Pim van Dijk

Representation of lateralization and tonotopy in primary versus secondary human auditory cortex

Functional MRI was performed to investigate differences in the basic functional organization of the primary and secondary auditory cortex regarding preferred stimulus lateralization and frequency. A modified sparse acquisition scheme was used to spatially map the characteristics of the auditory cortex at the level of individual voxels. In the regions of Heschls gyrus and sulcus that correspond with the primary auditory cortex, activation was systematically strongest in response to contralateral stimulation. Contrarily, in the surrounding secondary active regions including the planum polare and the planum temporale, large-scale preferences with respect to stimulus lateralization were absent. Regarding optimal stimulus frequency, low- to high-frequency spatial gradients were discernable along the Heschls gyrus and sulcus in anterolateral to posteromedial direction, especially in the right hemisphere, consistent with the presence of a tonotopic organization in these primary areas. However, in the surrounding activated secondary areas frequency preferences were erratic. Lateralization preferences did not depend on stimulus frequency, and frequency preferences did not depend on stimulus lateralization. While the primary auditory cortex is topographically organized with respect to physical stimulus properties (i.e., lateralization and frequency), such organizational principles are no longer obvious in secondary and higher areas. This suggests a neural re-encoding of sound signals in the transition from primary to secondary areas, possibly in relation to auditory scene analysis and the processing of auditory objects.

Tinnitus does not require macroscopic tonotopic map reorganization

The pathophysiology underlying tinnitus, a hearing disorder characterized by the chronic perception of phantom sound, has been related to aberrant plastic reorganization of the central auditory system. More specifically, tinnitus is thought to involve changes in the tonotopic representation of sound. In the present study we used high-resolution functional magnetic resonance imaging to determine tonotopic maps in the auditory cortex of 20 patients with tinnitus but otherwise near-normal hearing, and compared these to equivalent outcomes from 20 healthy controls with matched hearing thresholds. Using a dedicated experimental paradigm and data-driven analysis techniques, multiple tonotopic gradients could be robustly distinguished in both hemispheres, arranged in a pattern consistent with previous findings. Yet, maps were not found to significantly differ between the two groups in any way. In particular, we found no evidence for an overrepresentation of high sound frequencies, matching the tinnitus pitch. A significant difference in evoked response magnitude was found near the low-frequency tonotopic endpoint on the lateral extreme of left Heschl’s gyrus. Our results suggest that macroscopic tonotopic reorganization in the auditory cortex is not required for the emergence of tinnitus, and is not typical for tinnitus that accompanies normal hearing to mild hearing loss.

Mapping the Tonotopic Organization in Human Auditory Cortex with Minimally Salient Acoustic Stimulation

Despite numerous neuroimaging studies, the tonotopic organization in human auditory cortex is not yet unambiguously established. In this functional magnetic resonance imaging study, 20 subjects were presented with low-level task-irrelevant tones to avoid spread of cortical activation. Data-driven analyses were employed to obtain robust tonotopic maps. Two high-frequency endpoints were situated on the caudal and rostral banks of medial Heschls gyrus, while low-frequency activation peaked on its lateral crest. Based on cortical parcellations, these 2 tonotopic progressions coincide with the primary auditory field (A1) in lateral koniocortex (Kl) and the rostral field (R) in medial koniocortex (Km), which together constitute a core region. Another gradient was found on the planum temporale. Our results show the bilateral existence of 3 tonotopic gradients in angulated orientations, which contrasts with colinear configurations that were suggested before. We argue that our results corroborate and elucidate the apparently contradictory findings in literature.

