The anatomy of amnesia: Neurohistological analysis of three new cases

Abstract

The most useful information about the anatomy of human memory comes from cases where there has been extensive neuropsychological testing followed by detailed post-mortem neurohistological analysis. To our knowledge, only eight such cases have been reported (four with medial temporal lobe damage and four with diencephalic damage). Here we present neuropsychological and post-mortem neurohistological findings for one patient (NC) with bilateral damage to the medial temporal lobe and two patients (MG, PN) with diencephalic damage due to bilateral thalamic infarction and Korsakoff's syndrome, respectively. All three patients exhibited a similar phenotype of amnesia with markedly impaired declarative memory (anterograde and retrograde) but normal performance on tests of nondeclarative memory (e.g., priming and adaptation-level effects) as well as on tests of other cognitive functions. Patient NC had damage to the hippocampus (dentate gyrus and the CA1 and CA3 fields) and layer III of the entorhinal cortex, but with relative sparing of the CA2 field and the subiculum. Patient MG had damage to the internal medullary lamina and mediodorsal thalamic nuclei. Patient PN had damage to the mammillary nuclei, mammillothalamic tracts, and the anterior thalamic nuclei. These findings illuminate several issues regarding the relation between diencephalic and medial temporal lobe amnesia, the status of recognition memory in amnesia, and the neuroanatomy of memory.

Unraveling the contributions of the diencephalon to recognition memory: A review

“…Other relevant evidence comes from the growing appreciation that anterior thalamic atrophy and dysfunction is particularly associated with the memory loss in Korsakoff's syndrome (Harding et al 2000;Gold and Squire 2006). While problems persist concerning the nonspecific nature of the etiology, such findings add to the weight of evidence that these nuclei have an important role in declarative memory.…”

“…As noted above, patients with the amnesic Korsakoff's syndrome all suffer pronounced cell loss in the medial mammillary nucleus (Victor et al 1971;Mair et al 1979;Mayes et al 1988;Gold and Squire 2006), and almost all cases show severely impaired recognition (Aggleton and Shaw 1996). An intriguing exception was a 20-yr-old alcoholic woman diagnosed with Wernicke's disease who had excellent recognition memory yet profound recall (verbal and nonverbal) impairments (Parkin et al 1993).…”

“…Unfortunately, a second stroke just prior to MG's death added to her postmortem pathology, as it caused extensive damage to the right thalamus and right internal capsule. In the left hemisphere, MG's pathology was largely localized in the intralaminar nuclei (paracentral nucleus, central medial nucleus, and central lateral) along with parts of medial dorsal nucleus and the ventral lateral nucleus (Gold and Squire 2006). The implication is that damage to these more posterior thalamic nuclei can impair recognition memory.…”

“…Stroke case MG showed moderate deficits in word and face recognition, associated with bilateral thalamic pathology that was initially determined from MRI scans but then confirmed postmortem (Gold and Squire 2006). Unfortunately, a second stroke just prior to MG's death added to her postmortem pathology, as it caused extensive damage to the right thalamus and right internal capsule.…”

“…All other thalamic nuclei, including the medial dorsal and midline (including parataenial) nuclei, appeared normal (Gold and Squire 2006).…”