Elsevier

NeuroImage

Volume 61, Issue 4, 16 July 2012, Pages 978-986
NeuroImage

High fidelity tonotopic mapping using swept source functional magnetic resonance imaging

https://doi.org/10.1016/j.neuroimage.2012.03.031Get rights and content

Abstract

Tonotopy, the topographic encoding of sound frequency, is the fundamental property of the auditory system. Invasive techniques lack the spatial coverage or frequency resolution to rigorously investigate tonotopy. Conventional auditory fMRI is corrupted by significant image distortion, sporadic acoustic noise and inadequate frequency resolution. We developed an efficient and high fidelity auditory fMRI method that integrates continuous frequency sweeping stimulus, distortion free MRI sequence with stable scanner noise and Fourier analysis. We demonstrated this swept source imaging (SSI) in the rat inferior colliculus and obtained tonotopic maps with ~ 2 kHz resolution and 40 kHz bandwidth. The results were vastly superior to those obtained by conventional fMRI mapping approach and in excellent agreement with invasive findings. We applied SSI to examine tonotopic injury following developmental noise exposure and observed that the tonotopic organization was significantly disrupted. With SSI, we also observed the subtle effects of sound pressure level on tonotopic maps, reflecting the complex neuronal responses associated with asymmetric tuning curves. This in vivo and noninvasive technique will greatly facilitate future investigation of tonotopic plasticity and disorders and auditory information processing. SSI can also be adapted to study topographic organization in other sensory systems such as retinotopy and somatotopy.

Highlights

► We developed an efficient swept source imaging (SSI) fMRI for tonotopic mapping. ► SSI integrates continuous frequency sweeping, bSSFP sequence and Fourier analysis. ► High resolution tonotopic mapping using SSI is demonstrated in inferior colliculus. ► Tonotopic injury following developmental noise exposure is studied using SSI. ► Varying sound pressure level allows SSI to probe local auditory neuronal response.

Introduction

Humans and many animal species rely on effective hearing to survive and prosper in a competitive world. The sense of hearing and the auditory system that processes acoustic information are critical for performing core functions such as communicating, finding food and avoiding danger. The auditory system is very adept at distinguishing among frequency components in a sound, which allows us to hear the fine differences in words and allows animals to distinguish the sounds of predators and prey. For example, humans can distinguish two pure tone sounds that differ by only 2 to 6 Hz even though the sounds are in the frequency range of 1 to 4 kHz (Longstaff, 2005, Malmierca et al., 2009). To enhance our abilities to perform these vital functions or to treat auditory disorders such as tinnitus (Muhlnickel et al., 1998) that reduce quality of life, we need to advance our understanding of frequency encoding in the auditory system.

Much of our knowledge of auditory function and frequency encoding comes from invasive studies (Ehret and Fischer, 1991). Sound pressure waves enter the ear and vibrate the ear drum. These vibrations are transmitted to the basilar membrane, whose motions produce periodic depolarization and hyperpolarization of hair cells (Longstaff, 2005), sending neuronal signals to the cochlear nucleus of the central auditory pathway. Axons carrying neuronal signals run from the cochlear nucleus to the superior olivary complex, then the lateral lemniscus, inferior colliculus (IC), medial geniculate body and the auditory cortex (Malmierca, 2003). At each structure of the auditory pathway, electrophysiology studies have observed that the majority of neurons have sharp frequency tuning curves, meaning these neurons are most sensitive to a narrow spectrum of sounds centered about a characteristic frequency (CF).

The findings of invasive electrophysiology and immunohistochemistry studies also suggest that neurons in a structure with similar CFs are positioned close together (Ehret and Fischer, 1991). This indicates the presence of tonotopic organization, a topographic encoding of frequency. The ideal technique for studying tonotopy would be sensitive to neuronal activity and be capable of mapping a large field of view (FOV) with high spatial and frequency resolution. Unfortunately, the traditional techniques are not ideal. Electrophysiological recordings cannot achieve the continuous spatial coverage and large FOV needed to thoroughly study tonotopy. Immunohistochemistry techniques would require an infeasible number of animals to cover a broad frequency range and are difficult to use, if not inapplicable, in longitudinal investigations.

