Lateralization, connectivity and plasticity in the human central auditory system

Abstract

Although it is known that responses in the auditory cortex are evoked predominantly contralateral to the side of stimulation, the lateralization of responses at lower levels in the human central auditory system has hardly been studied. Furthermore, little is known on the functional interactions between the involved processing centers. In this study, functional MRI was performed using sound stimuli of varying left and right intensities. In normal hearing subjects, contralateral activation was consistently detected in the temporal lobe, thalamus and midbrain. Connectivity analyses showed that auditory information crosses to the contralateral side in the lower brainstem followed by ipsilateral signal conduction towards the auditory cortex, similar to the flow of auditory signals in other mammals. In unilaterally deaf subjects, activation was more symmetrical for the cortices but remained contralateral in the midbrain and thalamus. Input connection strengths were different only at cortical levels, and there was no evidence for plastic reorganization at subcortical levels.

Introduction

The structure and function of the central auditory system in humans is still relatively poorly understood as compared to, e.g., the visual and somatosensory systems. The flow of information from the ears to the cortex has been studied intensively in animals using electrophysiological techniques, but because of their invasive nature, similar studies can hardly be performed on humans. Instead, non-invasive techniques like functional magnetic resonance imaging (fMRI) have been used. However, most of these studies are confined to the auditory cortex, and only a minority encompasses the various subcortical processing centers (Backes and van Dijk, 2002, Budd et al., 2003, Giraud et al., 2000, Guimaraes et al., 1998, Hesselmann et al., 2001, Melcher et al., 2000, Yetkin et al., 2004).

The anatomical structure of the central auditory system is outlined schematically in Fig. 1. It comprises several processing centers that are distributed over the lower brainstem, midbrain, thalamus, and temporal lobes, and that perform extensive spectral and temporal processing (Eggermont, 2001, Ehret and Romand, 1996, Moore, 1991, Nieuwenhuys, 1984, Toga et al., 2000, Yost, 2000). Signals from the stimulated ear first enter the ipsilateral cochlear nucleus via the cochlear nerve to subsequently continue via multiple pathways towards nuclei on both sides of the brain. Binaural information is received first in the superior olivary nuclei and is integrated to construct a representational mapping of the spatial auditory environment in the inferior colliculi. Hereafter, information is transmitted via the medial geniculate nuclei in the thalamus towards the primary auditory cortices in both cerebral hemispheres.

Although the human auditory cortex eventually receives sensory input from both ears, it is excited most strongly by stimulation of the contralateral ear (Lipschutz et al., 2002, Suzuki et al., 2002, Woldorff et al., 1999). However, in unilaterally deaf people cortical activation is known to shift towards a more symmetrical pattern (Bilecen et al., 2000, Ponton et al., 2001, Scheffler et al., 1998, Tschopp et al., 2000). An important issue concerns the extent to which such redistributions reflect processes that occur in the cerebral cortex itself or in subcortical structures. In animal studies, evidence for changes in preferred stimulus lateralization has been demonstrated in the lower brainstem, midbrain and thalamus following unilateral loss of hearing. However, it is yet unclear at what level changes are most prominent, and reports vary from the olivary nuclei and the colliculi to the medial geniculate nuclei (Illing et al., 2000, Kamke et al., 2003, McAlpine et al., 1997, Mossop et al., 2000, Popelar et al., 1994). Moreover, in humans, information regarding the response lateralization at these levels is sparse, and it is yet unknown whether similar shifts exist for the subcortical nuclei in subjects with unilateral deafness.

Changes in response lateralization can presumably be attributed to changes in the strengths of functional relationships between various processing centers. Functional MRI has traditionally been used to localize the structures that are involved in the processing of auditory stimuli with certain characteristics and to determine their response characteristics. However, most studies do not address the relations between the various centers in the processing network. The fact that multiple processing centers respond to a given stimulus supplies evidence that these centers are part of a distributed system, but provides no information on the mutual interactions. To quantify connectivity levels between the involved centers in such a network, correlations between (induced) blood oxygen level-dependent (BOLD) signal fluctuations can be determined (Friston, 1994). Connectivity measures are independent of activation measures in the sense that centers that show significant responses to the same stimuli do not necessarily have to show high levels of connectivity, while centers that show activation to different stimuli potentially can. Connectivity analysis is expected to supplement the information regarding stimulus activation and response lateralization with more insights concerning the signal flow in the central auditory system.

The goal of our study was to investigate the human central auditory system as a whole, using fMRI to characterize the responses in various centers, and to consider the relations between these centers building on prior knowledge gained from animal studies. Auditory stimuli were varied systematically in left and right presentation intensities to determine the lateralization characteristics in both normal hearing and unilaterally deaf subjects.