Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation

Abstract

The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes.

Significance statement: In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated spatial recall using a virtual environment in two groups of patients with hippocampal damage (moderate/severe) and a normal control group. The results showed that patients with severe hippocampal damage are impaired in learning and recalling allocentric spatial information. Furthermore, hippocampal volume reduction impaired allocentric navigation beyond what can be predicted by memory quotient as a widely used measure of general memory function.

Keywords: amnesia; human; memory; navigation; spatial; virtual reality.

Figure 1.

Age, IQ, and MQ for the three experimental groups. On each box: Horizontal red line indicates the median. Edges of the box indicate the 25th (q1) and 75th (q3) percentiles. Whiskers extend to the most extreme data points not considered outliers. Points are considered outliers (displayed as a red +) if they are larger than q3 + (q3 − q1) or smaller than q1 − (q3 − q1). *p < 0.01, patient groups compared with the control group (t test). **p < 0.001, patient groups compared with the control group (t test).

Figure 2.

Percentage volume reduction relative to the control group mean. Box properties are the same as in Figure 1. Positive values correspond to volumes smaller than the control group mean. *p < 0.01, patient groups compared with the control group (t test). **p < 0.001, patient groups compared with the control group (t test). Hip, Hippocampus; Thal, thalamus; Put, putamen; Pall, pallidum; NAcc, nucleus accumbens; caud, caudate nucleus.

Figure 3.

K-means cluster analysis separates patients with SHD from controls and from patients with MHD. Boundary errors, as well as landmark errors, were normalized across groups between 0 and 1. Two clusters were separable: one consisting mainly of patients with SHD and the other consisting exclusively of controls and those with MHD. Top and right margins represent normal distributions fit to the resulting clusters.

Figure 4.

Canonical correlation analysis between volume measures (black) and memory measures (white) across experimental groups. b-error and l-error are expressed as 1/(boundary error) and 1/(landmark error), respectively (this is different from Fig. 3), to match the sign of the spatial memory measures with that of MQ (larger values reflecting better performance). Individual variables were centered and scaled. Top, The canonical coefficients reflect the weighted contribution of the individual variables, in the presence of each other, to the canonical correlation. Bottom, Correlation coefficients between the individual variables and the canonical variables. **p < 0.001; all other p > 0.01. Hip, Hippocampus; Thal, thalamus; Put, putamen; Pall, pallidum; NAcc, nucleus accumbens; caud, caudate nucleus; b-error, boundary error; l-error, landmark error.

Figure 5.

Learning data. Patients with MHD and control participants improve recall performance (i.e., lower the distance error) as a function of block. Patients with SHD exhibit poorer recall performance and do not improve as a function of block.