T to test whether human patients with unilateral hearing loss and tinnitus also show altered functional activity in the primary auditory cortex. The high spatial resolution afforded by 7 T imaging allowed tonotopic mapping of primary auditory cortex on an individual subject basis. Eleven patients with unilateral hearing loss and tinnitus were compared to normal-hearing controls. Patients showed an over-representation and hyperactivity in a region of the cortical map corresponding to low frequencies sounds, irrespective of the hearing loss and tinnitus range, which in most cases affected higher frequencies. This finding of hyperactivity in low frequency map regions, irrespective of hearing loss range, is consistent with some previous studies in animal models and corroborates a previous study of human tinnitus. Thus these findings contribute to accumulating evidence that gross cortical tonotopic map reorganization is not a causal factor of tinnitus.

Springer Verlag2017

Lateralization of the primary auditory cortex, in patients with unilateral tinnitus

Naghmeh Ghazaleh, Melissa Saenz, Wietske Van der Zwaag

Tinnitus, the chronic perception of ringing or other phantom sounds, is typically associated with hearing loss. The reduction of auditory input that conveys to auditory cortex leads to the changes in the balance of excitatory and inhibitory activation of the corresponding neurons in this area and is possibly the cause of tinnitus. From the other hand a recent study (Gordon et al. Beain 2013) has shown that bilateral input protects the cortex from unilaterally driven reorganization. Based on this finding we could expect that in patient with unilateral hearing loss and tinnitus the input from unimpaired ear has not been transfered sufficiently to the bilateral hemisphere and this loss of input has resulted in reorganization in neuronal activity of the auditory cortex. To test this hypothesis we compare the amplitude of the neuronal activity bold response of the auditory cortex in the ipsilateral and contralateral hemisphere to the hearing ear in response to different frequency tones. Ten tinnitus patients with chronic unilateral hearing loss and tinnitus and age-matched normal controls (ages 26-49) were tested. (Patients had chronic subjective non-pulsatile tinnitus associated with moderate to severe unilateral sensorineural hearing loss in one ear only with at least PTA>40dB on three consecutive frequencies between 1 and 4 KHz; tinnitus duration < 6 months). The recruitment of patients with unilateral hearing loss allowed unimpaired sound delivery via the unimpaired ear, bypassing any abnormal responsiveness at the peripheral level. Our high-resolution functional MRI at 7 Tesla (1.5 mm isotropic voxels) (Da Costa et al. J Neurosci 2011) provides us fine scale tonotopic maps in controls and tinnitus patients and using that we are able to compare the amplitude of the neural activity in the auditory cortex of the unilateral and ipsilateral hemisphere to the hearing ear for each group of different frequency responding neurons. Our first finding shows that the activity difference in tinnitus patient is higher than the activity difference in controls. In more detail the activity amplitude in the contralateral hemisphere to the hearing ear in tinnitus patient is much higher than the activity amplitude in ipsilateral hemisphere, in comparison to controls. This result suggests that the auditory pathway in tinnitus patients is less capable to convey the sound bilaterally and it could be a probable cause of their tinnitus.