Electrical stimulation of the human hippocampus produces verbal intrusions during memory testing

Verbal memory testing was conducted during electrical stimulation of the human hippocampus in 12 epilepsy surgery candidates with unilateral temporal lobe seizure onset. Performance was assessed during baseline, left hippocampal stimulation and right hippocampal stimulation. Verbal intrusion errors were greater during electrical stimulation of the hippocampus contralateral to the seizure focus. These findings suggest that verbal intrusions are related to memory deficits, and that patients with cerebral disease who intrude words from an earlier portion of a learning test are likely to have bilateral cerebral dysfunction.     

The epileptogenic zone in pharmaco‐resistant temporal lobe epilepsy with amygdala enlargement

Aims. Temporal lobe epilepsy with amygdala enlargement (TLE‐AE) has been considered a subtype of TLE. We evaluated the epileptogenic zone in patients with TLE‐AE, who underwent intracranial video‐EEG (ivEEG) and/or intraoperative electrocorticography (ioECoG) as well as epilepsy surgery. Methods. Eleven patients with TLE‐AE were enrolled and investigated based on seizure profile, volumetric MRI, the Wechsler Memory Scale‐Revised (WMS‐R), the location of seizure onset zone (SOZ) and irritative zone (IZ) based on ivEEG (n=8), the location of interictal epileptiform discharges (IEDs) based on ioECoG (11), surgical procedure, and seizure outcome. Results. The mean age at seizure onset was 34.9 years (range: 23–57). The mean duration of seizures was 5.0 years (range: 1–10). The number of AEDs was 2.3 (range: 1–5). The mean seizure frequency was nine per month (range: 1–30/month). All patients presented with focal impaired awareness seizures with (n=9) and without (2) secondary generalized convulsions. Volumetric MRI analysis showed unilateral enlarged amygdala with statistical significance (p<0.01). None of the patients' hippocampi had any abnormality based on MRI. Pre‐operative mean verbal, visual, and delayed recall scores based on the WMS‐R were over 100. The SOZ and IZ were identified in both the amygdala and hippocampus in seven patients and in only the amygdala in one patient based on ivEEG. IEDs were identified in the hippocampus in six patients and in both the amygdala and hippocampus in four patients based on ioECoG. All 11 patients underwent anterior temporal lobectomy, including amygdala resection, with multiple hippocampal transections (dominant hemisphere: seven patients) and resection (non‐dominant hemisphere: three patients). Nine (81.8%) of 11 patients achieved seizure freedom with a mean follow‐up of 26 months (range: 12–47). Post‐operative WMS‐R results did not show any significant deterioration, with a mean follow‐up of 15 months (range: 12–24). The resected amygdala showed no histopathological abnormality. Conclusion. The epileptogenic zone of TLE‐AE involves both the amygdala and hippocampus. ivEEG may be needed to explore the SOZ in normal hippocampus in addition to enlarged amygdala. Amygdala resection and multiple hippocampal transections may control the epileptogenic limbic system and save memory function in patients with TLE‐AE.     

When should a resection sparing mesial structures be considered for temporal lobe epilepsy?

Anteromesial temporal lobectomy (AMTL) is an effective and safe treatment for refractory temporal lobe epilepsy (TLE) caused by hippocampal sclerosis (HS). It is possible that modifications to this procedure could offer improved seizure control or a reduction in functional consequences in some patients. Reviewed here is the issue of when it might be appropriate to perform a resection for TLE that spares the mesial structures, particularly the hippocampus and parahippocampal gyrus. This issue is particularly important for dominant hemipshere TLE and for patients without obvious HS, as these are the patients at greatest risk for verbal memory decline following AMTL. Current evidence suggests that mesial structure-sparing resections may be worth consideration for two types of patients: those with temporal lobe foreign tissue lesions outside the mesial structures, and those with temporal lobe hypometabolism on fluorodeoxyglucose positron emission tomography but a normal MRI. Patients with dual pathology (i.e., HS plus another epileptogenic lesion) are unlikely to benefit from a resection that spares the mesial temporal lobe. There is little evidence to state whether resections of this kind are worthwhile for cryptogenic TLE, or for mesial TLE with preserved memory function. There is a clear need to move beyond the field's present focus on the hippocampus and investigate new approaches to TLE that may minimize the risks of functional consequences in patients without HS.     

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.     

