Full Length ArticleBOLD fMRI investigation of the rat auditory pathway and tonotopic organization
Highlights
► fMRI without sparse temporal sampling is used to study the rat auditory system. ► Monaural acoustic stimulation activates multiple cortical and subcortical structures. ► IC and CN BOLD signal changes increase monotonically with SPL. ► In vivo tonotopic mapping using BOLD is demonstrated in inferior colliculus.
Introduction
The ascending auditory pathway traverses multiple major nuclei before reaching the auditory cortex (Malmierca and Merchan, 2004). Hair cells in the ear conduct the mechanical movements of fluid into electrical signals that are transmitted to the cochlear nucleus (CN). The superior olivary complex (SOC) receives most of the projections from CN and projects to the contralateral central nucleus of the inferior colliculus (IC) via the lateral lemniscus (LL). As the largest auditory subcortical nucleus, the IC has diverse connections with every auditory structure and is a relay center for all ascending projections to the thalamus (Winer and Schreiner, 2004). The IC integrates information from the CN and SOC before projecting to the thalamus and the cortex. The medial geniculate body (MGB) in the thalamus receives projections from the IC and projects to different parts of the auditory cortex (AC). Much of our knowledge of the auditory pathway has been acquired with conventional invasive techniques, which are sensitive and provide high spatial resolution, but lack the field of view (FOV) needed to assess the entire brain in a feasible time period. Most studies using invasive techniques such as immunohistochemistry (Yang et al., 2005) and electrophysiology (Goldberg and Brown, 1968) focus on particular structures along the pathway. Recently, large FOV manganese-enhanced magnetic resonance imaging (MEMRI) was used to trace the auditory pathway (Watanabe et al., 2008, Yu et al., 2005). However, manganese is toxic and MEMRI requires prolonged sound stimulation, which hinder longitudinal studies (Van der Linden et al., 2009).
Most neurons along the central auditory pathway, especially in the IC, have the prominent feature of being most sensitive to a characteristic frequency (CF). Cells with similar CF are positioned close together and this structural arrangement is known as tonotopy. Disorders in tonotopic representation could lead to difficulties in pitch perception and voice interpretation (Oxenham et al., 2004). Our understanding of tonotopic organization has come primarily from invasive techniques such as electrophysiology (Clopton and Winfield, 1973, Malmierca et al., 2008), immunohistochemical assay (Ehret and Fischer, 1991, Pierson and Snyder-Keller, 1994) and 2-deoxyglucose labeling (Huang and Fex, 1986). However, these techniques either lack the imaging capabilities to thoroughly study tonotopy or require a large number of animals to study multiple frequencies.
A noninvasive functional imaging technique with large FOV would be valuable for understanding the complex functional organization of the auditory system and developing treatments for hearing impairments. Functional magnetic resonance imaging (fMRI) can be used to measure the hemodynamic response in the entire brain with relatively high temporal and spatial resolution. Numerous task-based brain mapping studies have been performed using blood oxygenation level-dependent (BOLD) fMRI (Ogawa et al., 1998). The major limitation of applying fMRI in hearing studies is the loud acoustic scanner noise. The rapidly switching readout gradients in fMRI produce intense noise and bring adverse effects such as complicating the BOLD response and decreasing its dynamic range (Bandettini et al., 1998, Moelker and Pattynama, 2003). Various techniques have been suggested to reduce the unfavorable effect of acoustic noise. These include modifying the stimulation paradigm to have sparse temporal sampling (Hall et al., 1999), which significantly lengthens scan time but can potentially strengthen responses (Petkov et al., 2009). Nevertheless, continuous scanning still offers advantages over sparse temporal sampling due to its superior temporal resolution and faster acquisition (Petkov et al., 2009). It is often used in combination with passive noise attenuation hardware such as ear muffs or active noise reduction techniques (Goldman et al., 1989). Reliable BOLD responses were previously reported in fMRI studies using continuous scanning (Binder et al., 1994, Tanji et al., 2010).
Primary and secondary auditory cortex activations can be consistently observed in humans by fMRI. Recording subcortical activation is considerably more challenging (Guimaraes et al., 1998, Hesselmann et al., 2001, Yetkin et al., 2004). The challenges include the small size of subcortical structures in humans and imaging artifacts related to cardiac pulsation and susceptibility gradients (Di Salle et al., 2003). Rodent studies are therefore valuable in fMRI investigations of auditory function because the rodent subcortex occupies a significantly larger portion of the brain compared with humans (Glendenning and Masterton, 1998). Rats are a commonly used animal model that shares general anatomical, physiological and behavioral features in the central auditory system with humans and has proven useful in hearing studies (Malmierca and Merchan, 2004). Compared with human auditory fMRI studies, animal fMRI studies (Baumann et al., 2011, Boumans et al., 2007, Boumans et al., 2008, Petkov et al., 2009, Tanji et al., 2010, Van Meir et al., 2005, Yu et al., 2009) have just begun. The results from these studies suggest that auditory fMRI on animals can provide insights into hearing mechanisms.
In this study, we investigate (1) the entire rat auditory pathway and (2) the tonotopic organization of the IC using monaural stimulation and BOLD fMRI. The work represents the first fMRI study of the rodent auditory pathway.
