Three Cases of Enduring Memory Impairment after Bilateral Damage Limited to the Hippocampal Formation

Abstract

Patient RB (Human amnesia and the medial temporal region: enduring memory impairment following a bilaterial lesion limited to field CA1 of the hippocampus, S. Zola-Morgan, L. R. Squire, and D. G. Amaral, 1986, J Neurosci 6:2950 -2967 was the first reported case of human amnesia in which detailed neuropsychological analyses and detailed postmortem neuropathological analyses demonstrated that damage limited to the hippocampal formation was sufficient to produce anterograde memory impairment. Neuropsychological and postmortem neuropathological findings are described here for three additional amnesic patients with bilateral damage limited to the hippocampal formation. Findings from these patients, taken together with the findings from patient RB and other amnesic patients, make three important points about memory. (1) Bilateral damage limited primarily to the CA1 region of the hippocampal formation is sufficient to produce moderately severe anterograde memory impairment. (2) Bilateral damage beyond the CA1 region, but still limited to the hippocampal formation, can produce more severe anterograde memory impairment. (3) Extensive, temporally graded retrograde amnesia covering 15 years or more can occur after damage limited to the hippocampal formation. Findings from studies with experimental animals are consistent with the findings from amnesic patients. The present results substantiate the idea that severity of memory impairment is dependent on locus and extent of damage within the hippocampal formation and that damage to the hippocampal formation can cause temporally graded retrograde amnesia.

The hippocampal debate: are we asking the right questions?

“…The role of the hippocampus in retrograde amnesia is still under debate [131,143,180] (see Appendix A). As are the specifics of the hippocampal place field parameters (such as the causes for directionality [21,101,174,200,225] and phase precession [16,151,188,208,227]) and the role of the hippocampus in non-spatial tasks (such as contextual conditioning [52,63,65,66,82]).…”

“…After his death, the only damage observable histologically was to the CA1 field of the hippocampus [180,256]. This lab has since reported three additional patients with similar deficits, all with similar histologically-observable damage [180]. DNMS is also impaired by ischemic lesions of rats [248] and monkeys [9].…”

“…showed severe deficits in DNMS-like tasks [256]. After his death, the only damage observable histologically was to the CA1 field of the hippocampus [180,256]. This lab has since reported three additional patients with similar deficits, all with similar histologically-observable damage [180].…”

“…So, although the surgeon's estimates of excised brain clearly indicated extensive damage beyond the hippocampus, it was the hippocampus that Scoville and Milner concentrated on in their case-study report of H.M. [198]. In the subsequent years, declarative memory experiments and models would concentrate on the role of the hippocampus [33,103,104,180,211,212,255].…”

“…they produce graded retrograde amnesia) [33,182,211]. Because H.M. showed what appeared to be graded retrograde amnesia [117,197], and because H.M. was thought to have a hippocampal lesion ( [198], but see [37]), it was thought that hippocampal lesions produced graded retrograde amnesia [33,143,180,211]. The general hypothesis has been that hippocampus stores memories quickly and then replays them for permanent storage in cortex [24,103,104,215].…”