Cognitive Consequences of Two-Thirds Anterior Temporal Lobectomy on Verbal Memory in 144 Patients: A Three-Month Follow-Up Study

Previous studies have shown that left temporal lobectomy for intractable epilepsy can lead to verbal memory deficits. However, patients with left temporal lobe epilepsy (LTLE) frequently have impaired verbal memory preoperativel. The present analysis of 144 patients who underwent temporal lobe resections for either left (n = 68) or right (n = 76) temporal lobe epilepsy (LTLE, RTLE) addressed the questions of (a) whether a left two-thirds anterior temporal lobectomy (ATL) increases deficits in these qualitative aspects of verbal memory already impaired preoperatively, and (b) whether other aspects of verbal memory are additionally affected. We also evaluated possible determinants of preoperative abilities and postoperative changes, using multiple regression analysis. Preoperatively, patients with LTLE differed from patients with RTLE only in poorer performance on measures of long-term consolidation/retrieval (delayed recall). This was related to hippocampal pathology and seizure severity. Only left temporal lobe resections resulted in significant deterioration in verbal learning and memory. Acquisition over learning trials and recognition deteriorated most markedly, whereas performance in long-term consolidation/retrieval showed only minor changes. Preoperative performance levels, chronological age, the extent of the en bloc resection, preoperative performance on figural memory, and preoperative seizure severity were valuable determinants of postoperative changes in acquisition and recognition. In contrast, changes in consolidation/retrieval related only to preoperative ability. Left two-thirds ATL leads to new impairment in addition to preexisting memory deficits. The finding that left temporal lobectomy affects verbal acquisition and recognition more than long-term consolidatiodretrieval, including the different determinants of these changes, most likely reflects the differential effects of surgery on mesial temporal and neocortical temporal functions.     

Verbal Memory in Newly Diagnosed Patients and Patients with Chronic Left Temporal Lobe Epilepsy

The objective of this study was to evaluate verbal memory in newly diagnosed and chronic left temporal lobe epilepsy (LTLE). Verbal memory performance of 39 newly diagnosed, previously untreated adult patients with LTLE and 16 patients with chronic LTLE, as well as 46 healthy controls, was analyzed. The patients with newly diagnosed and chronic LTLE had impaired verbal memory performance compared with normal controls. Memory performance was more affected in chronic LTLE. However, preliminary data from 5-year follow-up of 20 newly diagnosed LTLE patients did not show any deterioration in verbal memory performance. The memory impairment was not associated with the etiology of epilepsy or the hippocampal volumes, but was associated with early onset of epilepsy in LTLE and with secondarily generalized seizure type in newly diagnosed LTLE. The results of this study show that verbal memory is impaired not only in chronic LTLE but also in newly diagnosed, untreated LTLE. This suggests that the memory problems observed in patients with chronic LTLE cannot be attributed solely to medication effects or the chronic effects of recurrent seizures.     

Pseudoword and Real Word Memory in Unilateral Temporal Lobe Epilepsy

Recognition memory for pronounceable pseudowords (PWs), real words, and degraded photographs of unfamiliar faces, was examined in 45 patients with unilateral temporal lobe epilepsy (TLE), before and after Anterior Temporal Lobectomy, to test predictions from two accounts of hemispheric differences in memory functioning: (1) The ‘material-specific’ account predicts that left TLE (LTLE) patients would be impaired in memory for both familiar (real words) and unfamiliar (PWs) verbal stimuli, while memory for novel complex visual stimuli (unfamiliar faces) would be impaired in right TLE (RTLE) patients. (2) The ‘familiarity’ account predicts that memory for familiar stimuli (such as words) will be impaired in LTLE patients, while memory for both linguistic and nonlinguistic unfamiliar stimuli should be disrupted in RTLE patients. Results were consistent with the ‘material-specific’ hypothesis suggesting that both familiar and unfamiliar linguistic stimuli are processed for memory in the left medial temporal lobe (MTL), whereas unfamiliar nonverbal stimuli are processed for memory in the right MTL.     