fMRI activation in relation to sound intensity and loudness

The aim of this fMRI study was to relate cortical fMRI responses to both physical and perceptual sound level characteristics. Besides subjects with normal hearing, subjects with high-frequency sensorineural hearing loss were included, as distortion of loudness perception is a characteristic of such impairment. Cortical responses in both subject groups were analyzed as a function of the physical intensity and the perceived loudness of low and high-frequency stimuli. For the low-frequency stimuli, intensity levels ranged from 0 to 70 dB SL; for the high-frequency stimuli, intensity levels were set such that the corresponding loudness levels matched those of the low-frequency stimuli. Responses were found to increase significantly and predominantly linearly with intensity level and with loudness level. Response saturation at the highest levels was not apparent, but activation exhibited a steep rise between 0 and 10 dB for the low-frequency stimuli. The activation in the subjects with hearing loss increased significantly more strongly with stimulus intensity than that in the normally hearing subjects. This reflects loudness recruitment, characterized by a disproportionate increase in loudness with stimulus intensity. In contrast, the rate of activation increase as a function of loudness level did not differ between both subject groups. This demonstrates that fMRI activation at the level of the auditory cortex is more closely related to the percept of a stimulus (i.e., loudness) rather than to its physical characteristics (i.e., intensity).

A Diffusion Tensor Imaging Study on the Auditory System and Tinnitus

Tinnitus is an auditory percept in the absence of an external sound source. Mechanisms in the central nervous system are believed to be key in the pathophysiology of tinnitus. Diffusion tensor imaging (DTI) is an MR imaging technique that allows in vivo exploration of white matter tissue in the human brain. Using a probabilistic DTI approach, we determined the characteristics of fiber tracts from the inferior colliculus to the medial geniculate body up to the primary auditory cortex. We also investigated the connections between the auditory system and the amygdala, which may be involved in some forms of tinnitus. White matter tracts were characterized by three quantities: the mean fractional anisotropy, the weighted mean fractional anisotropy and the path strength. All these quantities are measures of the patency of white matter tracts. The most important finding is an increased patency of the white matter tracts between the auditory cortex and the amygdala in tinnitus patients as compared to healthy controls.

AMPLITUDE AND FREQUENCY FLUCTUATIONS OF SPONTANEOUS OTOACOUSTIC EMISSIONS

Amplitude and frequency fluctuations of spontaneous otoacoustic emissions have been studied. Spontaneous otoacoustic emissions were recorded from eight human ears and two frog ears (Rana esculenta). Record length typically was 80 s. For a recorded emission signal, the amplitude signal A(t) (average A0) and time intervals T(ti) between successive positive-going zero crossings (i counts zero crossings) were determined. Emission amplitude and period both showed small fluctuations: delta Arms/A0 ranged from 0.7 X 10(-2) to 6.3 X 10(-2) for human emissions and was 24 X 10(-2) for both frog emissions; delta Trms ranged from 1.4 to 6.9 X 10(-7) s for human emission and was 50.0 and 55.0 X 10(-7) s for the two frog emissions. There was a positive correlation between delta Arms/A0 and delta Trms as determined for different emissions (R = 0.9). Spectra of A(t) and T(ti) revealed that amplitude and period were slowly fluctuating functions: cutoff frequency delta f delta A of the amplitude spectrum ranged from 3 to 18 Hz; delta f delta T ranged from 7 to 32 Hz. Results have been compared to amplitude and frequency fluctuations of a second-order oscillator, that interacts with a noise source. It has been concluded that an oscillator with linear stiffness (for example a Van der Pol oscillator) driven by white Gaussian noise, cannot account for all experimental results. Other possible oscillators (e.g., nonlinear stiffness) and noise sources (e.g., narrow-band noise), that may account for the observed phenomena, are discussed.

