Evaluation of the amnesia caused by restricted thalamic infarcts--6 cases

The amnesic syndrome is analysed in 6 infarctions restricted to the thalamic area. Bilateral lesions were linked to more definite deficits; the anterograde forgetting was unequivocal at the initial stage and affected both verbal and visual memory. In unilateral lesions, deficits were far more discrete and there was no evidence enough for assuming a strict hemispheric specialisation, left for verbal memory, and right for visual memory. These cases and others from the literature suggested that amnesia is more important and pure in infarctions of the anterior part of the thalamus.     

Thalamic Contributions to Anterograde,Retrograde, and Implicit Memory: A Case Study

Learning and memory deficits are typically associated with damage or dysfunction of medial temporal lobe structures; however, diencephalic lesions are another common cause of severe and persistent memory deficits. We focus specifically on the thalamus and review the pathological and neuropsychological characteristics of two common causes of such damage: Korsakoff's syndrome and stroke. We then present a patient who had sustained bilateral medial thalamic infarctions that affected the medial dorsal nucleus and internal medullary lamina. This patient demonstrated the characteristic temporally graded retrograde amnesia and a profound anterograde memory (i.e., explicit memory) deficit within the context of relatively preserved implicit memory. Implications of this explicit–implicit discrepancy are discussed within the context of cognitive rehabilitation techniques that hold promise for more severely impaired patients.     

Anterior Thalamic Inputs Are Required for Subiculum Spatial Coding,with Associated Consequences for Hippocampal Spatial Memory

Just as hippocampal lesions are principally responsible for “temporal lobe” amnesia, lesions affecting the anterior thalamic nuclei seem principally responsible for a similar loss of memory, “diencephalic” amnesia. Compared with the former, the causes of diencephalic amnesia have remained elusive. A potential clue comes from how the two sites are interconnected, as within the hippocampal formation, only the subiculum has direct, reciprocal connections with the anterior thalamic nuclei. We found that both permanent and reversible anterior thalamic nuclei lesions in male rats cause a cessation of subicular spatial signaling, reduce spatial memory performance to chance, but leave hippocampal CA1 place cells largely unaffected. We suggest that a core element of diencephalic amnesia stems from the information loss in hippocampal output regions following anterior thalamic pathology.SIGNIFICANCE STATEMENT At present, we know little about interactions between temporal lobe and diencephalic memory systems. Here, we focused on the subiculum, as the sole hippocampal formation region directly interconnected with the anterior thalamic nuclei. We combined reversible and permanent lesions of the anterior thalamic nuclei, electrophysiological recordings of the subiculum, and behavioral analyses. Our results were striking and clear: following permanent thalamic lesions, the diverse spatial signals normally found in the subiculum (including place cells, grid cells, and head-direction cells) all disappeared. Anterior thalamic lesions had no discernible impact on hippocampal CA1 place fields. Thus, spatial firing activity within the subiculum requires anterior thalamic function, as does successful spatial memory performance. Our findings provide a key missing part of the much bigger puzzle concerning why anterior thalamic damage is so catastrophic for spatial memory in rodents and episodic memory in humans.     

Anterograde and retrograde amnesia in rats with dorsal hippocampal or dorsomedial thalamic lesions

The present research was concerned with anterograde and retrograde memory for a socially transmitted food preference in rats with lesions to the dorsal hippocampus or dorsomedial thalamus, and operated controls. In Expt. 1, food-preference training was administered postoperatively and memory was tested following various delays. Both lesioned groups acquired the preference normally, but rats with hippocampal lesions displayed a rapid rate of forgetting that indicated significant anterograde amnesia. In Expt. 2, the food preference was acquired at different times preoperatively and retrograde memory was tested postoperatively. Both lesioned groups exhibited loss of memory when training immediately preceded surgery, but only rats with hippocampal lesions displayed a temporally-graded retrograde amnesia. The results confirmed the differential effects of hippocampal and thalamic lesions on memory performance. It was suggested that memory loss following thalamic lesions was related to factors associated with original learning, whereas the pattern of hippocampal amnesia reflected disruption at a later stage in the learning process.     

Vascular thalamic amnesia: a reappraisal

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.     