Section snippets
Animal preparation
Animals were prepared for fMRI sessions as described in earlier studies (Chan et al., 2010, Lau et al., 2011a, Lau et al., 2011b). All aspects of this study were approved by the local animal ethics committee. Normal male Sprague–Dawley rats (n = 8, 230 to 280 g) were anesthetized with 3% isoflurane. Controlled dosages were provided by an isoflurane vaporizer (SurgiVet). Anesthesia was maintained with 1% isoflurane throughout the course of setup and MR scanning. Animals were placed in the prone
Results
The recorded power spectra of the scanner room and scanner room + EPI noises are displayed in Fig. 1a. The EPI noise spectrum peaks at 4.7 kHz. Fig. 1b shows the power spectra of the broadband stimulus (auditory pathway study) and the three pure tone stimuli (tonotopy study). For all three pure tones, the harmonics are at least 30 dB lower than the base frequency and therefore, are unlikely to interfere with tonotopic mapping.
Fig. 2a shows the slice localization used in the auditory pathway study.
Discussion
BOLD fMRI with broadband acoustic stimulation reveals activation throughout the rodent auditory pathway. The activated structures include the cochlear nucleus, superior olivary complex, lateral lemniscus, inferior colliculus, medial geniculate body, and auditory cortex. In the CN and IC, the BOLD signal change increases linearly with stimulus SPL. Three frequencies of pure tone stimuli identify the tonotopic organization in the IC. Low frequencies are encoded in the dorsolateral IC and high
Conclusions
The present study demonstrates the BOLD activations upon auditory stimulation in the rat auditory pathway. It also demonstrates the first in vivo tonotopic mapping in the rodent IC using pure tone sounds. These in vivo fMRI findings agree well with the previous electrophysiology and immunohistochemistry findings, indicating the feasibility of auditory fMRI in rodent models.
Acknowledgments
This work was supported in part by Hong Kong Research Grants Council (HKU7837/11M).
References (74)
- et al.
Functional MRI of postnatal visual development in normal and hypoxic-ischemic-injured superior colliculi
NeuroImage
(2010) - et al.
Auditory cortical neuron response differences under isoflurane versus pentobarbital anesthesia
Hear. Res.
(2001) - et al.
Tonotopic organization in the inferior colliculus of the rat
Brain Res.
(1973) - et al.
fMRI of the auditory system: understanding the neural basis of auditory gestalt
Magn. Reson. Imaging
(2003) - et al.
Neuronal activity and tonotopy in the auditory system visualized by c-fos gene expression
Brain Res.
(1991) - et al.
Mapping cortical representations of the rodent forepaw and hindpaw with BOLD fMRI reveals two spatial boundaries
NeuroImage
(2011) ON and OFF components of the auditory brainstem response have different frequency- and intensity-specific properties
Hear. Res.
(1985)- et al.
BOLD responses in the superior colliculus and lateral geniculate nucleus of the rat viewing an apparent motion stimulus
NeuroImage
(2011) - et al.
The cytoarchitecture of the inferior colliculus revisited: a common organization of the lateral cortex in rat and cat
Neuroscience
(2008) - et al.
Human auditory cortical mechanisms of sound lateralisation: III. Monaural and binaural shift responses
Hear. Res.
(1994)
Auditory system
The inferior colliculus of the rat: quantitative immunocytochemical study of GABA and glycine
Neuroscience
Modeling of region-specific fMRI BOLD neurovascular response functions in rat brain reveals residual differences that correlate with the differences in regional evoked potentials
NeuroImage
Optimizing the imaging of the monkey auditory cortex: sparse vs. continuous fMRI
Magn. Reson. Imaging
Development of frequency-selective domains in inferior colliculus of normal and neonatally noise-exposed rats
Brain Res.
Development of tonotopy in the inferior colliculus. I. Electrophysiological mapping in house mice
Brain Res. Dev. Brain Res.
Effects of sound level on fMRI activation in human brainstem, thalamic and cortical centers
Hear. Res.
Effect of sound intensity on tonotopic fMRI maps in the unanesthetized monkey
NeuroImage
MRI in small brains displaying extensive plasticity
Trends Neurosci.
Spatiotemporal properties of the BOLD response in the songbirds' auditory circuit during a variety of listening tasks
NeuroImage
Changes in frequency representation in the auditory system of mice with age-related hearing impairment
Brain Res.
Granule cells in the cochlear nucleus sensitive to sound activation detected by Fos protein expression
Neuroscience
3D mapping of somatotopic reorganization with small animal functional MRI
NeuroImage
Changes of single unit activity in the cat's auditory thalamus and cortex associated to different anesthetic conditions
Neurosci. Res.
Functional MRI of brain activation induced by scanner acoustic noise
Magn. Reson. Med.
Orthogonal representation of sound dimensions in the primate midbrain
Nat. Neurosci.
Cortical reorganization after acute unilateral hearing loss traced by fMRI
Neurology
Functional magnetic resonance imaging of human auditory cortex
Ann. Neurol.
Neural representation of spectral and temporal features of song in the auditory forebrain of zebra finches as revealed by functional MRI
Eur. J. Neurosci.
Functional MRI of auditory responses in the zebra finch forebrain reveals a hierarchical organisation based on signal strength but not selectivity
PLoS One
Mapping the body representation in the SI cortex of anesthetized and awake rats
J. Comp. Neurol.
Spectral and intensity coding in the auditory midbrain
Anatomy of the inferior colliculus in rat
Anat. Embryol.
Inferior colliculus: aging and plasticity
Anesthesia changes frequency tuning of neurons in the rat primary auditory cortex
J. Neurophysiol.
Comparative morphometry of mammalian central auditory systems: variation in nuclei and form of the ascending system
Brain Behav. Evol.
Functional organization of the dog superior olivary complex: an anatomical and electrophysiological study
J. Neurophysiol.
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