WIENER KERNEL ANALYSIS OF INNER-EAR FUNCTION IN THE AMERICAN BULLFROG

The response of 17 primary auditory nerve fibers in the American bullfrog (Rana catesbeiana) to acoustic noise stimulation of the tympanic membrane was recorded. For each fiber, the first- and second-order Wiener kernels, k1 (tau 1) and k2 (tau 1, tau 2), were computed by cross correlation of the stimulus and the response. The kernels revealed amplitude and phase characteristics of auditory filters of both phase-locking and non-phase-locking fibers. Wiener kernels of high- and midfrequency fibers (best frequency, BF > 500 Hz), implied a simple sandwich model, consisting of a cascade of a linear bandpass filter, a static nonlinearity, a linear low-pass filter, and a spike generator. The bandpass filter was at least of order 7, and had a linear phase response, for both the high- and the midfrequency fibers. Averaged across fibers, filter order 2, and cutoff frequency 451 Hz for the second filter in the model was observed. The responses of low-frequency fibers (BF < 500 Hz) could not be fit with the sandwich model, because the Fourier transform K2 (f1,f2) of the second-order Wiener kernel showed significant components at off-diagonal frequencies f1 not equal to +/- f2. The presence of these off-diagonal components shows that, in addition to the phase and gain characteristics of auditory filters, the Wiener kernel analysis reveals nonlinear two-tone interactions.

Tinnitus-related dissociation between cortical and subcortical neural activity in humans with mild to moderate sensorineural hearing loss

Tinnitus is a phantom sound percept that is strongly associated with peripheral hearing loss. However, only a fraction of hearing-impaired subjects develops tinnitus. This may be based on differences in the function of the brain between those subjects that develop tinnitus and those that do not. In this study, cortical and sub-cortical sound-evoked brain responses in 34 hearing-impaired chronic tinnitus patients and 19 hearing level-matched controls were studied using 3-T functional magnetic resonance imaging (fMRI). Auditory stimuli were presented to either the left or the right ear at levels of 30-90 dB SPL. We extracted neural activation as a function of sound intensity in eight auditory regions (left and right auditory cortices, medial geniculate bodies, inferior colliculi and cochlear nuclei), the cerebellum and a cinguloparietal task-positive region. The activation correlated positively with the stimulus intensity, and negatively with the hearing threshold. We found no differences between both groups in terms of the magnitude and lateralization of the sound-evoked responses, except for the left medial geniculate body and right cochlear nucleus where activation levels were elevated in the tinnitus subjects. We observed significantly reduced functional connectivity between the inferior colliculi and the auditory cortices in tinnitus patients compared to controls. Our results indicate a failure of thalamic gating in the development of tinnitus.

Distortion product otoacoustic emissions in the tree frog Hyla cinerea

The frog inner ear contains two hearing organs: the amphibian and the basilar papilla. The amphibian papilla is sensitive to low- and mid-frequency stimuli (0.1--0.5 and 0.5--1.3 kHz, respectively, in Hyla cinerea), while the basilar papilla is sensitive to high-frequency stimuli (2.8--3.9 kHz in H. cinerea). Distortion product otoacoustic emissions (DPOAE) were recorded from the ear of the tree frog H. cinerea. In each of six ears investigated, a cubic distortion product (DP) at 2f(1)--f(2) was present when the primary frequencies f(1) and f(2) and the DP frequency were close to either the mid- or the high-frequency range. At frequencies between the sensitive ranges of both papillae, no emissions were observed. For the basilar papilla, the dependence of DP level on the primary tone frequency ratio f(2)/f(1) showed a pattern characteristic of the response of a single nonlinear resonator. Thus, in agreement with neural data, DPOAE from the basilar papilla reflect the contribution of a single auditory filter to emission generation.

The behavior of spontaneous otoacoustic emissions during and after postural changes.

Spontaneous otoacoustic emissions (SOAEs) were studied in humans during and after postural changes. The subjects were tilted from upright to a recumbent position (head down 30 degrees) and upright again in a 6-min period. The SOAEs were recorded continuously and analyzed off-line. The tilting caused a change in the SOAE spectrum for all subjects. Frequency shifts of 10 Hz, together with changes of amplitude (5 dB) and width (5 Hz), were typically observed. However, these changes were observed in both directions (including the appearance and disappearance of emission peaks). The most substantial changes occurred in the frequency region below 2 kHz. An increase of the intracranial pressure, and consequently of the intracochlear fluid pressure, is thought to result in an increased stiffness of the cochlear windows, which is probably mainly responsible for the SOAE changes observed after the downward turn. The time for the spectrum to regain stability after a postural change differed between the two maneuvers: 1 min for the downward and less than 10 s for the upward turn.