Recall and recognition memory in amnesia: patients with hippocampal, medial temporal, temporal lobe or frontal pathology

The relationship between recall and recognition memory impairments was examined in memory-disordered patients with either hippocampal, medial temporal, more widespread temporal lobe or frontal pathology. The Hirst [Hirst, W., Johnson, M. K., Phelps, E. A., & Volpe, B. T. (1988). More on recognition and recall in amnesics. Journal of Experimental Psychology: Learning, Memory, & Cognition, 14, 758-762] technique for titrating exposure times was used to match recognition memory performance as closely as possible before comparing recall memory scores. Data were available from two different control groups given differing exposure times. Each of the patient groups showed poorer recall memory performance than recognition scores, proportionate to the difference seen in healthy participants. When patients' scores were converted to Z-scores, there was no significant difference between mean Z-recall and Z-recognition scores. When plotted on a scatterplot, the majority of the data-points indicating disproportionately low recall memory scores came from healthy controls or patients with pathology extending into the lateral temporal lobes, rather than from patients with pathology confined to the medial temporal lobes. Patients with atrophy extending into the parahippocampal gyrus (H+) performed worse than patients with atrophy confined to the hippocampi (H-); but, when H- patients were given a shorter exposure time (5s) and compared with H+ at a longer exposure (10s), their performance was virtually identical and did not indicate any disproportionate recall memory impairment in the H- group. Parahippocampal volumes on MRI correlated significantly with both recall and recognition memory. The possibility that findings were confounded by inter-stimulus artefacts was examined and rejected. These findings argue against the view that hippocampal amnesia or memory disorders in general are typically characterised by a disproportionate impairment in recall memory. Disproportionate recall memory impairment has been observed in a number of published cases, and the reason for the varying pattern obtained across hippocampal patients requires further examination.     

Role of the medial temporal lobes in relational memory: neuropsychological evidence from a cued recognition paradigm

In this study, we examined the role of the hippocampus in relational memory by comparing item recognition performance in amnesic patients with medial temporal lobe (MTL) damage and their matched controls. Specifically, we investigated the contribution of associative memory to item recognition using a cued recognition paradigm. Control subjects studied cue-target pairs once, whereas amnesic patients studied cue-target pairs six times. Following study, subjects made recognition judgments about targets that were presented either alone (no cue), with the originally presented cue (same cue), or with a cue that had been presented with a different target (recombined cue). Controls had higher recognition scores in the same cue than in the recombined cue condition, indicating that they benefited from the associative information provided by the same cue. By contrast, amnesic patients did not. This was true even for a subgroup of patients whose recognition performance in the no cue condition was matched to that of the controls. These data provide further support for the idea that the hippocampus plays a critical role in relational memory, even when associative information need not be retrieved intentionally.     

Recognition memory for faces and scenes in amnesia: dissociable roles of medial temporal lobe structures

The relative contributions of the hippocampus and the perirhinal cortex to recognition memory are currently the subject of intense debate. Whereas some authors propose that both structures play a similar role in recognition memory, others suggest that the hippocampus might mediate recollective and/or associative aspects of recognition memory, whereas the perirhinal cortex may mediate item memory. Here we investigate an alternative functional demarcation between these structures, following reports of stimulus-specific perceptual deficits in amnesics with medial temporal lobe (MTL) lesions. Using a novel recognition memory test for faces and scenes, participants with broad damage to MTL structures, which included the hippocampus and the perirhinal cortex, were impaired on both face and scene memory. By contrast, participants with damage limited to the hippocampus showed deficits only in memory for scenes. These findings imply that although both the hippocampus and surrounding cortex contribute to recognition memory, their respective roles can be distinguished according to the type of material to be remembered. This interaction between lesion site and stimulus category may explain some of the inconsistencies present in the literature.     

Patients with heart attacks are not valid models for medial temporal lobe amnesia. A neuropsychological and FDG-PET study with consequences for memory research

Equating the condition after cardiac arrest with that of medial temporal damage, and consequently medial temporal lobe amnesia, is questioned on the basis of results from a patient who was studied neuropsychologically as well as with static and dynamic imaging methods (MRI, PET) 6–9 months after a heart attack. The patient manifested severe and persistent anterograde and retrograde amnesia, as well as further cognitive deteriorations. While MRI only indicated non-specific cortical atrophy, PET revealed a severe bilateral affection of the thalamus and of both medial and lateral temporal cortices as well as occipito-parietal hypometabolism. The neuropsychological status indicates that patients with a diagnosis of cardiac arrest may suffer very severe and persistent cognitive deficits; the imaging analyses show that cardiac arrests may lead to quite severe and widespread brain damage which, however, may not be visible with current magnetic resonance imaging technology, but which is clearly apparent from positron emission tomography. These data suggest that patients with a condition after a heart attack may not be valid models for pure hippocampal—or even medial temporal lobe—pathology, as they may suffer much more widespread brain damage.     

