The neuroanatomical correlates of route learning impairment

Abstract

Recent functional imaging studies of topographical learning point to the participation of a large network of cortical and subcortical regions. Nevertheless, areas which are crucial remain poorly specified due to the absence of group studies of subjects with focal lesions distributed throughout the brain. We assessed the ability of 127 subjects with stable, focal lesions to learn a complex real-life route, a critical aspect of topographical functioning. Results indicated that impairment in route learning was highly associated with damage to medial occipital and posterior parahippocampal cortices in either hemisphere, the right hippocampus, and the right inferotemporal region. Impairment was seen among 86% of the subjects with damage to any these regions, in contrast to impairment among 31% of subjects with lesions in other regions. The importance of medial occipitotemporal cortices bilaterally and right inferotemporal cortex likely reflects the critical role of the ability to quickly and accurately perceive and learn multiple topographical scenes. The importance of the right (and probably left) posterior parahippocampal gyrus and of the right hippocampus likely reflects their critical, distinctive roles forming an integrated representation of the extended topographical environment (i.e., the appearance of places and spatial relationships between specific places), and consolidating that representation into multifaceted contextual knowledge of the environment.

Introduction

Brain damage may result in topographical disorientation (TD), a condition marked by impaired navigation in the real world. TD involves deficits in the abilities to learn the layout and to follow routes to specific destinations in previously unfamiliar environments (i.e., anterograde TD); it may also impair orientation and navigation in environments which had been familiar prior to the onset of brain damage (i.e., retrograde TD). Over the past couple of decades, investigators have most frequently concluded that TD is a consequence of damage or dysfunction of right occipitotemporal cortices ([44], [45], [55], see also [9]), or of right posterior parietal cortex [27], [48], [92].

Uncertainty regarding the neuroanatomical correlates of TD is due to several aspects of the available studies. For one, topographical functioning is an integrated behavioral task requiring multiple cognitive abilities including scene recognition, learning and utilization of spatial-topographical representations, and maintenance of egocentric spatial orientation [3]. Topographical disorientation TD may thus be attributable to defects in one or more distinctive cognitive abilities, defects which may tend to be associated with damage in differing brain regions. However, most investigations of TD have been case studies, which may not reflect the range of associated brain regions. Group studies have been limited by subject selection based on the presence of a specific cognitive deficit (i.e., impaired scene recognition [55]), or by lesion location (i.e., epileptic patients undergoing anterior temporal lobectomy [59]). That process of selection precludes conclusions regarding the range of brain regions that may be associated with impairment in topographical functioning.

Second, in many studies, little attention is paid to the point in a patient’s course at which the patient is evaluated. In particular, in most reported cases of TD following damage affecting the parietal lobe, impairment resolved within the first few months post-onset [9], [18], [92], or there was no assessment beyond the first few months post-onset so that the persistence of TD in the long run was unknown ([9], [53], [89], see also [48]). Thus, there is no clear evidence that circumscribed parietal damage is sufficient to cause chronic TD.

A third problem has been the general lack of attention to the distinction between anterograde and retrograde impairment, and the possibility that their neuroanatomical correlates are not identical. TD case studies have typically focused on retrograde defects, with anterograde defects often mentioned only in passing. However, anterograde TD is important in its own right, as it may be considerably more prevalent than retrograde TD, as evidenced by the fact that patients with retrograde defects invariably have also had marked anterograde defects whenever anterograde functioning was assessed, whereas patients with anterograde defects may or may not have retrograde defects [9]. Furthermore, when both are present, anterograde defects are the more severe, and they tend to persist long after retrograde defects have abated [44], [100].

If the brain regions causing retrograde TD are a subset of those causing anterograde TD, then the selection bias toward reporting cases with retrograde TD may have resulted in an incomplete picture of brain regions important for anterograde topographical functioning. In the few case reports of patients with anterograde TD in the absence of persistent retrograde TD, the locus of lesion is described as right temporal lobe (one patient [28]), right medial occipitotemporal region (two patients [44] — patient no. 1, [84]), right posterior parahippocampal gyrus (one patient [44] — patient no. 2), right medial occipital lobe and left lateral occipital lobe (one patient [81]), and the posterior limb of the right internal capsule (one patient who also showed hypoperfusion of the right parietal region [48]). Taken together, these reports suggest an important contribution by the medial temporal region which is not apparent from the more extensive literature focused on patients with retrograde TD [9]. Indeed, Habib and Sirigu [44], noting that the right posterior parahippocampal gyrus was the site of damage shared by all four of their patients with TD (anterograde or retrograde), speculated that virtually all patients with damage in this region would be found to have topographical impairment if adequately assessed (p. 83).

The possibility that the extant literature might present an incomplete picture of the neuroanatomical correlates of anterograde TD is highlighted by two recent studies. In one, McCarthy et al. [63] described a patient with a striking disturbance of retrograde topographical knowledge but no apparent anterograde deficit following damage to medial and anterior and inferior aspects of the right temporal lobe. However, when anterograde topographical functioning in the real world was assessed with a standardized procedure and compared to normal controls, a significant anterograde defect was documented. That finding is consistent with the observation that standardized assessment of route learning in the real world is more sensitive to subtle deficits than is assessment in simulated environments [8]. The need for standardized assessment in real world situations is further illustrated by the fact that deficits might go undetected when assessed by patient report or clinical observation [34].

In another recent study, Maguire and colleagues [59] assessed topographical learning in right and left temporal lobectomy patients (with resections including varying amounts of the medial temporal region). Subjects viewed several videotaped presentations of locomotion along two overlapping routes through a previously unfamiliar urban neighborhood. Subjects were then assessed on their abilities to map the environment, recognize scenes, and navigate a route through the environment. Both the right and left temporal lobectomy groups were impaired on each of these topographical tasks compared to normal controls. The two patient groups did not differ significantly from each other on any task, although the right temporal group tended to have lower scores on all tasks. Although study subjects did not have clinically significant TD, the finding of impairment associated with anterior temporal lesions on the left as well as the right underscores the need for a group study with systematic assessment of subjects with lesions outside the right posterior region in order to investigate the possible association of topographical impairment with lesions in other brain regions.

The present study was designed to clarify the neuroanatomical correlates of route learning impairment in a large group of subjects with stable, focal brain lesions. As a group, subjects’ lesions were distributed throughout both hemispheres. To ensure that observed deficits reflected stable impairments and not time-limited deficits, subjects were assessed at least 3 months after lesion onset, and approximately 4 years post-onset on average. Their ability to learn a complex route in a real-world environment was assessed, and evaluated in comparison to age-corrected norms. It is emphasized that route learning is but one of two basic aspects of topographical learning, the other being learning of general spatial layout [43]. Subjects were not required to develop a spatial–topographical representation of the environment, so the present study does not bear directly on the ability to learn spatial layout. Three predictions were made. First, it was predicted that lesions in the inferior medial occipital and medial temporal (hippocampus and parahippocampal gyrus) regions of either hemisphere would be associated with route learning impairment. Second, it was predicted that lesions in the posterior parahippocampal gyrus (pPHG) of the right hemisphere would be especially highly associated with route learning impairment. Third, it was predicted that among subjects with lesions in the target regions specified above, unilateral right hemisphere lesions would associated with more frequent and more severe impairment than would unilateral left hemisphere lesions.