Sound level dependence of the primary auditory cortex: Simultaneous measurement with 61-channel EEG and fMRI

Abstract

Sound level dependence has been investigated for years with event-related potentials (ERP). A serotonergic modulation of the sound level dependence only of the primary auditory cortex but not of the auditory association cortex has been suggested by a number of clinical and preclinical studies. Therefore, a precise covering of the activity of the primary auditory cortex seems necessary if sound level dependence is used as an indicator of the central serotonergic system. Recent fMRI studies described a pronounced sound level dependence only in the Heschl gyrus/primary auditory cortex but not in auditory association areas. In the present simultaneous 61-channel EEG and fMRI study investigating fourteen healthy subjects, we found a high correlation between the loudness-dependent change of the extent of fMRI activation (number of activated voxels) and the corresponding changes of the mean current source density within the same region of interest covering the primary auditory cortex (r = 0.84, P < 0.001). Our findings suggest a close relationship between the fMRI signal and event-related potential activity. In addition, the correspondence of the ERP-based data and the fMRI results further supports the validity of the ERP localization approach.

Introduction

A growth in the cortical response with an increase in sound level is a well-known finding since early evoked potential studies almost 40 years ago (Rapin et al., 1966) demonstrated that the amplitude of the main response, measured from the peak of the N1 to the peak of the P2 component, increased progressively with sound level. This loudness dependence of the auditory-evoked potential (LDAEP) has been a common finding in a large number of studies since that early findings (Hegerl et al., 1994, Dierks et al., 1999, Brocke et al., 2000). A major interest for this phenomenon has emerged in psychiatric research since several lines of evidence suggested a serotonergic modulation of the cortical loudness dependence (Hegerl and Juckel, 1993, Hegerl et al., 2001): Since the central serotonergic system plays an important role in the pathophysiology and therapeutic strategies in diseases like depression reliable markers of the serotonergic system are urgently needed.

Direct evidence for a possible relationship between the cortical loudness dependence and the serotonergic system comes from animal studies: Juckel et al. directly manipulated the serotonergic neurons in the dorsal raphe nucleus of the brainstem in behaving cats. Stimulation (microinjection of the 5-HT1A antagonist spiperone) was associated with a decrease of the cortical loudness dependence and inhibition (using the 5-HT1A agonist 8-OH-DPAT) with an increase of the loudness dependence (Juckel et al., 1999). Interestingly, this effect was present only in the primary auditory cortex but not in the auditory association cortex (Juckel et al., 1996, Juckel et al., 1997, Juckel et al., 1999). Further evidence comes from the finding of a positive correlation between the serotonin syndrome scale score and the LDAEP in patients treated with serotonergic drugs (Hegerl et al., 1998). In an interesting study investigating 28 abstinent recreational ecstasy users, an increased loudness dependence was described and interpreted with the hypothesis that abstinent ecstasy users present with diminished central serotonergic activity as a consequence of the neurotoxic potential of ecstasy (Tuchtenhagen et al., 2000).

Recently, a positive correlation between the serotonin transporter availability as assessed with beta-CIT and SPECT and the cortical LDAEP was described (Pogarell et al., 2004). In addition, a significant relationship between the loudness dependence and genes involved in the serotonergic transmission has been found (Gallinat et al., 2003, Strobel et al., 2003).

Tryptophan depletion (to reduce the serotonin content in the human brain) was shown to have a significant influence on the loudness dependence at the contralateral hemisphere (Kahkonen et al., 2002).

In the abovementioned animal studies, a high correlation between manipulation of the activity of serotonergic neurons and loudness dependence was described only for the primary but not for the secondary auditory cortex and also other evidence suggests a high serotonergic innervation only of the primary but not the secondary auditory cortex. Therefore, it is reasonable to separate the evoked activity generated by the primary auditory cortex from the evoked activity generated by the secondary auditory cortex using, e.g., dipole source analysis (Scherg and von Cramon, 1985, Hegerl et al., 1994). Using this approach, a prediction of treatment response to selective serotonin reuptake inhibitors in patients with depression has been demonstrated (Gallinat et al., 2000, Mulert et al., 2002). Following this line we have tried to improve the coverage of the primary auditory cortex using a tomographic approach based on an MRI probability map of the primary auditory cortex and could in fact improve our results (prediction of treatment response) again (Penhune et al., 1996, Mulert et al., 2002).

Intensity dependence of the auditory cortex has been described in the last years increasingly with hemodynamic-based imaging techniques like fMRI (Jancke et al., 1998, Brechmann et al., 2002, Hall et al., 2001). Brechmann and colleagues pointed out that sound level dependence was present mainly in the primary auditory cortex/Heschl gyrus (HG). An investigation of Hart et al. (2003) extended this result in taking both the extent of activation (within a region of interest) as well as the magnitude (mean signal change) into account (Hart et al., 2003). For both measurements, a more distinct sound level dependence was described for the primary auditory cortex in comparison to the “anterior lateral area/ALA” (extending beyond Heschl gyrus to the convexity of the superior temporal gyrus) and the planum temporale (PT).

Since fMRI offers a superior spatial resolution in comparison to ERP-based localization approaches, the present study was primarily intended to compare our tomographic current source density approach based on an MRI probability map of the primary auditory cortex with an fMRI approach using the same region of interest. As fMRI parameter we used extent (number of activated voxels), magnitude (mean-adjusted signal change), as well as the statistical weighted mass in the primary auditory cortex. As ERP parameters, we used the mean current source density in the primary auditory cortex (using the same ROI definition as used for the fMRI analysis) both from a session inside and a session outside the scanner, as well as the N1 peak amplitude of both sessions, as measured at Cz. From a more basic point of view, we were in addition generally interested in which fMRI-based and which ERP-based parameters were related to each other and which were not.