Role of monkey hippocampus in recognition of food and nonfood

To investigate the role of the hippocampal formation (HF) in feeding behavior, single neuron activity in the monkey HF was recorded during performance of an operant task that included food/nonfood discrimination, drinking, and active avoidance. Of 837 neurons recorded in the HF, 155 responded to the sight of one or more objects. Of these, 82 responded to the sight of different objects with different response magnitudes, and some of these 82 responded predominantly to food-related (rewarding) objects or nonfood, aversive objects. The magnitude of response of neurons that responded predominantly to food was not necessarily correlated with the order of animal's preference for those kinds of food. For some neurons that responded predominantly to food or nonfood, effects of extinction or reversal learning on the neuronal responses were tested, and most of the neurons tested maintained their original responsiveness even after behavioral extinction or reversal learning was accomplished. The results suggest that these HF neurons may be involved in preservation of past information concerning food or nonfood.     

Saccadic eye movements, even in darkness, generate event-related potentials recorded in medial septum and medial temporal cortex

Saccadic eye movements (saccades) in primates organize the visual information about the environment into a pulsatile course. Recent studies from our laboratory have found substantial single unit activity, of extra-retinal origin, in medial temporal and inferotemporal cortex with each saccade (even in the dark). In the current experiment we studied event-related potentials to spontaneous saccades from electrodes in medial temporal cortex as well as medial septum. Significant event-related potentials were recorded in both regions (again even in the dark). These data suggest that higher-level processing itself may synchronize with saccades.     

Material-specific lateralization of working memory in the medial temporal lobe

Mnemonic deficits in patients with medial temporal lobe (MTL) damage arising from temporal lobe epilepsy (TLE) are traditionally constrained to long-term episodic memory, sparing short-term and working memory (WM). This view of WM as being independent of MTL structures has recently been challenged by a small number of patient and neuroimaging studies, which have focused primarily on visual and visuospatial WM. In the present study we investigated material-specific lateralization of WM in 96 patients with unilateral damage to MTL stemming from TLE (56 left) and 30 control subjects using a pair of matched verbal and visuospatial supraspan tasks. Patients with unilateral TLE were impaired on both verbal and visuospatial WM tasks irrespective of the affected hemisphere. Patients with unilateral right TLE showed an additional deficit for visuospatial WM capacity when contrasted with patients with left TLE, whereas patients with unilateral left TLE showed increased intrusion errors on the verbal task when compared to patients with right TLE. These findings suggest a material-specific lateralization of WM in the MTL.     

Performance in recognition memory is correlated with entorhinal/perirhinal interictal metabolism in temporal lobe epilepsy

In addition to the hippocampus, the entorhinal/perirhinal cortices are often involved in temporal lobe epilepsy (TLE). It has been proposed that these anterior parahippocampal structures play a key role in recognition memory. We studied the voxel-based PET correlation between number of correctly recognized targets in a new recognition memory paradigm and interictal cerebral metabolic rate for glucose, in 15 patients with TLE with hippocampal sclerosis. In comparison to healthy subjects, patients had decreased recognition of targets (P<0.001) and ipsilateral hypometabolism (relative to side of hippocampal sclerosis) of the hippocampus, entorhinal/perirhinal cortices, medial temporal pole, and middle temporal gyrus (P<0.05, corrected by false discovery rate method). Performance correlated with interictal metabolism of ipsilateral entorhinal/perirhinal cortices (P<0.005, Spearman's rank test), but this relationship was not significant in the hippocampus itself (P>0.18, Spearman's rank test). These findings highlight the preferential involvement of entorhinal/perirhinal cortices in recognition memory in patients with TLE, and suggest that recognition memory paradigms may be useful in assessing anterior parahippocampal functional status in TLE.     

The contribution of familiarity to associative memory in amnesia

In Experiment 1, using the remember/know paradigm with control participants, we compared the contribution of recollection and familiarity to associative recognition for compound stimuli and for unrelated word pairs. It was demonstrated that familiarity makes a greater contribution to associative recognition of compound stimuli than to associative recognition of unrelated word pairs. In Experiment 2, we examined associative recognition memory in medial temporal lobe amnesics, diencephalic amnesics, and control participants for the stimuli employed in Experiment 1. Whereas associative recognition for compounds and unrelated words was nearly identical in control participants, associative recognition was higher for compounds than for unrelated word pairs in amnesic patients. This pattern was observed in the medial temporal amnesic group as well as in the diencephalic amnesic group. These results suggest that associative recognition in amnesia is enhanced to the extent that performance can be supported by study-induced familiarity for the studied pair.     

