Vascular thalamic amnesia: A reappraisal

Abstract

In humans lacunar infarcts in the mesial and anterior regions of the thalami are frequently associated with amnesic syndromes. In this review paper, we scrutinized 41 papers published between 1983 and 2009 that provided data on a total of 83 patients with the critical ischemic lesions (i.e. 17 patients with right-sided lesions, 25 with left-sided lesions and 41 with bilateral lesions). We aimed to find answers to the following questions concerning the vascular thalamic amnesia syndrome: (i) Which qualitative pattern of memory impairment (and associated cognitive and behavioral deficits) do these patients present? (ii) Which lesioned intrathalamic structures are primarily responsible for the amnesic syndrome? (iii) Are the recollection and familiarity components of declarative memory underlain by the same or by different thalamic structures? Results of the review indicate that, similar to patients with amnesic syndromes due to mesio-temporal lobe damage, patients with vascular thalamic amnesia display a prevalent deficit of declarative anterograde long-term memory, a less consistent deficit of declarative retrograde long-term memory and substantially spared short-term and implicit memory. Unlike mesio-temporal lobe patients, however, vascular thalamic amnesics often present dysexecutive and behavioral deficits similar to those observed in patients with frontal damage. The presence of an amnesic syndrome in patients with thalamic lacunar infarcts is strongly predicted by involvement of the mammillo-thalamic tract, which connects the anterior nuclei complex to the hippocampus proper via the fornix and the mammillary bodies. Finally, data reported in a few single cases provide support for the hypothesis that thalamic regions connected to distinct areas of the mesio-temporal lobe play differential roles in recollection and familiarity processes. The mammillo-thalamic tract/anterior nuclei axis seems primarily implicated in recollective processes, whereas the ventroamygdalofugal pathway/medio-dorsal axis primarily underlies familiarity processes.

Introduction

It has been known for a long time that in humans restricted damage to discrete structures of the thalami may be responsible for an amnesic syndrome similar, in many regards, to that observed in patients with hippocampal amnesia (for reviews see Van der Werf et al., 2003, Van der Werf et al., 2000). The role of the thalamus in declarative memory functioning (and the possible emergence of an amnesic syndrome as a consequence of thalamic damage) has been traditionally related to its multiple connections with structures in the mesial temporal lobe (MTL). Based on anatomical data from nonhuman primates, the best-known connection is the one linking the hippocampus proper to the anterior and latero-dorsal nuclei of the thalamus via the fornix, the mammillary bodies (MBs), and the mammillo-thalamic tract (MTT) (Aggleton et al., 1986, Aggleton and Saunders, 1997). A direct (but less rich) connection to the hippocampus consists of fibers that reach the anterior nuclei and the latero-dorsal nucleus directly from the fornix (i.e. without passing through the MBs). Finally, a third neural pathway linking the MTL to the thalamus is the ventroamygdalofugal pathway, which conveys fibers from the amygdala and the perirhinal cortex in the parahippocampal gyrus, enters the thalamus via the inferior thalamic peduncle, and reaches the medio-dorsal (MD) nucleus by passing through the internal medullary lamina (Graff-Radford, Tranel, Van Hoesen, & Brandt, 1990) (Fig. 1).

Two pathological conditions of the thalamus most often give rise to memory disorders. The first is Korsakoff's syndrome, which results from a chronic thiamine deficiency in individuals with malnutrition due to alcoholism or other conditions (for a review, see Kopelman, Thomson, Guerrini, & Marshall, 2009). The second is lacunar infarcts affecting the anterior–mesial regions of the thalami (Van der Werf et al., 2003, Van der Werf et al., 2000). Korsakoff's syndrome provides little information in vivo about the intrathalamic localization of lesions responsible for memory deficits. Neuropathological studies have demonstrated that neuronal loss can be observed in these patients at the level of the MBs and in various thalamic nuclei, most notably in the MD and anterior nuclei complex. Most recent evidence supports a closer relationship between anterior nuclei damage and memory dysfunction (Harding, Halliday, Caine, & Kril, 2000). Until now, however, it has been impossible to localize in vivo the intrathalamic damage in patients with Korsakoff's syndrome. Therefore, the present review will be concerned with cases published so far on thalamic amnesia due to lacunar infarcts of the anterior–mesial regions of the thalami.

For this purpose, we scrutinized the neurological literature for papers reporting individual or multiple cases of patients with unilateral or bilateral infarcts in the thalamic territories supplied by the tuberothalamic and/or paramedian arteries (for anatomical details on the origins and vascular territories of these two arteries, see Schmahmann, 2003). The tuberothalamic artery supplies the anterior region of the thalami, including the MTT, but only marginally supplies the anterior nuclei complex, which is mainly served by branches from the anterior choroidal arteries. Moreover, lacunar infarcts due to tuberothalamic artery occlusions generally involve only a very limited region of the MD nucleus corresponding to its polar–ventral surface. The paramedian artery, instead, supplies a somewhat more posterior and mesial thalamic region, primarily corresponding to the MD and intralaminar nuclei. However, portions of the ventral nuclei complex are also frequently affected. Lacunar infarcts can be unilateral or bilateral, with a variable degree of asymmetry depending on the origin of the two arteries from a distinct or a common trunk of the posterior communicating artery (Schmahmann, 2003).

Three main topics will be considered in this review: (i) first, we will try to delineate the qualitative characteristics of the memory deficit in patients with thalamic amnesia, particularly the kinds of memory affected by the deficit, the material modality of the memory deficit in patients with unilateral stroke, and the presence of other cognitive deficits; (ii) second, we will attempt to clarify which of the intrathalamic structures are usually damaged in patients with thalamic amnesia. We will devote particular attention to the MTT and the MD and intralaminar nuclei; (iii) finally, we will review the neuropsychological evidence to find support for a distinction between deficits selectively affecting the recollection or familiarity components of declarative memory in patients with thalamic amnesia.

With respect to previous reviews on this topic (e.g., Van der Werf et al., 2000), the present one (i) considers a larger sample of patients, and (ii) gives particular emphasis to the recollection/familiarity distinction in the domain of declarative memory deficits, a topic of intense experimental work and theoretical debate in the neuropsychological literature on human memory over the last decade (e.g., Aggleton and Brown, 1999, Eichenbaum et al., 2007, Squire et al., 2007).