The decay of memory between delayed and long-term recall in patients with temporal lobe epilepsy

OBJECTIVES: Impairment of long-term recall may worsen everyday functioning of patients with epilepsy even if the standard short-term or delayed recall tests do not show significant abnormalities. We evaluated prospectively the decay of memory between delayed and long-term recall in patients with temporal lobe epilepsy (TLE) and controls with the aim of identifying the determinants of long-term memory impairment. METHODS: Seventy patients with TLE and 59 controls underwent neuropsychological assessment of verbal and nonverbal memory, attention, and executive functions at visit 1. Long-term verbal and nonverbal memory was tested with the same word list, verbal logical story, and Rey-Osterrieth complex figure test 4 weeks later at visit 2. The decay in memory was estimated as information recalled at visit 2 as a percentage of the delayed recall at visit 1. RESULTS: Frequent seizures (> or = 4 per month) during the study period were related to poor long-term recall, even for those patients who did relatively well on delayed recall tests. On all long-term memory tests, patients with complex partial and/or secondary generalized seizures did significantly worse than patients with simple partial seizures. The presence of interictal generalized or focal temporal epileptiform activity was associated with more accelerated forgetting of the word list and complex figure. Multiple regression analysis confirmed that number of complex partial seizures, age of patient, and abnormal interictal EEG are significant predictors of accelerated forgetting. CONCLUSIONS: Uncontrolled seizures, especially with ictal impairment of consciousness, can be a significant factor in the accelerated decay of memory, although subclinical interictal epileptiform EEG activity may also be relevant.     

Long-term accelerated forgetting of verbal and non-verbal information in temporal lobe epilepsy

IntroductionWe investigated whether pre-surgical patients with temporal lobe epilepsy (TLE) forget verbal and non-verbal material faster than healthy controls over retention intervals of an hour and 6 weeks, and whether any observed memory loss was associated with structural changes to the hippocampus and/or seizure frequency.MethodsA mixed factorial design compared the performance of 27 patients with TLE and 22 healthy control participants, matched for IQ, age and gender, on tests of story recall and complex figure recall at three delays: immediate, 1 h and 6 weeks. Performance of the patient and control groups was matched at the immediate delay, which enabled comparisons of forgetting rate over the longer delays.ResultsWe found that TLE can affect the acquisition and retention of new memories over a relatively short delay of 1 h. This deficit was associated with structural hippocampal abnormality, with a material-specific effect that was particularly evident for the verbal task. We also found evidence of accelerated long-term forgetting in both patient groups, for the verbal and non-verbal tasks. It was demonstrated most strongly on the verbal task by the patients with right lateralized hippocampal sclerosis whose verbal recall was normal at the 1-h delay. Accelerated long-term forgetting was not associated with hippocampal pathology, but was associated with the frequency of epileptic seizures.DiscussionThe findings from the verbal task in particular provide evidence consistent with an extended period of memory consolidation that can be disrupted by both left and right TLE. The material-specific effects at the 1-h delay only, suggest that the initial consolidation of verbal and non-verbal, information depends on the integrity of the left and right hippocampus, respectively.     

Reorganization of verbal and nonverbal memory in temporal lobe epilepsy due to unilateral hippocampal sclerosis

PURPOSE: Patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) often suffer from material-specific memory impairments. The purpose of this study was to use functional magnetic resonance imaging (fMRI) to study the organization of specific memory functions in these patients. METHODS: We report 14 patients with unilateral TLE and HS, and 10 controls, performing an fMRI memory paradigm of word, picture, and face encoding. RESULTS: Compared with controls, patients with left TLE demonstrated less left MTL and greater right MTL activation and patients with right TLE demonstrated less right MTL and greater left MTL activation. Correlations between fMRI activation and memory performance revealed greater activation in the damaged left hippocampus to be correlated with better verbal memory performance in left TLE patients and greater right hippocampal activation to be correlated with better nonverbal memory in right TLE patients. Conversely, greater fMRI activation in the contralateral hippocampus correlated with worse memory performance. CONCLUSIONS: Our findings suggest that memory function in unilateral TLE is better when it is sustained by activation within the damaged hippocampus and that reorganization to the undamaged MTL is an inefficient process, incapable of preserving memory function.     