颞叶癫痫大鼠海马CA1区突触可塑性与空间记忆能力关系的研究

目的探讨颞叶癫痫大鼠海马CA1区突触超微结构与空间记忆能力改变的关系。方法以海人酸杏仁核微量注射建立经典的雄性Wistar大鼠颞叶癫痫化学点燃模型,分别于点燃后11d、17d、21d测定大鼠的空间记忆能力,并观察第21d海马CA1区神经毡突触超微结构变化。结果颞叶癫痫大鼠空间记忆能力减低,同时伴有海马CA1区神经毡内突触数密度降低(P<0．05),突触活性区膜面积缩小(P<0．05),突触界面曲率降低(P< 0．05),比表面减小(P<0．05),突触小泡数密度降低(P<0．05)。结论颞叶癫痫大鼠海马CA1区神经毡内突触损害和活力可能是导致其空间记忆能力下降的重要机制。     

Resection extent versus postoperative outcomes of seizure and memory in mesial temporal lobe epilepsy

OBJECTIVES: To investigate the effects of the resection of hippocampus and temporal neocortex on postsurgical seizure and memory outcomes in mesial temporal lobe epilepsy (mTLE) patients. METHODS: Sixty-eight mTLE patients underwent pre- and postsurgical brain magnetic resonance imaging (MRI). The patients were divided into seizure-free group (SF, N=54) and non-seizure-free group (NSF, N=14). The resection length of hippocampus was determined by the difference between presurgical and postsurgical hippocampus lengths in MRIs. The lengths of resected temporal gyri were measured on three-dimensional MRI reconstruction. Among SF group, 37 patients performed pre- and postsurgical neuropsychological tests. The postsurgical memory decline (PMD) was calculated by subtracting postsurgical memory score from presurgical one in verbal and visual memory tests. RESULTS: The resection length of hippocampus in SF was significantly longer than in NSF (32.7 +/- 7.7 mm versus 25.1 +/- 7.3 mm, t-test, p=0.002), regardless of intersubject difference in the extent of hippocampal sclerosis (logistic regression, p=0.003) while the resection lengths of the lateral temporal gyri were not different between SF and NSF. Overall postsurgical change of verbal or visual memory was not significant. However, regression analysis showed a significant correlation between the resection length of inferior or basal temporal gyrus and verbal PMD (p<0.001) in left TLE patients with seizure-free outcome. CONCLUSION: More resection of hippocampus may predict a better postsurgical seizure-free outcome. The larger resection of inferior or basal temporal gyrus seems to be related to a postsurgical verbal memory decline in left TLE patients.     

Automatic temporal lobe atrophy assessment in prodromal AD: Data from the DESCRIPA study

BackgroundIn the framework of the clinical validation of research tools, this investigation presents a validation study of an automatic medial temporal lobe atrophy measure that is applied to a naturalistic population sampled from memory clinic patients across Europe.MethodsThe procedure was developed on 1.5-T magnetic resonance images from the Alzheimer's Disease Neuroimaging Initiative database, and it was validated on an independent data set coming from the DESCRIPA study. All images underwent an automatic processing procedure to assess tissue atrophy that was targeted at the hippocampal region. For each subject, the procedure returns a classification index. Once provided with the clinical assessment at baseline and follow-up, subjects were grouped into cohorts to assess classification performance. Each cohort was divided into converters (co) and nonconverters (nc) depending on the clinical outcome at follow-up visit.ResultsWe found the area under the receiver operating characteristic curve (AUC) was 0.81 for all co versus nc subjects, and AUC was 0.90 for subjective memory complaint (SMC_nc) versus all co subjects. Furthermore, when training on mild cognitive impairment (MCI-nc/MCI-co), the classification performance generally exceeds that found when training on controls versus Alzheimer's disease (CTRL/AD).ConclusionsAutomatic magnetic resonance imaging analysis may assist clinical classification of subjects in a memory clinic setting even when images are not specifically acquired for automatic analysis.     

The renin-angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis

Purpose: As reported by several authors, angiotensin II (AngII) is a proinflammatory molecule that stimulates the release of inflammatory cytokines and activates nuclear factor κB (NFκB), being also associated with the increase of cellular oxidative stress. Its production depends on the activity of the angiotensin converting enzyme (ACE) that hydrolyzes the inactive precursor angiotensin I (AngI) into AngII. It has been suggested that AngII underlies the physiopathological mechanisms of several brain disorders such as stroke, bipolar disorder, schizophrenia, and disease. The aim of the present work was to localize and quantify AngII AT1 and AT2 receptors in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis (MTS) submitted to corticoamygdalohippocampectomy for seizure control.
Method: Immunohistochemistry, Western blot, and real-time PCR techniques were employed to analyze the expression of these receptors.
Results: The results showed an upregulation of AngII AT1 receptor as well as its messenger ribonucleic acid (mRNA) expression in the cortex and hippocampus of patients with MTS. In addition, an increased immunoexpression of AngII AT2 receptors was found only in the hippocampus of these patients with no changes in its mRNA levels.
Discussion: These data show, for the first time, changes in components of renin-angiotensin system (RAS) that could be implicated in the physiopathology of MTS.     