The role of the thalamus in amnesia: a tractography, high-resolution MRI and neuropsychological study

Although it is well established that thalamic lesions may lead to profound amnesia, the precise contribution of thalamic sub-regions to memory remains unclear. In an influential article Aggleton and Brown proposed that recognition memory depends on two processes supported by distinct thalamic and cortical structures. Familiarity is mediated by the mediodorsal (MD) thalamic nucleus and the entorhinal/perirhinal cortex. Recollection is mediated by the anterior thalamic nucleus (AN), the mamillothalamic tract (MTT) and the hippocampus. The authors also suggested that the lateral dorsal nucleus (LD) may contribute to the thalamic/hippocampus system, thereby implying that the LD may play a role in recollection. Given the finding that material specific amnesia can occur following thalamic lesions, we tested an extension of the Aggleton and Brown model. We predicted that patients with bilateral lesions with a bias to the left or right MD or AN/MTT/LD may exhibit impaired familiarity or recollection on verbal or non-verbal memoranda. We report two patients with highly focal thalamic lesions and profound memory impairments affecting verbal and non-verbal memoranda. For the first time, diffusion-weighted imaging was employed to perform tractography of the MTT along with high-resolution anatomical MRI and detailed assessments of verbal and non-verbal memory. Our data support only some aspects of the Aggleton and Brown model. Both patients had left MD nucleus and AN/MTT lesions and performed poorly on familiarity and recall for verbal memoranda, just as predicted by the model. However, both patients' performance for non-verbal memoranda (human faces and topography) is more difficult to reconcile with the model. Patient 1 had damage to the right AN/MTT/LD with sparing of the MD: familiarity should therefore have been preserved but was not. Patient 2 had damage to the right MD with sparing of AN/MTT: recollection should have been preserved but was not. This finding raises the possibility that fractionation of familiarity and recollection to separate thalamic nuclei may not fully capture the role of thalamic sub-regions in memory function.     

Normal memory after damage to medial thalamus

We studied two patients with nonhemorrhagic infarcts of the thalamus and assessed their cognitive functions comprehensively using standardized neuropsychological probes. Neither patient had any discernible memory impairment for verbal or nonverbal material. Analysis of magnetic resonance images with a stereotaxic method revealed that one subject had a right-sided lesion involving about 15% of the dorsomedial nucleus (DM). The other had bilateral lesions that affected about 15% of the left DM and less than 5% of the right DM. The mamillothalamic tract appeared intact in both patients. Considering that medial thalamic lesions commonly cause amnesia in human beings as well as nonhuman primates, there are two possible reasons, alone or in combination, that may explain why these patients failed to have amnesia: the amount of DM damage was less than required to cause amnesia; or the amnesia related to thalamic lesions requires damage to a second structure, such as the mamillothalamic tract or the anterior nucleus.     

Left antero-medial thalamic infarction and symptoms of amnesia, aphasia, and dementia

Three cases of left antero-medial thalamic infarction who showed amnesia, aphasia and dementia were studied comparatively in terms of clinical features and the MRI findings. Case 1 and Case 2, who showed transient amnesia and aphasia respectively, had a single lesion in the left antero-medial thalamus. Case 1 had a lesion in a more ventral part than Case 2, suggesting that Case 1 had a lesion of the bundles into the anterior and dorsomedial thalamic nuclei while Case 2 had a lesion of the ventrolateral thalamic nucleus. On the other hand, Case 3 who showed persistent dementia had multiple lesions in addition to the left antero-medial thalamic infarction. A review of the previous reports and investigations of the present cases suggest that a single ischemic lesion in the left antero-medial thalamus will cause amnesia and/or aphasic symptom while in cases with other multiple lesions it may cause persistent dementia.     

An atypical neuropsychological profile of a Korsakoff syndrome patient throughout the follow-up

The basis of amnesia in alcoholic Wernicke-Korsakoff syndrome (WKS) has been generally associated with diencephalic lesions and more specifically with lesions of the anterior thalamic nuclei. These brain structures are considered to be involved in encoding/consolidation processes of episodic memory. However, frontal lobe damage responsible for executive function deficits has also been documented. The present report details the nature and extent of amnesia in an alcoholic patients with WKS and which appears to be mainly due to frontal lobe (executive) deficits.     