Accelerated long‐term forgetting in children with idiopathic generalized epilepsy

Purpose: The rapid forgetting of information over long (but not short) delays (accelerated long‐term forgetting [ALF]) has been associated with temporal lobe epilepsy but not idiopathic generalized epilepsy (IGE). Long‐term memory formation (consolidation) is thought to demand an interaction between medial temporal and neocortical networks, which could be disrupted by epilepsy/seizures themselves. The present study investigates whether ALF is present in children with IGE and whether it relates to epilepsy severity. Methods: Sixty‐one children (20 with IGE and 41 healthy controls [HC]) of comparable age, sex, and parental socioeconomic status completed neuropsychological tests, including a measure of verbal learning and recall after, short (30‐min) and long (7‐day) delays, and recognition. Epilepsy severity was rated by treating neurologists. Key Findings: A two‐way repeated measures analysis of covariance (ANCOVA) found a significant Group x Delay interaction; the children with IGE recalled (and recognized) significantly fewer words after a long, but not short (2‐ and 30‐min) delay relative to the HC children. Moreover, greater epilepsy severity was associated with poorer recognition. Significance: This study demonstrates, to our knowledge for the first time, that children with IGE present with ALF, which is related to epilepsy severity. These findings support the notion that epilepsy/seizures themselves may disrupt long‐term memory consolidation, which interferes with day‐to‐day functioning of children with IGE.     

Bilateral hippocampal atrophy: consequences to verbal memory following temporal lobectomy

BACKGROUND: Bilateral hippocampal damage is a risk factor for memory decline after anterior temporal lobectomy (ATL). OBJECTIVE: To investigate verbal memory outcome in patients with temporal lobe epilepsy (TLE) with either unilateral or bilateral hippocampal atrophy as measured by MRI. METHODS: The authors selected 60 patients with TLE who had undergone ATL (left = 31, right = 29). They determined normalized MRI hippocampal volumes by cursor tracing 1.5-mm slices from three-dimensional MRI acquisition. Hippocampal volumes were defined as atrophic if the volumes were below 2 SD for control subjects. Bilateral hippocampal atrophy was present in 10 patients with left TLE and 11 patients with right TLE. The authors assessed acquisition, retrieval, and recognition components of verbal memory both before and after ATL. RESULTS: Groups did not differ across age, education, intelligence, age at seizure onset, or seizure duration. Seizure-free rates after ATL were 70% or higher for all groups. Before surgery, patients with left TLE displayed worse verbal acquisition performance compared with patients with right TLE. Patients with left TLE with bilateral hippocampal volume loss displayed the lowest performance across all three memory components. After surgery, both groups of patients with left TLE exhibited worse verbal memory outcome compared with patients with right TLE. Bilateral hippocampal atrophy did not worsen outcome in the patients with right TLE. A higher proportion of patients with left TLE with bilateral hippocampal atrophy experienced memory decline compared with the other TLE groups. CONCLUSION: Bilateral hippocampal atrophy in the presence of left TLE is associated with worse verbal memory before and after ATL compared with patients with unilateral hippocampal volume loss or right TLE with bilateral hippocampal volume loss.     

Accelerated long-term forgetting after amygdalohippocampectomy in temporal lobe epilepsy

Aim of the studyTemporal lobe epilepsy (TLE) has been associated with the phenomenon of accelerated long-term forgetting (ALF). In this study, we aimed to demonstrate the effect of surgery on the ALF phenomena thus contributing to potential explanation of the causal mechanism.Materials and methodsWe evaluated 51 patients with TLE related to hippocampal sclerosis who had amygdalohippocampectomy and had remained seizure-free after surgery. A control group consisted of 24 healthy individuals. All were given a verbal learning test assessing recall after 30 min, 1 week and 6 weeks.ResultsIn our study, the Left-TLE (L-TLE) group showed a statistically significant reduction in the performance at all assessment intervals from 30 min to 1 week compared to the Right-TLE and control groups regarding verbal learning memory test (VLMT) as well as for logical memory. The forgetting rates in the VLMT from 30 min to 1 week were not statistically significantly different between all 3 groups. The logical memory test results equally showed no statistically significant difference in the forgetting rates for the 3 groups between 30 min and 1 week.Conclusions and clinical implicationsThese results may support ongoing debates assuming the initial low performance in the memory of L-TLE patients to be directly related with left hippocampal-temporal tissue loss irrespective of epileptic activity. The discovery of the ALF phenomenon explains that standard memory tests are unable to detect memory loss in some patients who are experiencing a significant level of problems with forgetfulness in their daily lives.     