Dopamine D1 receptor activity modulates object recognition memory consolidation in the perirhinal cortex but not in the hippocampus

It has been proposed that distributed neuronal networks in the medial temporal lobe process different characteristics of a recognition event; the hippocampus has been associated with contextual recollection while the perirhinal cortex has been linked with familiarity. Here we show that D1 dopamine receptor activity in these two structures participates differentially in object recognition memory consolidation. The D1 receptor antagonist SCH23390 was infused bilaterally 15 min before a 5 min sample phase in either rats' perirhinal cortex or dorsal hippocampus, and they were tested 90 min for short‐term memory or 24 h later for long‐term memory. SCH23390 impaired long‐term memory when infused in the perirhinal cortex but not when infused in the hippocampus. Conversely, when the D1 receptor agonist SKF38393 was infused 10 min before a 3 min sample phase in the perirhinal cortex, long‐term memory was enhanced, however, this was not observed when the D1 agonist was infused in the hippocampus. Short‐term memory was spared when SCH23390 or SKF38393 were infused in the perirhinal cortex or the dorsal hippocampus suggesting that acquisition was unaffected. These results suggest that dopaminergic transmission in these medial temporal lobe structures have a differential involvement in object recognition memory consolidation. © 2013 Wiley Periodicals, Inc.     

The relationship between quantitative T2 relaxometry and memory in nonlesional temporal lobe epilepsy

PURPOSE: We investigated the relationship between preoperative quantitative magnetic resonance imaging (MRI) T2 relaxometry and volumetry of the hippocampi and pre- and postoperative verbal memory in temporal lobectomy patients who had nonlesional temporal lobe epilepsy. METHODS: Pre- and postoperative memory data based on the Logical Memory (LM) subtest of the Wechsler Memory Scale-Revised (WMS-R) and the 30-min delayed recall trial of the Rey Auditory Verbal Learning Test (AVLT) were obtained from 26 left and 15 right temporal lobectomy patients. Coronal MRI T2 maps were generated for these 41 temporal lobectomy patients as well as 61 control patients. Hippocampal T2 relaxation times and hippocampal volumes, converted to z scores using control group data, were correlated with neuropsychological performance in the patients. RESULTS: In left temporal lobe-onset patients, high T2 in the left hippocampal body predicted higher LM performance after surgery. Asymmetrically high T2 in the left hippocampal body (i.e., the right-minus-left difference), compared with the right hippocampal body, also predicted higher LM performance after surgery. In right temporal lobe-onset patients, high T2 in the left hippocampal body predicted relatively lower AVLT performance after surgery. Multiple regression analysis in left temporal-onset patients revealed that high T2 in the left hippocampal body together with higher preoperative LM performance predict higher postoperative LM performance. CONCLUSIONS: Our findings suggest that elevated (i.e., abnormal) hippocampal T2 signal is associated with memory ability (or hippocampal functional capacity) independent of MRI-determined hippocampal atrophy. Therefore, our findings support the use of quantitative T2 relaxometry as an independent predictor of verbal memory outcome in both left and right TLE patients who are candidates for temporal lobectomy.     

Understanding medial temporal activation in memory tasks: evidence from fMRI of encoding and recognition in a case of transient global amnesia

We used fMRI to examine the activation patterns of patient AE during encoding and recognition of visual scenes during an episode of transient global amnesia (TGA) and 3 months later. Controls (n = 5) showed bilateral (R > L) activation in parahippocampal and fusiform gyri during encoding and right-sided activation in the same regions associated with recognition of previously viewed scenes. AE showed a similar pattern at follow-up. During acute TGA, when performance was profoundly impaired, AE showed no medial temporal activation associated with encoding of new scenes or recognition of old scenes. In both contrasts, the percent signal change in relevant medial temporal regions was more than three standard deviations below the control sample mean. She did, however, show striking bilateral hippocampal activation for recognition attempts (old + new scenes > baseline) even though retrieval was unsuccessful (55% recognition accuracy). This finding was unique to AE on this occasion. This is the first study to document normalization of both encoding and recognition activation patterns in TGA. Furthermore, the strong hippocampal activation during unsuccessful retrieval highlights important issues in interpreting memory-related activations, particularly in dysfunctional systems.