Also, the region identified in figure 1B in the report as the left tail of the caudate is in fact in the corona radiata as it converges to form the internal capsule. This region lies between the caudate and the insula, according to the MRI depiction and the Talairach coordinates given in the report. It could be argued that the proximity to the caudate is within the spatial resolution limits of the method, but if so, then consideration should be given to interpretation of the data as activation of the insula.

Itzhak Fried
Division of Neurosurgery,
University of California School of Medicine
Los Angeles, CA 90095-7039, USA
E-mail: fried{at}surgery.medsch.ucla.edu

REFERENCES

1. E. A. Maguire, et al., Science 280, 921 (1998) [Abstract/Free Full Text] .
2. J. O'Keefe and J. Dostrovsky, Brain Res. 34, 171 (1971) [CrossRef] [ISI] [Medline] .
3. J. Talairach and P. Tournoux, Co-Planar Stereotaxic Atlas of the Human Brain (Thieme, Stuttgart, Germany, 1988).
4. G. K. Aguirre, J. A. Detre, D. C. Alsop, M. D'Esposito, Cerebral Cortex 6, 823 (1996).
5. G. K. Aguirre and M. D'Esposito, J. Neurosci. 17, 2512 (1997).
6. R. Epstein and N. Kanwisher, Nature 392, 598 (1998) [CrossRef] [Medline] .
7. S. Zola-Morgan, L. Squire, S. Ramus, Hippocampus 4, 483 (1994) [CrossRef] [ISI] [Medline] .

Response: Fried raises two issues: the loca- tion of the hippocampal activations reported in our report (1) in relation to the Talairach and Tournoux (2) brain, and the location of the hippocampal activations on the figures as shown in our report. While the Talairach and Tournoux x, y, and z coordinate system was used to locate the voxels of peak activation in our study, the Talairach and Tournoux brain was not. Instead, the scans of volunteers' brains were normalized with reference to the Montreal Neurological Institute's (MNI) template brain (3) (based on 305 normal brains), as we describe in note 7 of our report (1). These brains are different, with the Talairach and Tournoux brain being smaller and less precisely characterized as compared with the MNI template. Thus, although our locations of peak activation are within the hippocampal formation when correctly referenced to the MNI template (CA1 or subiculum, Fig. 1), if inappropriately plotted on the smaller Talairach and Tournoux brain, they appear to be extra-hippocampal.

We appreciate Fried's concern about the lack of clarity afforded by displaying activations on a structural image averaged across the ten subjects, where medial temporal structures are difficult to visualize. Nevertheless, the peak activations as shown on the MNI template brain can be observed in the right hippocampal formation (Fig. 1). In the case of both activations, our discussion was focused on the location of the peaks of activity. In the case of the categorical comparison (successful navigation-arrows), the spread of the activation undoubtedly includes parahippocampal cortex as Fried suggests; however, the peak is in the hippocampal formation. In the case of the correlation between accuracy of navigation and rCBF, the activation remains within the hippocampal formation. Finally, the activations we reported (1) were definitely in the hippocampal formation as compared with the activation observed by Epstein and Kanwisher (4) that Fried mentions. The activation they observed in their study (4)--which called for volunteers to perform a passive, 2-dimensional scenes task--was at least 3 cm posterior in the brain to the activation that we observed (1) while our volunteers performed an active, 3-dimensional navigation task.

Eleanor A. Maguire^*
Wellcome Department of Cognitive Neurology,
Institute of Neurology,
University College London,
12 Queen Square,
London WC1N 3BG, United Kingdom
E-mail: emaguire{at}fil.ion.ucl.ac.uk

REFERENCES AND NOTES

1. E. A. Maguire, et al., Science 280, 921 (1998) .
2. J. Talairach and P. Tournoux, Co-Planar Stereotaxic Atlas of the Human Brain (Thieme, Stuttgart, Germany, 1988).
3. A. C. Evans et al., in Proceedings of the IEEE-Nuclear Science Symposium and Medical Imaging Conference, San Francisco, CA, 31 October to 6 November 1993, L. A. Klaisner, Ed. (Institute of Electrical and Electronics Engineers, Piscataway, NJ, 1993), pp. 1813-1817.
4. R. Epstein and N. Kanwisher, Nature 392, 598 (1998) .