Functional magnetic resonance imaging (fMRI) has potential for tonotopic mapping. fMRI using the blood oxygenation level-dependent (BOLD) signal for endogenous contrast is widely used in brain mapping (Bilecen et al., 1998b, Cheung et al., 2012, Ogawa et al., 1990). BOLD fMRI is noninvasive and applicable to longitudinal human and animal studies. It is typically implemented with echo planar imaging (EPI) sequences, which provide adequately high spatial resolution (~ 1 mm in clinical scanners). However, EPI emits sporadic acoustic noise which adversely affects auditory fMRI (Seifritz et al., 2006). Auditory studies typically employ sparse temporal sampling paradigms, which use EPI sequences with long repetition time (on the order of 10 s), to reduce the adverse effects of scanner noise (Hall et al., 1999). This technique has proven useful, but it is highly time inefficient and like conventional EPI, images suffer from distortion and susceptibility induced signal loss (Jezzard and Balaban, 1995), which hamper studies in many fine structures in the auditory system. These limitations become more apparent at high magnetic fields and will restrain the growth of high resolution auditory fMRI.

Stimulation in fMRI tonotopy studies is typically presented in block-design paradigms (Baumann et al., 2011, Bilecen et al., 1998a). Block-design involves presenting a pure tone sound to the subject in an on–off pattern and using statistical analysis to identify brain regions where the BOLD signal correlates with the stimulus on–off timing. Recently, we applied a block-design paradigm to map tonotopic organization in the rat IC and map the ascending auditory pathway (Cheung et al., 2012). Block-design provides high statistical power and sensitivity. However, it cannot map tonotopic organization with high frequency resolution as only a limited number of pure tones can be presented in a study session. All together, the conventional fMRI techniques for tonotopic mapping using EPI and block-design suffer from image distortion, signal loss and low frequency resolution.

We develop a novel fMRI technique named magnetic resonance swept source imaging (SSI) that maps the tonotopic organization of auditory structures with high spectral and spatial resolution. Instead of EPI, SSI uses balanced steady state free precession (bSSFP), a fast MRI acquisition sequence that provides T2/T1 contrast without sparse temporal sampling (Lee et al., 2008, Zhou et al., in press), image distortion, susceptibility-induced signal loss and sporadic noise. Therefore, bSSFP avoids the time inefficiencies and image artifacts of EPI and is ideally suited for auditory fMRI studies. To improve upon block-design, SSI uses a frequency sweeping stimulation paradigm along with Fourier transformation analysis that maps tonotopic organization over a continuous frequency spectrum.

In this study, we first describe SSI and demonstrate its ability to map tonotopy in the rat IC. In normal animals, the new tonotopic maps show significantly higher frequency resolution and spatial fidelity compared with conventional fMRI maps. We subsequently apply SSI to study the IC of animals injured by early post-natal noise exposure (NE) and find that the tonotopic organization is significantly disrupted. We also observe with SSI the subtle effects of sound pressure level (SPL) on tonotopic maps, reflecting the neuronal responses associated with asymmetric tuning curves.

Section snippets

Methods

All animal experiments were approved by the local animal research ethics committee. Four different fMRI experiments were performed in this study: (1) mapping inferior colliculus tonotopy in normal animals with magnetic resonance swept source imaging; (2) studying the effect of increasing stimulus sound pressure level on the BOLD signal amplitude; (3) mapping tonotopic changes caused by early post-natal noise exposure; and (4) studying the effect of SPL on observed tonotopic maps. This section

Results

The findings of this study are organized according to the four experiments described in the Methods section.

Discussion

Swept source imaging mapped tonotopy with high fidelity at approximately 2 kHz resolution and 40 kHz bandwidth in 30 min. The resulting tonotopic maps from each animal yielded significantly higher frequency resolution and spatial specificity compared with maps acquired using conventional fMRI and were in excellent agreement with previous invasive findings (Huang and Fex, 1986, Webster et al., 1984). Using SSI, we observed that early post-natal noise exposure significantly disrupted the tonotopic

Acknowledgments

This work was supported by Hong Kong Research Grants Council (General research grants HKU7826/10M and HKU7837/11M to E.X.W.).

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    Authors Matthew M. Cheung and Condon Lau contributed equally to this work.

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