Spatial Memory and Hippocampal Volume in Humans With Unilateral Vestibular Deafferentation Katharina Hu ¨ fner, 1 * Derek A. Hamilton, 2 Roger Kalla, 1 Thomas Stephan, 1 Stefan Glasauer, 1,3 Jun Ma, 4 Roland Bru ¨ ning, 4 Hans J. Markowitsch, 5 Kirsten Labudda, 5 Christian Schichor, 6 Michael Strupp, 1 and Thomas Brandt 1,3 ABSTRACT: Patients with acquired chronic bilateral vestibular loss were recently found to have a significant impairment in spatial mem- ory and navigation when tested with a virtual Morris water task. These deficits were associated with selective and bilateral atrophy of the hippocampus, which suggests that spatial memory and navigation also rely on vestibular input. In the present study 16 patients with unilateral vestibular deafferentation due to acoustic neurinoma were examined 5- to 13-yrs post-surgery. Volumetry of the hippocampus was performed in patients and age- and sex-matched healthy controls by manually tracing the structure and by an evaluator-independent voxel-based morphometry. Spatial memory and navigation were assessed with a virtual Morris water task. No significant deficits in spatial memory and navigation could be demonstrated in the patients with left vestibular failure, whereas patients with right vestibular loss showed a tendency to perform worse on the respective tests. Impairment was significant only for one computed measure (heading error). The subtle deficiencies with right vestibular loss are com- patible with the recently described dominance of the right labyrinth and the vestibular cortex in the right hemisphere. Volumetry did not reveal any atrophy of the hippocampus in either patient group. V V C 2007 Wiley-Liss, Inc. KEY WORDS: hippocampus; navigation; unilateral vestibular deaf- ferentation; vestibular system INTRODUCTION The human hippocampal formation is known to have an important function in various aspects of memory, such as early encoding, consolidation, and retrieval (Scoville and Milner, 1957; Manns et al., 2003a,b). Several studies in patients with hippocampal lesions have demonstrated its role in spatial memory, that is, remembering where a location is and how to get there (Smith and Milner, 1981; Maguire et al., 1996; Kessels et al., 2001; Spiers et al., 2001; Astur et al., 2002). These findings were confirmed in healthy volunteers by imaging techniques (PET and fMRI) that showed activation, especially of the right hippocampus, during the imagination of navigation (Ghaem et al., 1997; Maguire et al., 1997), as well as wayfinding in a virtual environment, a navigation task defined as ‘‘finding novel paths between locations’’ (Maguire et al., 1998; Gron et al., 2000; Hartley et al., 2003). The ability of an individual to accurately navigate in space is thought to also depend on vestibular input (Etienne, 1980; Matthews et al., 1989; Stackman et al., 2002a; Horii et al., 2004). This concept is sup- ported by studies demonstrating that vestibular stimu- lation in the absence of vision modulates hippocampal neuronal activity in rats (Gavrilov et al., 1995, 1998) and primates (O’Mara et al., 1994). Various anatomi- cal connections have been proposed to exist between the vestibular nuclei and the hippocampus: the tha- lamo-cortical route passing through the thalamus, the parietal cortex, and the ento- or perirhinal cortex to the hippocampus; the u-generating pathway leading from the pontine reticular formation via the supra- mammillary nucleus and medial septum to the hippo- campus; or the head-direction system passing through the dorsal tegmental nucleus, lateral mammillary nu- cleus, and anterodorsal thalamic nucleus to the hippo- campus (for an overview: Smith, 1997; Bland and Oddie, 1998; Russell et al., 2003b; Hopkins, 2005; Smith et al., 2005). Many of these polysynaptic con- nective pathways suggest a bilateral representation of vestibular signals in the hippocampus of rodents (Cuthbert et al., 2000; Zheng et al., 2003). In humans fMRI studies have provided evidence for hip- 1 Department of Neurology, Ludwig-Maximilians University, Munich, Germany; 2 Department of Psychology, University of New Mexico, Albu- querque, New Mexico; 3 Bernstein Center for Computational Neuro- science, Munich, Germany; 4 Department of Neuroradiology, Ludwig- Maximilians University, Munich, Germany; 5 Department of Physiologi- cal Psychology, University of Bielefeld, Bielefeld, Germany; 6 Depart- ment of Neurosurgery, Ludwig-Maximilians University, Munich, Germany Grant sponsor: BMBF; Grant number: BCCN Munich 01GQ0440. Abbreviations used: ANOVA, analysis of variance; ANCOVA, analysis of covariance; BVD, bilateral vestibular deafferentation; CSF, cerebrospinal fluid; HPC, hippocampus; UVD, unilateral vestibular deafferentation; VBM, voxel-based morphometry; VMWT, virtual Morris water task. Jun Ma is currently at Department of Neuroradiology, Tiantan Hospital, Beijing, China. Roland Bru ¨ ning is currently at Department of Radiology, Asklepios Klinik Barmbek, Hamburg, Germany. *Correspondence to: Katharina Hu ¨ fner, MD, Department of Neurology, Ludwig-Maximilians University, Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany. E-mail: katharina.huefner@med.uni-muenchen.de Accepted for publication 13 February 2007 DOI 10.1002/hipo.20283 Published online 30 March 2007 in Wiley InterScience (www.interscience. wiley.com). HIPPOCAMPUS 17:471–485 (2007) V V C 2007 WILEY-LISS, INC.