Dave R. M. Langers

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.

Tonotopic mapping of human auditory cortex

Since the early days of functional magnetic resonance imaging (fMRI), retinotopic mapping emerged as a powerful and widely-accepted tool, allowing the identification of individual visual cortical fields and furthering the study of visual processing. In contrast, tonotopic mapping in auditory cortex proved more challenging primarily because of the smaller size of auditory cortical fields. The spatial resolution capabilities of fMRI have since advanced, and recent reports from our labs and several others demonstrate the reliability of tonotopic mapping in human auditory cortex. Here we review the wide range of stimulus procedures and analysis methods that have been used to successfully map tonotopy in human auditory cortex. We point out that recent studies provide a remarkably consistent view of human tonotopic organisation, although the interpretation of the maps continues to vary. In particular, there remains controversy over the exact orientation of the primary gradients with respect to Heschls gyrus, which leads to different predictions about the location of human A1, R, and surrounding fields. We discuss the development of this debate and argue that literature is converging towards an interpretation that core fields A1 and R fold across the rostral and caudal banks of Heschls gyrus, with tonotopic gradients laid out in a distinctive V-shaped manner. This suggests an organisation that is largely homologous with non-human primates. This article is part of a Special Issue entitled Human Auditory Neuroimaging.

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).

Enhanced signal detection in neuroimaging by means of regional control of the global false discovery rate

In the context of neuroimaging experiments, it is essential to account for the multiple comparisons problem when thresholding statistical mappings. Various methods are in use to deal with this issue, but they differ in their signal detection power for small- and large-scale effects. In this paper, we comprehensively describe a new method that is based on control of the false discovery rate (FDR). Our method increases sensitivity by exploiting the spatially clustered nature of neuroimaging effects. This is achieved by using a sliding window technique, in which FDR-control is first applied at a regional level. Thus, a new statistical map that is related to the regionally achieved FDR is derived from the available voxelwise P-values. On the basis of receiver operating characteristic (ROC) curves, thresholding based on this map is demonstrated to have better discriminatory power than conventional thresholding based on P-values. Secondly, it is shown that the resulting maps can be thresholded at a level that results in control of the global FDR. By means of statistical arguments and numerical simulations under widely varying conditions, our method is validated, characterized, and compared to some other common voxel-based methods (uncorrected thresholding, Bonferroni correction, and conventional FDR-control). It is found that our method shows considerably higher sensitivity as compared to conventional FDR-control, while still controlling the achieved FDR at the same level or better. Finally, our method is applied to two diverse neuroimaging experiments to assess its practical merits, resulting in substantial improvements as compared to the other methods.

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.

Neuroanatomical abnormalities in chronic tinnitus in the human brain

Highlights • We review brain anatomical studies of tinnitus.• We evaluate the “gating mechanism” in light of the evidence from these studies.• We discuss the results and the possible causes of disparity between findings.• Overall, the evidence for structural abnormalities in tinnitus is unconvincing.• We identify methodological concerns and suggest strategies for future research.

Unilateral Tinnitus: Changes in Connectivity and Response Lateralization Measured with fMRI

Tinnitus is a percept of sound that is not related to an acoustic source outside the body. For many forms of tinnitus, mechanisms in the central nervous system are believed to play a role in the pathology. In this work we specifically assessed possible neural correlates of unilateral tinnitus. Functional magnetic resonance imaging (fMRI) was used to investigate differences in sound-evoked neural activity between controls, subjects with left-sided tinnitus, and subjects with right-sided tinnitus. We assessed connectivity patterns between auditory nuclei and the lateralization of the sound-evoked responses. Interestingly, these response characteristics did not relate to the laterality of tinnitus. The lateralization for left- or right ear stimuli, as expressed in a lateralization index, was considerably smaller in subjects with tinnitus compared to that in controls, reaching significance in the right primary auditory cortex (PAC) and the right inferior colliculus (IC). Reduced functional connectivity between the brainstem and the cortex was observed in subjects with tinnitus. These differences are consistent with two existing models that relate tinnitus to i) changes in the corticothalamic feedback loops or ii) reduced inhibitory effectiveness between the limbic system and the thalamus. The vermis of the cerebellum also responded to monaural sound in subjects with unilateral tinnitus. In contrast, no cerebellar response was observed in control subjects. This suggests the involvement of the vermis of the cerebellum in unilateral tinnitus.

Functional specialization of the male insula during taste perception

The primary gustatory area is located in the insular cortex. Although the insular cortex has been the topic of multiple parcellation studies, its functional specialization regarding taste processing received relatively little attention. Studies investigating the brain response to taste suggested that the insular cortex is involved in processing multiple characteristics of a taste stimulus, such as its quality, intensity, and pleasantness. In the current functional magnetic resonance study, younger and older adult male subjects were exposed to four basic tastes in five increasing concentrations. We applied a data-driven analysis to obtain insular response maps, which showed that the insular cortex processes the presence of taste, its corresponding pleasantness, as well as its concentration. More specifically, the left and right insular cortices are differentially engaged in processing the aforementioned taste characteristics: representations of the presence of a taste stimulus as well as its corresponding pleasantness dominate in the left insular cortex, whereas taste concentration processing dominates in the right insular cortex. These results were similar across both age groups. Our results fit well within previous cytoarchitectural studies and show insular lateralization in processing different aspects of taste stimuli in men.