Pseudoword and real word memory in unilateral temporal lobe epilepsy

Recognition memory for pronounceable pseudowords (PWs), real words, and degraded photographs of unfamiliar faces, was examined in 45 patients with unilateral temporal lobe epilepsy (TLE), before and after Anterior Temporal Lobectomy, to test predictions from two accounts of hemispheric differences in memory functioning: (1) The 'material-specific' account predicts that left TLE (LTLE) patients would be impaired in memory for both familiar (real words) and unfamiliar (PWs) verbal stimuli, while memory for novel complex visual stimuli (unfamiliar faces) would be impaired in right TLE (RTLE) patients. (2) The 'familiarity' account predicts that memory for familiar stimuli (such as words) will be impaired in LTLE patients, while memory for both linguistic and nonlinguistic unfamiliar stimuli should be disrupted in RTLE patients. Results were consistent with the 'material-specific' hypothesis suggesting that both familiar and unfamiliar linguistic stimuli are processed for memory in the left medial temporal lobe (MTL), whereas unfamiliar nonverbal stimuli are processed for memory in the right MTL.     

Resting state functional connectivity of the hippocampus associated with neurocognitive function in left temporal lobe epilepsy

The majority of patients with temporal lobe epilepsy (TLE) experience disturbances of episodic memory from structural damage or dysfunction of the hippocampus. The objective of this study was to use functional Magnetic Resonance Imaging (fMRI) to identify regions where resting state connectivity to the left hippocampus (LH) is correlated with neuropsychological measures of verbal memory retention in TLE patients. Eleven left TLE (LTLE) patients and 15 control subjects participated in resting state fMRI scans. All LTLE patients underwent neuropsychological testing. Resting state functional connectivity maps to the LH were calculated for each patient, and subsequently used in a multiple regression analysis with verbal memory retention scores as a covariate. The analysis identified brain regions whose connectivity to the LH was linearly related to memory retention scores across the group of patients. In LTLE patients, right sided (contralateral) clusters in the precuneus and inferior parietal lobule (IPL) exhibited increased connectivity to the LH with increased memory retention score; left sided (ipsilateral) regions in the precuneus and IPL showed increased connectivity to the LH with decreased retention score. Patients with high memory retention scores had greater connectivity between the LH–right parietal clusters than between the LH–left parietal clusters; in contrast, control subjects had significantly and consistently greater LH–left hemisphere than LH–right hemisphere connectivity. Our results suggest that increased connectivity in contralateral hippocampal functional pathways within the episodic verbal memory network represents a strengthening of alternative pathways in LTLE patients with strong verbal memory retention abilities. Hum Brain Mapp 35:735–744, 2014. © 2012 Wiley Periodicals, Inc.     

Bilateral hemispheric alteration of memory processes in right medial temporal lobe epilepsy

OBJECTIVE: Functional MRI (fMRI ) was used to investigate right medial temporal lobe epilepsy (RTLE) effects on verbal memory. METHODS: BOLD fMRI data were collected from seven right sided MTLE patients (RTLE) and compared with the data previously acquired from seven left sided MTLE patients (LTLE) and 10 control subjects. Twenty two contiguous images covering the whole brain were acquired using an EPI echoplanar sequence. Subjects were instructed to learn a list of 17 words, and to recall it immediately and at 24 hours interval. Group analyses were performed using SPM96. RESULTS: RTLE patients retrieval performances were significantly impaired as compared with the performance of control subjects. As compared with control subjects and LTLE patients, RTLE patients exhibited a different pattern of hemispheric activations and a global decrease in left hemisphere functional activity. CONCLUSION: MTLE cannot be considered as a model of pure well lateralised hippocampal dysfunction. The verbal memory impairment depicted in RTLE patients may be considered as the witness of a bilateral impairment of the neuroanatomical circuits subserving memory.     

Verbal learning differences in epileptic patients with left and right temporal lobe foci - a pharmacologically induced phenomenon?