Dissociable memory effects after medial thalamus lesions in the rat

Variable neuropathology in cases of diencephalic amnesia has led to uncertainty in identifying key thalamic nuclei and their potential role in learning and memory. Based on the principal neural connections of the medial thalamus, the current study tested the hypothesis that different aggregates of thalamic nuclei contribute to separate memory systems. Lesions of the anterior thalamic aggregate (AT), which comprises the anterodorsal, anteromedial and anteroventral nuclei produced substantial deficits in both working and reference spatial memory in a radial arm maze task in rats, supporting the view that the AT is an integral part of a hippocampal memory system. Lesions to the lateral thalamic aggregate (LT), which comprises the intralaminar nuclei (centrolateral, paracentral and rostral central medial nuclei) and lateral mediodorsal thalamic nuclei (lateral and paralamellar nuclei) produced a mild working memory impairment only, while lesions to the posteromedial thalamic aggregate (MT), which comprises the central and medial mediodorsal thalamic nuclei and the intermediodorsal nucleus had no effect on radial arm maze performance. In contrast, only MT lesions impaired learning associated with memory for reward value, consistent with the idea that the MT contributes to an amygdala memory system. Compared with chance discrimination, the control and AT groups, but not MT or LT groups, showed evidence for temporal order memory for two recently presented objects; all groups showed intact object recognition for novel vs. familiar objects. These new dissociations show that different medial thalamic aggregates participate in multiple memory systems and reinforce the idea that memory deficits in diencephalic amnesics may vary as a function of the relative involvement of different thalamic regions.     

Right medial thalamic lesion causes isolated retrograde amnesia.

Pervasive retrograde amnesia without anterograde memory impairment has rarely been described as a consequence of circumscribed brain damage. We report this phenomenon in a 33 yr-old, right-handed man (JG) in association with the extension in the right thalamus of a previously small, bilateral thalamic lesion. JG presented with a dense amnesia for autobiographical material more than a few years old, with some sparing of recent memories. Furthermore, he was completely unable to recognise famous people or world events. Many other aspects of semantic knowledge were intact and there was no evidence of general intellectual impairment, executive dysfunction or loss of visual imagery. Magnetic resonance imaging revealed an acute lesion in the right thalamus and two small, symmetrical, bilateral non-acute thalamic lesions. Follow-up neuropsychological assessment indicated a stable pattern of impaired retrograde and spared anterograde memory over 18 months and psychiatric assessments yielded no evidence of confabulation, malingering or other symptoms to suggest psychogenic amnesia. JG's profile indicates that the division of declarative memory into just two categories - episodic and semantic - is inadequate. Rather, his case adds to the growing body evidence to suggest that world knowledge pertaining to people and events is stored or accessed similarly to autobiographical information and differently from other types of more general factual knowledge. We hypothesize that the right mediodorsal thalamic nucleus and immediately surrounding regions comprise the central processing mechanism referred to by McClelland (Revue Neurologique, 150 (1994) 570) and Markowitsch (Brain Research Review, 21 (1995) 117) as responsible for inducing and co-ordinating the recall of these sorts of cortically stored memory engrams.     

Autobiogutobiographical amnesia and cognltive disorder resulgting from bilateral severe thalamic infarction Two cases reports

Objective To report two cases of patients with bilateral severe thalamic infarction.which showed autobiographical amnesia and cognitive disorders and to shed light on the mechanisms underlying thc retrograde amenesia. Method The two cases were studied clinically, CT and MRI were performed also, Language and neuropsychological tests were evaluated. Results Two patients with a chronic amnesia and cogntive disorders resulting from bilateral paramedian thalamic infarction showed a pattern of retrograde amnesia personally relevent autobiographical memory were prefoundly impaired .Whereas about the famous people and public events were relatively impaired. The patients almost had no thalamic aphasia.The events the one described showed spontaneously confabulated. Conclusion We think a probable explanation that the disorders at the thematic retrieval fiomwork ievel of memory and the information reconstruction due to a disconnetion of frontal and medial temperal memory systems.     

Implicit and explicit memory after focal thalamic lesions.