WMS-III Logical Memory performance after a two-week delay in temporal lobe epilepsy and control groups

Conventional memory assessment may fail to identify memory dysfunction that is characterized by intact recall for a relatively brief period but rapid forgetting thereafter. This study assessed immediate memory and retention after 30-minute and two-week delays in a control group (n = 25) and a group of individuals with temporal lobe epilepsy (TLE, n = 25). For raw free recall, thematic unit, and recognition memory scores from the Wechsler Memory Scale-3rd ed. (WMS-III) Logical Memory (LM) subtest, there were no group x trial interactions and the TLE group performed significantly worse than the controls on all trials. At the individual level, none of the patients (0%) demonstrated isolated free recall impairment at the two-week delay when raw scores were analyzed, and one patient (4%) but also five controls (20%) did so when percent retention scores were examined. In summary, TLE patients did not demonstrate disproportionate forgetting over two weeks on a widely used story memory test.     

Accelerated long-term forgetting in temporal lobe but not idiopathic generalised epilepsy

Temporal lobe epilepsy (TLE) has been associated with the phenomenon of accelerated long-term forgetting (ALF), in which memories are retained normally over short delays but are then lost at an accelerated rate over days or weeks. The causes of ALF, and whether it represents a consolidation deficit distinct from the one associated with forgetting over short delays, remain unclear. In addition, methodological issues have made results of some previous studies difficult to interpret. This study used improved methodology to investigate the role of seizure activity in ALF. Forgetting was assessed in participants with TLE (who have involvement of temporal lobe structures) and idiopathic generalised epilepsy (IGE; in which seizures occur in the absence of identified structural pathology in the temporal lobes). Learning of novel stimuli was matched between patients with TLE, patients with IGE and healthy controls matched for age and IQ. Results indicated that the TLE group showed accelerated forgetting between 30-min and three-weeks, but not between 40-s and 30-min. In contrast, rates of forgetting did not differ between patients with IGE and controls. We conclude that (1) ALF can be demonstrated in TLE in the absence of methodological confounds; (2) ALF is unlikely to be related to the experience of epilepsy that does not involve the temporal lobes; (3) neither seizures during the three-week delay nor polytherapy was associated with ALF.     

Accelerated long-term forgetting in temporal lobe epilepsy: Evidence of improvement after left temporal pole lobectomy

Accelerated long term forgetting (ALF) is a characteristic cognitive aspect in patients affected by temporal lobe epilepsy that is probably due to an impairment of memory consolidation and retrieval caused by epileptic activity in hippocampal and parahippocampal regions. We describe a case of a patient with TLE who showed improvement in ALF and in remote memory impairment after an anterior left temporal pole lobectomy including the uncus and amygdala. Our findings confirm that impairment of hippocampal functioning leads to pathological ALF, whereas restoration of hippocampal functioning brings ALF to a level comparable to that of controls.     

Accelerated long-term forgetting in temporal lobe epilepsy: evidence of improvement after left temporal pole lobectomy

Accelerated long term forgetting (ALF) is a characteristic cognitive aspect in patients affected by temporal lobe epilepsy that is probably due to an impairment of memory consolidation and retrieval caused by epileptic activity in hippocampal and parahippocampal regions. We describe a case of a patient with TLE who showed improvement in ALF and in remote memory impairment after an anterior left temporal pole lobectomy including the uncus and amygdala. Our findings confirm that impairment of hippocampal functioning leads to pathological ALF, whereas restoration of hippocampal functioning brings ALF to a level comparable to that of controls.     

Episodic memory in patients with focal frontal lobe lesions

Episodic memory was evaluated in patients with unilateral, frontal lobe damage and matched controls using a list- method directed forgetting paradigm. Directed forgetting instructions (forget vs. remember the word), encoding instructions (learn vs. judge the word) and test format (recall vs. recognition) were manipulated in order to explore how variations in encoding and retrieval affect verbal memory. Controls demonstrated a normal directed forgetting effect in recall and less directed forgetting in recognition. Patients with left frontal (LF) damage did not show directed forgetting in either recall or recognition and patients with right frontal (RF) damage showed directed forgetting in recall, but not in recognition. Furthermore, the LF group recalled significantly more of the judge than learn words, suggesting that this group's performance improves by providing them with an encoding strategy. Conversely, the RF group's performance did not depend on encoding instructions and their recognition memory was impaired relative to the other two groups when they were instructed to judge the words. Our results suggest that (a) patients with LF damage show deficits in the rehearsal of to-be-remembered information, (b) whereas patients with RF damage show impairments in recognition memory. Furthermore, both patient groups show a lack of directed forgetting when familiarity-based processes guide performance.     

