On the role of thalamic pathology in diencephalic amnesia

Although it is now accepted that medial diencephalic lesions can produce severe amnesia in humans, the specific nuclei and neural pathways that must be damaged to impair memory have not yet been identified. Recent studies have shown that pyrithiamine-induced thiamine deficiency (PTD) in the rat can produce a consistent pattern of pathology in the thalamus and mammillary bodies and result in permanent impairments on behavioral measures of working memory. Behavioral deficits comparable to the PTD model have been observed in rats with thalamic lesions involving lateral portions of the internal medullary lamina (the L-IML site). Such impairments are not observed following lesions of limbic-related pathways associated with the fornix, mammillary bodies, or midline thalamus. The L-IML lesion affects the mediodorsal nucleus (MDn) and both the intralaminar and paralaminar non-specific thalamic nuclei. The relationship between the non-specific thalamic nuclei and working memory is underscored by the limited behavioral effects of MDn lesions, as compared to either L-IML or PTD-induced lesions, and by anatomical analyses of PTD-related pathology, which seems to destroy the non-specific nuclei while sparing large portions of the MDn. Recent physiological studies of thalamocortical processes suggest that there are several possible mechanisms by which the non-specific nuclei might participate in memory and by which lesions in these pathways might interfere with the consolidation of memories within the cortex.