BACKGROUND: Lesions of the thalamus interfere with cognitive functions mainly in the area of declarative learning and memory. Little is known about the role the thalamus plays in implicit learning. OBJECTIVE: To study explicit and implicit learning and memory in subjects with thalamic lesions and to analyze the influence of lesion characteristics on cognitive performance. METHODS: The authors studied the performance of 15 subjects with focal thalamic infarction or hemorrhage on a comprehensive neuropsychological test battery focusing on tests of explicit memory and learning of a nondeclarative motor skill. Subjects with thalamic lesions were compared to 15 healthy matched control subjects and to a clinical control group of 22 subjects who had sustained basal ganglia lesions. RESULTS: Subjects with thalamic lesions showed well-preserved intellectual and executive functions but demonstrated deficits on measures of attention and psychomotor speed, explicit memory, and implicit visuomotor sequence learning. Lesion size in the thalamus was clearly related to subjects' long-term explicit memory performance. However, few of the neuropsychological deficits found seemed specific to the long-term neuropsychological outcome of focal thalamic infarctions. Subjects with lesions in the basal ganglia demonstrated similar deficits. CONCLUSIONS: Focal subcortical lesions in the thalamus and the basal ganglia lead to a similar profile of neuropsychological deficits. Lesions in the thalamus not only affect declarative memory but also interfere with nondeclarative motor skill learning.     

Hippocampal Amnesia

This article reviews 147 cases of amnesia following damage including the hippocampus or fornix as reported in 179 publications. The aetiology, mnestic abilities and reference(s) are tabulated for each case. Consistent findings across cases include the association of bilateral hippocampal damage with a deficit in anterograde episodic memory combined with spared procedural and working memory. The limited nature of retrograde amnesia following lesions to the fornix is also noted. Less consistent and thus more controversial findings, include effects of lesion size or laterality, deficits in semantic memory or familiarity-based recognition and the extent of retrograde amnesia. The evidence concerning these issues is reviewed across cases.     

Selective anterograde amnesia with thalamus and hippocampal lesions in neuro-Behcet's disease

Anterograde amnesia and minimal retrograde amnesia with thalamic and hippocampal lesions in neuro-Behcet's disease is rare. A 50-year-old man presented with forgetfulness and severe memory disturbance after suffering multiple oral and genital aphthous ulcers with erythema nodosum. A neurological examination and a neuropsychological assessment revealed prominent anterograde memory impairment without focal neurological deficits. On brain MRI there were high signal intensity lesions involving right anterior thalamus, left posterior basal ganglia, and left hippocampus. This is a quite selective anterogrde memory deficit in a case of neuro-Behcet's disease caused by parenchymal lesions in the thalamus and hippocampus.     

The hippocampus and thalamus: their roles in short- and long-term memory and the effects of interference

Rats with dorsal hippocampal, dorsomedial thalamic, and operated control lesions were administered a delayed alternation (DA) task in which recall was assessed over intervals ranging between 0 and 80 s, and a passive avoidance (PA) task, involving training-test delays of between 1 h and 21 days. On both tasks, hippocampal groups performed normally at relatively short intervals, but showed significant memory loss at longer intervals. Thalamic groups were generally impaired on the DA task, but performed as well as operated control groups at all intervals in the PA task. The data also indicated an exaggerated susceptibility to interference in the hippocampal groups and a loss of episodic and reference memory following hippocampal or thalamic lesions. Similarities between the performance of rats with hippocampal or thalamic lesions and comparably brain-damaged human amnesics were noted. In line with current hypotheses, it was concluded that memory loss following thalamic damage is related to a deficit in the early stages of new learning, whereas hippocampal amnesia results from impairment at a later, integrative stage in which long-term memories are formed and durably stored.     

Thalamic aphasia

Summary Four patients with aphasia due to small circumscribed thalamic lesions are presented. A review of the literature on thalamic aphasia revealed 16 similar cases. While the general consensus that only left-sided thalamic lesions are associated with aphasia is confirmed, analysis of the sites of the thalamic infarctions and the dysphasia elements did not reveal an unequivocal correlation. The explanation of this finding is that (a) disruption of any circuit, whether taking place in the connections or in the nuclei, leads to dysfunction and (b) thalamofrontal connections are not topographically arranged according to the thalamic nuclei, but show a frontal rostrocaudal/thalamic mediolateral interrelationship irrespective of thalamic nuclear masses.     

