Study of tonotopic brain changes with functional MRI and FDG-PET in a patient with unilateral objective cochlear tinnitus

We studied possible brain changes with functional MRI (fMRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) in a patient with a rare, high-intensity "objective tinnitus" (high-level SOAEs) in the left ear of 10 years duration, with no associated hearing loss. This is the first case of objective cochlear tinnitus to be investigated with functional neuroimaging. The objective cochlear tinnitus was measured by Spontaneous Otoacoustic Emissions (SOAE) equipment (frequency 9689 Hz, intensity 57 dB SPL) and is clearly audible to anyone standing near the patient. Functional modifications in primary auditory areas and other brain regions were evaluated using 3T and 7T fMRI and FDG-PET. In the fMRI evaluations, a saturation of the auditory cortex at the tinnitus frequency was observed, but the global cortical tonotopic organization remained intact when compared to the results of fMRI of healthy subjects. The FDG-PET showed no evidence of an increase or decrease of activity in the auditory cortices or in the limbic system as compared to normal subjects. In this patient with high-intensity objective cochlear tinnitus, fMRI and FDG-PET showed no significant brain reorganization in auditory areas and/or in the limbic system, as reported in the literature in patients with chronic subjective tinnitus.

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.

2014

High-field functional MRI (7 Tesla) mapping of Tonotopy in Human primary auditory cortex in patients with unilateral hearing loss and 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. Recent studies in mouse models have alleviated tinnitus symptom by reversing plastic reorganization observed in the tonotopic maps of primary auditory cortex (A1) (Engineer et al. Nature, 2011, Yang et al. PNAS 2011). Here, we use high-resolution functional MRI at 7 Tesla (1.5 mm isotropic voxels) to test whether human tinnitus sufferers also have similar disorganization within the auditory cortical maps. Our fMRI mapping paradigm (Da Costa et al. J Neurosci 2011) allows fine-scale imaging of two primary tonotopic maps in human cortex corresponding to regions A1 and R. 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 first finding is that orderly tonotopic maps were seen bilaterally in all patients similar to control subjects, suggesting that unilateral hearing loss with tinnitus does not result in gross distortions of cortical tonotopic organization. Second, we find a tendency for larger response amplitudes in response to low-to-middle frequency tones in patients compared to controls. This result is similar to that observed in the above-mentioned animal studies and was most apparent in those patients with the strongest tinnitus severity (Tinnitus Handicap Inventory). The results suggest that unilateral hearing loss with tinnitus is associated with neural hyper-excitability in human primary auditory cortex. Reduction of this hyper- excitability may be important to the development of treatments to cure tinnitus in humans.

2014

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-field functional MRI (7 Tesla) mapping of Tonotopy in Human primary auditory cortex in patients with unilateral hearing loss and tinnitus.

Naghmeh Ghazaleh, Melissa Saenz, Wietske Van der Zwaag

2014

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

Naghmeh Ghazaleh, Melissa Saenz, Wietske Van der Zwaag

2014

Neuroimaging of human auditory cortex

Naghmeh Ghazaleh

EPFL2017