A total of 27 patients with medically intractable complex partial seizures has been investigated for effects of anticonvulsant drugs on mental abilities, particularly on verbal memory performance. Fourteen patients with right (RTLE) and 13 with left (LTLE) temporal lobe epilepsy have been tested with a word list learning paradigm under the conditions of full and reduced anticonvulsant medication. Memory performance has significantly improved with drug reduction, however only for the LTLE group. In addition, significant group differences for verbal memory between LTLE and RTLE subjects under full medication have completely disappeared with drug reduction. Finally this investigation demonstrates, that very specific and circumscribed steps of verbal memory processing, particularly retrieval abilities after interference, are affected by anticonvulsants. These findings underline the importance of pharmacological effects on cognition and suggest to reevaluate their relevance compared to other contributing factors.     

Stimulus type affects Wada memory performance

The effects of amytal injection side, seizure focus laterality, and stimulus type (real and line-drawn objects, printed words, and faces) on recognition memory were studied during the Wada procedure. To-be-remembered stimuli were presented during cerebral anesthesia to 35 patients with left temporal lobe epilepsy (LTLE) and 28 patients with right temporal lobe epilepsy (RTLE), all with left hemisphere language dominance. In both groups, recognition of real and line-drawn objects was best after anesthetization of the lesional hemisphere. Recognition of faces was poor after either injection in patients with RTLE, but only after right injection in patients with LTLE. Conversely, recognition of words by patients with LTLE was impaired equally after either injection, but more so after left than right injection in patients with RTLE. The findings suggest that (1) real and line-drawn objects are "dually encoded" and memory accuracy depends on seizure focus laterality, and (2) accuracy in recognition of words and faces is related to seizure focus laterality, but may also depend on the language dominance of the hemisphere being assessed.     

Differential contributions of the hippocampus and rhinal cortices to verbal memory in epilepsy

The present study explored the left mesial temporal lobe correlates of verbal memory in patients with temporal lobe epilepsy (TLE). An index of structural integrity, T2 relaxation time, was measured bilaterally in three mesial temporal regions of interest, and correlated with measures of verbal memory. The acquisition of verbal arbitrary relational material was most strongly associated with left perirhinal T2 signal. In contrast, verbal memory consolidation was related to T2 signal in the left hippocampus. Our findings suggest a key role for the left perirhinal region in the uptake of arbitrary linkages that underlie new learning. The hippocampus, on the other hand, is important for protecting newly learned information from the effects of interference. This double dissociation provides a neurocognitive account of the left mesial temporal memory syndrome.     

Face memory in MRI-positive and MRI-negative temporal lobe epilepsy

PURPOSE: Effects of MRI-positive (MRI(+)) as compared to MRI-negative (MRI(-)) temporal lobe epilepsy (TLE) on face memory are not yet known. METHODS: We studied 24 MRI(-) (11 right/13 left) and 20 MRI(+) (13 right/7 left) TLE patients, 12 generalized epilepsy patients, and 12 healthy subjects undergoing diagnostic workup with 24-72-h Video-EEG-monitoring. Twenty faces were shown, and had to be recognized from 40 faces immediately and after a 24-h delay. RESULTS: MRI(+) and MRI(-) right TLE (RTLE) patients showed deficits in face recognition compared to controls or generalized epilepsy, consistent with right temporal lobe dominance for face recognition. MRI(+) RTLE patients had deficits in both immediate and delayed recognition, while MRI(-) RTLE patients showed delayed recognition deficits only. The RTLE groups showed comparable delayed recognition deficits. Separate analyses in which the MRI(+) group included patients with hippocampal sclerosis only, did not alter results. Furthermore, MRI(-) RTLE had a worse delayed recognition than MRI(-) left TLE (LTLE). On the other hand, MRI(+) RTLE did not differ from MRI(+) LTLE in delayed recognition. Combining MRI(-) and MRI(+) TLE groups, we found differences between RTLE and LTLE in delayed, but not immediate face recognition. CONCLUSIONS: Our results suggest that a delayed recognition condition might be superior to immediate recognition tests in detecting face memory deficits in MRI(-) RTLE patients. This might explain why former studies in preoperative patients did not observe an immediate face recognition dominance of the right temporal lobe when combining MRI(-) and MRI(+) TLE patients. Our data further point to an important role of the right mesial temporal region in face recognition in TLE.     