Mediodorsal Thalamic Lesions Impair Long-Term Visual Associative Memory in Macaques

Six cynomolgus monkeys (Macaca fascicularis) were trained to associate visual stimuli with the delivery of various amounts of food reward. The animals had to choose correctly between pairs of stimuli drawn from a population of 16. Four of these stimuli were associated with 0 reward pellets, four with 1 pellet, four with 2 pellets and four with 4 pellets. Mediodorsal thalamic lesions including the medial part of the mediodorsal nucleus, similar to those which are frequently seen in Korsakoff amnesia, produced a severe impairment in this task. The impairment was seen both in memory for the quantity of reward, as expressed in choices between 1-pellet and 2-pellet stimuli or choices between 2-pellet and 4-pellet stimuli, and also in memory for the qualitative absence or presence of reward, as expressed in choices between 0-pellet and 1-pellet stimuli. The deficit in this task establishes that mediodorsal thalamic lesions in monkeys can impair long-term memory tasks, in addition to their known effects on several short-term memory tasks. The contrast between the present results and those of previous experiments on visual long-term memory in the monkey following mediodorsal thalamic lesions can be related to similar contrasts in studies of lesions in the amygdala, suggesting that the functions of these two structures are related.     

Deficits of memory,executive functioning and attention following infarction in the thalamus; a study of 22 cases with localised lesions

The thalamus plays a crucial role in memory, executive functioning and attention. It remains, however, unclear whether thalamic structures have specific roles in each of these functions. We tested 22 cases of thalamic infarction, proven with MR imaging, using experimental and established neuropsychological tests. We performed a lesion-overlap study in standardised stereotactic space of patients sharing a certain deficit, corrected for the lesion distribution of patients without such deficits and determined the regions of interest using an atlas of the human thalamus. We checked for additional, non-thalamic, damage and for deficient comprehension and perception that would preclude interpretation of the results. Non-thalamic damage such as white matter lesions, hippocampal atrophy, sulcal widening and infarctions occur significantly more often in patients aged over 60. The patients with additional damage overlapped to a major degree with those who showed loss of orientation, or lack of comprehension of the test requirements. In the 10 patients judged 'clean', we observed a deficit of episodic long-term memory with relative sparing of intellectual capacities and short-term memory when the mammillo-thalamic tract was damaged. Lesions including the medial dorsal nucleus, midline nuclei and/or intralaminar nuclei accompany executive dysfunctioning. Reduced simple processing speed and attention are associated with age, but not with a particular structure in the thalamus. Complex attention deficits follow damage to the intralaminar nuclei.We conclude that the analysis of structure-function relationships must take into account extra-structure damage which may explain cognitive deficits. Separate thalamic structures are involved in memory, executive functioning and attention.     

Learning impairments in monkeys with combined but not separate excitotoxic lesions of the anterior and mediodorsal thalamic nuclei

Clinical studies in humans and experiments in macaques suggest that damage to the anterior and the mediodorsal thalamus can induce a moderate amnesia, but a more dense impairment may result from substantial damage within the temporal lobes or their subcortical connections. Lesions of the anterior thalamus in macaques produce impairments which resemble those seen after lesions of the fornix–mamillary pathway, which carries projections from the hippocampus to the anterior thalamus, while lesions of the mediodorsal thalamus, which receives inputs from frontal and temporal cortex, produce moderate impairments on a wider range of memory tasks. In the present study, we have made bilateral excitotoxic lesions of either the anterior or the mediodorsal thalamus, or both, in marmoset monkeys. Monkeys with lesions of both thalamic nuclei were severely impaired on retention and new learning of examples of the visuospatial conditional task, a task which is specifically impaired by lesions of the fornix or hippocampus. They were not impaired on performance of a visuovisual conditional task on which monkeys with hippocampal lesions are impaired, nor were they impaired on any visual discrimination task, including the concurrent discrimination task on which monkeys with temporal neocortical ablations are impaired. Monkeys with separate lesions of either the anterior or the mediodorsal thalamus were not impaired on any of these tasks. These results suggest that the mediodorsal thalamus and the anterior thalamus are both involved in processing the output of the hippocampal–fornix–thalamic circuit. Dense amnesia may result from damage to circuits additional to the temporal lobe efferents to either the anterior or the mediodorsal nuclei.