Cortical representation of saccular vestibular stimulation: VEMPs in fMRI

Abstract

Short tone bursts trigger a vestibular evoked myogenic potential (VEMP), an inhibitory potential which reflects a component of the vestibulocollic reflex (VCR). These potentials arise as a result of activation of the sacculus and are expressed through the vestibulo-collic reflex (VCR). Up to now, the ascending projections of the sacculus are unknown in humans, only the representation of the semicircular canals or the entire vestibular nerve has been demonstrated. The aim of this study was to determine whether a sacculus stimulus that evoked VEMPs could activate vestibular cortical areas in fMRI.

To determine this, we studied the differential effects of unilateral VEMP stimulation in 21 healthy right-handers in a clinical 1.5 T scanner while wearing piezo electric headphones. A unilateral VEMP stimulus and two auditory control stimuli were given in randomized order over the stimulated ear. A random effects statistical analysis was done with SPM2 (p < 0.05, corrected). After exclusion of the auditory effects, the major findings were as follows: (i) significant activations were located in the multisensory cortical vestibular network within both hemispheres, including the posterior insular cortex, the middle and superior temporal gyri, and the inferior parietal cortex. (ii) The activation pattern was elicited bilaterally with a predominance of the right hemisphere in right-handers. (iii) Saccular vestibular projection was predominantly ipsilateral, whereas (iv) pure acoustic stimuli were processed with a predominance of the respective contralateral and mainly in the left hemisphere.

This is the first demonstration by means of fMRI of the cortical representation of the saccular input at cortical level. The activation pattern is similar to that known from the stimulation of the entire vestibular nerve or the horizontal semicircular canal. Our data give evidence of a task-dependent separation of the processing within the vestibular otolith and the auditory systems in the two hemispheres.

Introduction

Short tone bursts (STB) trigger vestibular evoked myogenic potentials (VEMPs) by saccular stimulation, i.e., inhibitory potentials recorded from the sternocleidomastoid muscle ipsi- and contralaterally which reflect a linear component of the vestibulocollic reflex (VCR) (Colebatch et al., 1994, de Waele, 2001). Its afference is the inferior vestibular nerve (Halmagyi et al., 2005). In this way the saccular otolith of one labyrinth reacts to loud click sounds of 85–130 dB sound pressure level (SPL). To date it is widely accepted that these sounds stimulate only the saccule and not the utricle or the semicircular canals (Halmagyi et al., 2005, McCue and Guinan, 1995, Murofushi and Curthoys, 1997). The VEMPs therefore reflect saccule activation. Up to now, the ascending projections of the sacculus are unknown in humans; only the representation of the semicircular canals or the entire vestibular nerve via the vestibulo-ocular reflex (VOR) had been worked up. Thus, the major goal of the present study was to determine whether a sacculus stimulation with tone bursts that evoked VEMPs could activate vestibular cortical areas via central otolith projections. The only imaging study in which VEMPs were used gave very preliminary data in single subjects, showing an apparent activation pattern in the human fronto-temporal cerebral cortex which was similar to only a small part of that during caloric irrigation (Miyamoto et al., 2005).

Studies in monkeys have identified several separate multisensory areas of the temporo-insular and temporo-parietal cortex by means of multisensory neurons that responded to rotational vestibular as well as optokinetic, somatosensory, and in part visual stimuli (Baloh and Furman, 1989, Büttner and Buettner, 1978, Frederickson et al., 1974, Grüsser et al., 1990a, Ödkvist et al., 1974). However, none of these studies used otolith stimulation. Tracer studies in monkeys have shown that multisensory vestibular areas are closely connected to each other (Akbarian et al., 1994, Guldin and Grüsser, 1996). They include the parieto-insular vestibular cortex (PIVC) in the posterior insula, adjacent retroinsular areas, and the granular insular region (Grüsser et al., 1990b, Guldin and Grüsser, 1996), the visual temporal sylvian area posterior to the PIVC (Guldin and Grüsser, 1998), area 3aV in the central sulcus (Ödkvist et al., 1974), probably area 2v at the tip of the intraparietal sulcus (Frederickson et al., 1974), the periarcuate cortical area 6 pa (Ebata et al., 2004), area 7 in the inferior parietal lobule (Faugier-Grimaud and Ventre, 1989, Ventre and Faugier-Grimaud, 1989), and the ventral intraparietal area (VIP) in the fundus of the intraparietal sulcus (Schlack et al., 2005). On the other hand, little is known on the central representation of linear vestibular stimulation of the vestibular system. Recent findings in non-human primates suggest that integration of visual and vestibular heading signals is achieved by the convergence of both modalities in a dorsal subdivision of the medial superior temporal area (MST) (Fetsch et al., 2007, Gu et al., 2007). MST was formerly thought to only process visual information (optic flow). During the last 10 years several functional imaging studies have revealed that the cortical network in both hemispheres is similar in humans (Bremmer et al., 2001, Fasold et al., 2002, Stephan et al., 2005). These studies used either galvanic stimulation of the entire vestibular nerve (i.e., semicircular canal and otolith fibers) or caloric irrigation of the external ear for vestibular stimulation. Caloric activation activates mainly the horizontal semicircular canal fibers. Areas activated during both types of vestibular stimulation were located in the posterior insula (first and second long insular gyri) and retroinsular regions (representing PIVC and the posterior adjacent visual temporal sylvian area VTS in the monkey (Guldin and Grüsser, 1998)), the superior temporal gyrus, parts of the inferior parietal lobule, the depth of the intraparietal sulcus, the postcentral and precentral gyrus, the anterior insula and adjacent inferior frontal gyrus, the anterior cingulate gyrus, the precuneus and the hippocampus, most often bilaterally.

With respect to this vestibular cortical network the specific questions of the current study were whether short tone bursts that activated the sacculus can elicit activations of cortical areas in humans and, if so, which areas: (i) those of the extrapyramidal motor circuit with the basal ganglia due to involvement of head on trunk coordination in space, (ii) those of the multisensory vestibular cortical network, (iii) only those of the acoustic cortical system, or (iv) a specific combination of the abovementioned areas. If saccular stimulation activates the multisensory vestibular cortex, it would be interesting to determine if this activation is separate and distinct from the entire vestibular nerve stimulation as described above, i.e., if a specific saccular cortical area can be delineated as distinct from cortical areas activated by semicircular canal stimulation.