Memory rehabilitation and brain training for surgical temporal lobe epilepsy patients: a preliminary report

The short term impact of a memory rehabilitation programme on verbal memory test performance and subjective ratings of memory in everyday life was assessed in healthy controls and left temporal lobe epilepsy (LTLE) surgical patients. The intervention involved training in the use of external and internal memory support strategies. Half of the sample in addition undertook computerised brain training exercises as homework. LTLE patients were seen either before surgery or 3-6 months after their operation. Improvements in verbal memory were observed in both groups. An effect of brain training was recorded but this did not occur in a consistent direction. Subjective ratings of memory indicated improvements that were significant for the LTLE group but not the controls. Positive changes in the memory outcome measures were associated with improvements in mood. Pre-operative memory rehabilitation was not associated with better outcomes than post-operative intervention. Further research is needed to explore the persistence of the changes observed and to explore if pre-operative rehabilitation offsets post-operative memory decline.     

Circumscribed improvement of cognitive performance in temporal lobe epilepsy patients with intractable seizures following reduction of anticonvulsant medication

During the presurgical evaluation of patients with intractable complex partial seizures, neuropsychometric testing was performed under conditions of full and reduced medication in order to determine the influence of anticonvulsants on cognitive performance. While attentional parameters remained completely unchanged, verbal memory performance improved significantly under reduced medication in patients with left temporal lobe epilepsy (LTLE) only, whereas patients with right temporal lobe epilepsy (RTLE) did not differ significantly under both conditions. However, a reverse, but not significant, pattern with improvement of nonverbal memory under reduced medication was only observed in RTLE subjects. The data suggest circumscribed effects of anticonvulsant medication on cognition in relation to the localization of the seizure focus.     

Asymmetries in the Effect of Side of Seizure Onset on Recognition Memory Following Intracarotid Amobarbital Injection

Summary: Purpose : To assess inter hemispheric differences in recognition memory for objects during the intracarotid amobarbital sodium procedure (IAP).
Methods : The recognition memory for real objects of patients with either right (RTLE, n = 28) or left (LTLE; n = 22) temporal lobe epilepsy was assessed at baseline, and after left and right intracarotid amobarbital sodium injection.
Results : There were no differences between groups on baseline performance. Performance following injection ipsilateral to the side of seizure focus was relatively lower for the LTLE as compared with the RTLE group, but this difference did not reach statistical significance. However, performance following injection contralateral to the side of seizure focus was significantly lower for the RTLE as compared with the LTLE group. Within-group differences in performance after ipsilateral as compared with contralateral injection were significant for the RTLE but not the LTLE group. The difference in inter hemispheric asymmetry in IAP memory performance between RTLE and LTLE groups was reflected in decreased ability to classify LTLE patients as compared with RTLE patients about side of seizure onset, using a clinically applicable decision rule.
Conclusions : Recognition memory during the IAP for real objects, simultaneously named and presented visually during encoding, is mediated effectively by both the left and right hemisphere when there is no seizure focus present. However, memory appears to be more vulnerable to the presence of a seizure focus in the right as compared with the left hemisphere.     

Effect of age of onset of temporal lobe epilepsy on the severity and the nature of preoperative memory deficits

The nature and severity of pre-operative memory deficits observed in unilateral temporal lobe epilepsy depend upon a number of variables. Among these variables, age of seizure onset seems to be important. The age at which the lesion is sustained could modify the normal functional organization of the brain. Many studies have examined the effect of age of onset on the severity of memory deficits but have seldom focused on the nature of such deficits (verbal/nonverbal) as a function of epileptic focus laterality. This study investigates the effect of age of onset on the nature and severity of memory impairments. Fifty-six epileptics with unilateral temporal lobe epilepsy and 20 normal subjects were administered a neuropsychological evaluation. Four groups of patients were constituted: left or right temporal lobe epilepsy with early (0-5 years) or late (10 years and over) age of seizure onset. The early group showed major verbal and nonverbal memory deficits. The late group presented minor specific deficits: essentially verbal deficits with left temporal lobe seizures and nonverbal deficits with right temporal lobe seizures. These results may be interpreted in the framework of ontogenesis theories of hemispheric specialization.     