Verbal and nonverbal memory functioning in posttraumatic stress disorder (PTSD)

Although there is evidence for memory impairment in posttraumatic stress disorder (PTSD), it remains unclear whether memory impairment is confined to verbal material or whether memory for nonverbal material is also affected. We examined verbal and nonverbal memory for free recall and recognition in 40 patients with PTSD and 40 healthy controls. Analyses showed that patients with PTSD displayed attenuated memory performance for both short- and long-term recall, which was not further moderated by type of material. The influence of attention, verbal intelligence, and depression was investigated. Our findings suggest that both verbal and nonverbal memory are compromised in PTSD.     

Delayed episodic memory recall after one week is associated with executive functions and divided attention in pediatric epilepsy patients

AimRecent studies suggest that although children with epilepsy may show normal learning and memory performance, accelerated long-term forgetting (ALF) may become evident over time. Our study examined associations between delayed episodic memory performance (recall 1-week after learning) and executive functions.MethodA consecutive sample of children with a diagnosis of idiopathic epilepsy with focal or generalized seizures, without morphologic or metabolic abnormalities (n = 20, mean age: 11.70 years) was compared to an IQ-matched healthy control group (n = 20, mean age: 11.55 years). We also assessed parents’ and children’s rating of forgetting in everyday life and explored its association with delayed episodic memory recall.ResultsSimilar to results from recent studies of pediatric patients with temporal lobe epilepsy or genetic generalized epilepsy, our pediatric epilepsy patients showed a significantly elevated recall loss over time, although verbal learning, immediate and 30-minute recall was comparable to the matched control group. Additionally, delayed memory recall in patients was moderately associated with their subjective rating of forgetting, as well as with executive functions (verbal fluency and switching) and divided attention.InterpretationWe assume that executive functions play a crucial role in deep memory encoding, facilitating stronger and more enduring memory traces. Given that approximately 20% of epilepsy patients – compared to a healthy reference sample – had a significantly reduced delayed recall and due to the clinical relevance of long-term memory, age-appropriate standard norms for free memory recall after 1-week are desirable.     

Word‐finding difficulties confound performance on verbal cognitive measures in adults with intractable left temporal lobe epilepsy

This study sought to determine if word‐finding difficulties (WFDs), which are common in adults with dominant temporal lobe epilepsy (TLE), are related to performance on verbal cognitive measures, including memory. One hundred six individuals with left TLE and pathologically confirmed mesial temporal sclerosis completed comprehensive preoperative neuropsychological evaluations. Patients were divided into two groups based on the degree of benefit received from phonemic cueing on a confrontation naming task. Cognitive performance was then compared between patients with greater and fewer WFDs. Patients with greater WFDs demonstrated poorer performance on many verbal cognitive measures compared to those with fewer WFDs. In contrast, there were no significant differences between groups on any of the nonverbal cognitive measures. Chi‐square analyses indicated that below average verbal memory performance occurred at a significantly higher rate for patients with greater WFDs (42–46%) as compared to patients with fewer WFDs (18–24%). Results showed that WFDs confound performance on verbal cognitive measures in adult patients with left TLE, particularly on measures with high demands for lexical retrieval. This suggests that when patients have word‐retrieval difficulties, measures of verbal memory and verbal intelligence may be underestimated and potentially lead to misinterpretation of test performance and misinformation regarding risk of declines after surgical resection.     

MRI extrahippocampal volumes and visual memory: correlations independent of MRI hippocampal volumes in temporal lobe epilepsy patients.

Limbic system atrophy and memory dysfunction are common in patients with temporal lobe epilepsy (TLE). However, the relationship between extrahippocampal limbic structures and memory functioning within TLE has received little attention. The present study examined associations of MRI volumetric measurements of the mammillary body, fornix, amygdala, and hippocampus to measures of episodic verbal and visual memory. The Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale were administered to 47 unilateral TLE patients (25 right, 22 left). Normalized right and left MRI volumes were determined for each patient by cursor tracing 1.5 mm slices from 3D-MRI. Significant associations were found between left hippocampal volume and the immediate, delayed, and percent retention scores of the Logical Memory Test; between the left mammillary body volume and the Logical Memory Test delayed and percent retention scores; immediate Visual Reproduction performance was significantly related to the right and left amygdala volumes, and right mammillary body volume; only the right amygdala and right mammillary body volume were associated with the delayed Visual Reproduction trial. However, neither right nor left hippocampal volumes were related to visual memory performance. Multiple limbic system structural volumes were independently associated with verbal and nonverbal memory performance. Results suggest that visual memory, as measured by the Visual Reproduction Test, may be uniquely associated with extrahippocampal volumes in patients with TLE.     