Relationships between epilepsy-related factors and memory impairment

OBJECTIVES: In this study, we will explore the effect of epilepsy-related factors such as: 'type of epilepsy, 'site and side of focus localisation' and 'age at onset', as well as four seizure-related factors: 'years with continuing seizures', 'seizure type' and 'seizure frequency', and the treatment factor 'adverse effects of the medication', on memory impairment. Additionally, we explored whether these epilepsy factors are related to different aspects of memory, i.e. short-term recall vs long-term recall, learning, and verbal memory vs non-verbal memory. MATERIAL AND METHODS: A total of 252 patients with epilepsy and subjective memory complaints were consecutively included from the three epilepsy centres in the Netherlands. To assess memory functions the Wechsler Memory Scale-Revised (WMS-r), and the Dutch version of the California Verbal Learning Test for verbal list learning, was administered. RESULTS: A multivariate analysis of variance (MANOVA) did not show statistically significant effects of the epilepsy factors on memory for the total study sample. For the patients with a unilateral epileptogenic focus in the temporal lobes, MANOVA showed statistically significant effects of lateralisation, with most impairment for patients with left temporal lobe epilepsy and, independently, seizure frequency and 'years with seizures'. CONCLUSION: We may conclude that epilepsy-related dysfunctions in the temporal lobe are the dominant risk factor for developing memory problems, specifically verbal memory problems (verbal learning and problems consolidating verbal information), with more severe impairments with continuing seizures and when seizure frequency is high.     

Application of signal detection theory to verbal memory testing to distinguish patients with psychogenic nonepileptic seizures from patients with epileptic seizures

Distinguishing psychogenic nonepileptic seizures (PNES) from epileptic seizures (ES) is a difficult task that is often aided by neuropsychological evaluation. In the present study, signal detection theory (SDT) was used to examine differences between these groups in neuropsychological performance on the Wechsler Memory Scale, Third Edition, Word List Test (WMS-III WLT). The raw WMS-III WLT scores on this task failed to discriminate the two groups; however, with the use of SDT, patients with PNES were found to have a negative response bias and increased memory sensitivity as compared with patients with ES. When patients with left (LTLE) and right (RTLE) temporal lobe epilepsy were compared, the patients with LTLE demonstrated decreased memory sensitivity but a similar response bias as compared with the patients with RTLE. Memory impairment in patients with PNES may be related to faulty decision-making strategies, rather than true memory impairment, whereas memory performance differences between the LTLE and RTLE groups are likely related to actual differences in memory abilities.     

The effects of temporal lobe epilepsy on scene encoding

Forty-four patients with temporal lobe epilepsy (TLE) (25 left) and 40 healthy control participants performed a complex visual scene-encoding fMRI task in a 4-T Varian scanner. Healthy controls and left temporal lobe epilepsy (LTLE) patients demonstrated symmetric activation during scene encoding. In contrast, right temporal lobe (RTLE) patients demonstrated left lateralization of scene encoding which differed significantly from healthy controls and LTLE patients (all p ≤ .05). Lateralization of scene encoding to the right hemisphere among LTLE patients was associated with inferior verbal memory performance as measured by neuropsychological testing (WMS-III Logical Memory Immediate, p = 0.049; WMS-III Paired Associates Immediate, p = 0.036; WMS-III Paired Associates Delayed, p = 0.047). In RTLE patients, left lateralization of scene encoding was associated with lower visuospatial memory performance (BVRT, p = 0.043) but improved verbal memory performance (WMS-III Word List, p = 0.049). These findings indicate that, despite the negative effects of epilepsy, memory functioning is better supported by the affected hemisphere than the hemisphere contralateral to the seizure focus.     

Inferior temporal stream for word processing with integrated mnemonic function.

The participation of the inferior temporal cortex in visual word perception and recognition raises several questions: Is there a directed processing stream proceeding anteriorly by continuous cortical processing? How fast are words processed within such an inferior temporal stream? Does this stream support implicit or explicit memory? To answer these questions, we analyzed the spatio-temporal relationship of event-related potentials, recorded directly from the inferior temporal cortex in epilepsy patients performing a continuous visual word recognition paradigm. Event-related potentials elicited an inferior temporal positivity in a strip along the left collateral sulcus. This potential exhibited a linear (r = 0.74) peak latency progression from posterior to anterior inferior temporal regions (approximately 15 cm/sec), indicating a directed, intracortical processing stream. Peak amplitudes and latencies showed reliable old/new effects with smaller amplitudes and shorter latencies for old as opposed to new words. Although the amplitude-old/new-effect occurred for all repeated words (e.g., implicit memory), the latency-old/new-effect occurred for correctly recognized old words only (e.g., explicit recognition). These results seem to dissociate two distinct mnemonic processes. The graded decrease of mean ITP peak amplitudes and latencies, however, does not allow us to exclude a single trace model as assumed for explicit recognition memory based on familiarity (Mandler [1980]: Psychol Rev 87:252-271). Regardless whether there is a dissociation between implicit and explicit memory in inferior temporal cortex or not, our findings are in accordance with an integrated inferior temporal processing stream for words that performs continuously semantic and mnemonic operations supporting both implicit and explicit memory.     

Memory Tests Distinguish Between Patients with Focal Temporal and Extratemporal Lobe Epilepsy

We examined the ability of preoperative memory performance to distinguish between patients who had been diagnosed as having left (LTLE, n = 31), right (RTLE, n = 37), and extra-(ETLE, n = 17) temporal lobe focal epilepsy. All patients eventually underwent surgical resections. Analyses indicated that the ETLE group performed better than the RTLE group on nonverbal memory measures and better than the LTLE group on verbal memory measures. Discriminant function analyses indicated that use of a combination of measures that assess different aspects of memory were of significant value in distinguishing between patients with focal TLE and ETLE. This approach, as compared the use of single measures, improved classification rates of all three groups. The best single predictor of group membership, an index of verbal learning, yielded a 47% overall correct classification rate, with sensitivities ranging from 25 to 59%, and performed at worse than chance levels in classifying RTLE patients. A multivariate approach, which included an index of verbal and nonverbal learning, incidental nonverbal memory, and consolidation of organized and rote verbal material, yielded a 65% correct classification rate, with sensitivities ranging from 57 to 75%. This compares favorably with other noninvasive techniques for lateralizing epileptogenic lesions.     

Subtemporal hippocampectomy preserving the basal temporal language area for intractable mesial temporal lobe epilepsy: preliminary results

PURPOSE: Decline in verbal memory as a surgical complication remains an unresolved problem in mesial temporal lobe epilepsy. Some areas in the temporal lobe associated with the language function, often including the basal temporal language area, have been removed or transected by conventional surgical procedures. The authors defined the basal temporal language area and removed only the epileptogenic zone with a subtemporal approach. METHODS: The basal temporal language area was evaluated by using long-term subdural electrodes in five patients with language-dominant-side mesial temporal lobe epilepsy. While preserving this area, the hippocampus and the parahippocampal gyrus were removed by using a combined subtemporal, transventricular, transchoroidal fissure approach. Verbal memory performance was assessed with the Wechsler Memory Scale-Revised (WMS-R) before and after the operation. RESULTS: The basal temporal language area, defined as a part of the inferior temporal gyrus, the fusiform gyrus, and the parahippocampal gyrus, was spared by entering the temporal horn via collateral sulcus. Verbal memory was significantly improved by 3 months and 1 year after the operation. CONCLUSIONS: In language-dominant-side mesial temporal lobe epilepsy, preserving the basal temporal language area would have potential to improve verbal memory outcomes after removal of the epileptogenic zone.