Accelerated long-term forgetting (ALF) and transient epileptic amnesia (TEA): two cases of epilepsy-related memory disorder

Temporal lobe epilepsy (TLE) has long been associated with memory impairment. Recently, two specific forms of memory complaint in this population have been identified: accelerated long-term forgetting (ALF) and transient epileptic amnesia (TEA). This paper presents neuropsychological data (standard neuropsychological tests and experimental measures) on two patients who presented in the epilepsy clinic with seemingly similar subjective reports of profound memory difficulties. This paper illustrates the differences between TEA and ALF. Our focus was on measuring long-term forgetting utilizing a novel visual and verbal test protocol, with responses elicited via verbal prompts over the telephone at intervals up to 30 days. Whereas patient SK had neuropsychological test evidence of problems with learning plus ALF at short and long intervals without clinical evidence of TEA, patient EB had clinically convincing TEA without neuropsychological test evidence of ALF. In particular, SK showed accelerated forgetting while EB did not. This detailed case work develops our understanding of ALF measurement and demonstrates that ALF and TEA can be dissociated.     

Verbal learning and forgetting in patients with temporal lobe epilepsy

Studies comparing non-surgical patients with left or right temporal lobe epilepsy (TLE) have shown irregular differences in verbal learning and memory. We assessed the performance of unoperated patients with epileptogenic temporal lobe lesions or cryptogenic TLE using a selective reminding procedure for the learning of a word list, and five delayed trials for the recall of learned words. On the selective reminding procedure, patients with left TLE were found to be more impaired than those with right TLE and controls, in agreement with the role of the left temporal lobe in verbal learning. The patients with right TLE were more impaired than the controls, possibly due to the semantic organization of the word list The rate of forgetting learned words was similar in the patient and control groups, suggesting that patients with left TLE can normally retain and/or retrieve stored items. These data support the hypothesis that distinct functional systems subserve learning and memory. Comparisons of the patient subgroups with epileptogenic lesions (hippocampal sclerosis or low-grade glioma) and those with cryptogenic TLE did not reveal any significant difference in learning or in memory, suggesting that epileptiform activity could affect verbal performance as a detectable temporal lesion.     

Differential Effects of Left and Right Anterior Temporal Lobectomy on Verbal Learning and Memory Performance

The California Verbal Learning Test (CVLT) was utilized to identify the quantitative and qualitative alterations in verbal learning and memory performance that discriminated between patients following partial resection of the left (dominant) (n = 26) or right (nondominant) (n = 31) temporal lobe. Patients were administered the CVLT preoperatively and 6 months postoperatively, and the differential effects of laterality of resection on verbal learning and memory performance were determined. Following left temporal resection, patients showed significantly more serial clustering, a lower proportion of words recalled from the middle of the list, and more intrusion errors in free recall. Patients who underwent right temporal resection showed significantly greater recall of words from the middle and fewer words from the end of the list, more semantic clustering, and greater ability to recall verbal material after a short delay. These findings suggest that anterior temporal lobectomy (ATL) results in changes in the way verbal material is acquired, and affects the rate of forgetting. Patients who undergo left ATL become more dependent on less effective and efficient learning strategies, and forget the material that they have acquired at a faster rate. The opposite tendencies characterize patients who undergo right ATL.     

Further characterization of patients with amnesia after cardiac arrest: preserved recognition memory

We observed that patients with amnesia after cardiac arrest had preserved recognition memory despite profound loss of recall memory. In the present study, rate of forgetting was measured in six amnesic subjects for both recall and recognition memory of verbal material. The data show that recall decayed significantly faster for the amnesic subjects than for controls, whereas the rate of forgetting for recognition memory was comparable in both groups. Dissociation between recall and recognition performance is a feature of the amnesic syndrome after cardiac arrest.     

Accelerated Long-Term Forgetting Limited to the Recollection Component of Recognition Memory in a Temporal Lobe Epileptic Patient

Accelerated long-term forgetting (ALF) is a frequent finding in patients with temporal lobe epilepsy (TLE). Here we report the case of a TLE patient who complained of marked difficulties in remembering personal events and information even though repeated neuropsychological assessments had failed to detect any deficit on common laboratory memory tests. The patient underwent an experimental investigation that involved estimating recollection and familiarity processes in the performance on verbal and visual recognition tests, over intervals ranging from 10 minutes to 7 days. Results showed accelerated forgetting confined to the recollection component only, which was particularly evident in the verbal test.