Memory outcome after left anterior temporal lobectomy in patients with expected and reversed Wada memory asymmetry scores

PURPOSE: The ideal candidate for anterior temporal lobectomy surgery shows a Wada memory asymmetry (WMA) score characterized by better memory performance in the hemisphere contralateral to the seizure focus relative to the ipsilateral (surgical) hemisphere. However, some surgical candidates show a reversed WMA or better Wada memory performance in the hemisphere of surgical interest relative to the hemisphere contralateral to the seizure focus. To date, no data are available contrasting memory and seizure outcome for these two Wada groups. The present study compared memory and seizure outcome after left anterior temporal lobectomy (L-ATL) in patients showing expected and reversed WMA scores, and also examined the relationship of the individual hemisphere Wada memory scores for predicting verbal memory outcome after L-ATL. METHODS: We compared 6-month postoperative verbal memory change scores and seizure outcome in L-ATL patients with either an expected (n=12) or reversed WMA (n=9) pattern on Wada memory testing. RESULTS: L-ATL patients showing a reversed WMA score had a poorer verbal memory outcome and poorer seizure control after surgery compared with patients showing a WMA score in the expected direction. CONCLUSIONS: L-ATL patients with a reversed WMA score have a greater risk for memory morbidity and poorer seizure outcome than do patients with a WMA score in the expected direction. The WMA score was the best predictor of memory outcome after L-ATL. When the WMA score is not considered, both individual Wada hemisphere scores (contralateral and ipsilateral) provided significant and independent contribution to predicting postoperative verbal memory functioning. These findings are discussed in the context of the functional reserve and hippocampal adequacy models of memory change after temporal lobectomy.     

Chemical shift imaging spectroscopy and memory function in temporal lobe epilepsy

PURPOSE: Hippocampal neuron loss and associated memory deficits are characteristic of intractable temporal lobe epilepsy (TLE). Proton chemical shift imaging (CSI) spectroscopy is a sensitive tool for detecting neuronal loss. The aim of this study was to investigate the correlation between memory functions and results provided by CSI spectroscopy of the hippocampal structures. METHODS: Ten patients with cryptogenic TLE participated. The study protocol involved both the acquisition of high-spatial-resolution CSI spectroscopy and neuropsychological evaluation, including memory testing and intracarotid sodium amytal test (IAT). The analysis of the CSI data was based on normative data obtained in 30 healthy volunteers. Memory functions were represented by verbal, visual, and general memory indices. RESULTS: A significant correlation was found between CSI spectroscopy of the hippocampal formation and the verbal memory indices for the dominant hemisphere. In addition, there was a significant correspondence of the qualitative judgment "hippocampal pathology indicated by CSI spectroscopy" and both "material specific memory deficit" and "memory deficit in the IAT." CONCLUSIONS: Our results demonstrate that CSI spectroscopy of the hippocampal structures is strongly related to lateralized memory deficits in patients with TLE. This suggests that CSI spectroscopy may be useful in the prediction of postoperative outcome in respect of seizure control and memory.     

Material specific learning during electrical stimulation of the human hippocampus

Material specific learning was assessed during unilateral electrical stimulation of the hippocampus through intracerebrally implanted electrodes in 30 patients with unilateral temporal lobe epilepsy (TLE). Verbal learning significantly decreased in patients with right TLE after stimulation of the left, but not the right, hippocampus. No verbal learning impairment was observed in left TLE patients following stimulation of either hippocampus. Visuospatial memory performance significantly decreased following stimulation of the right hippocampus regardless of the side of seizure onset. Results suggest that the contralateral "nonepileptic" hippocampus does not assume the material specific mnestic functions of the dysfunctional hippocampus associated with longstanding epilepsy.     

Crossed aphasia in a patient with complex partial seizures: evidence from intracarotid amobarbital testing, functional cortical mapping, and neuropsychological assessment.

We report a right-handed patient who became transiently aphasic following a right temporal lobectomy for control of intractable complex partial seizures. Preoperative intracarotid amobarbital testing revealed right-hemisphere language dominance, although bilateral language representation was present. Memory testing during unilateral electrical hippocampal simulation with depth electrodes indicated reliance on left-hemisphere mesial temporal lobe structures for verbal memory. Functional mapping for language during surgery established several right perisylvian regions that, when stimulated, produced speech arrest and/or paraphasic substitution. One-year follow-up neuropsychological assessment demonstrated an increase in verbal learning and decrease in visual memory, a pattern associated with patients who have undergone right temporal lobectomy. These data demonstrate that (1) right cerebral language dominance can be observed when ipsilateral seizure onset is present (2) verbal memory and language dominance are not necessarily linked, and (3) some reported cases of crossed aphasia may in fact have bilateral language representation.     

Neuropsychological change following gamma knife surgery in patients with left temporal lobe epilepsy: a review of three cases

Gamma knife surgery (GKS) is a radiation procedure recently used in the treatment of temporal lobe epilepsy (TLE). Preliminary studies have shown significant seizure reductions in patients 8-26 months postprocedure; however, little is known about the effect of GKS on cognitive functioning in TLE. We report neuropsychological data on three patients with left TLE and MRI evidence of hippocampal sclerosis who underwent GKS. Two models for assessing cognitive change, reliable change indices and regression-based norms for change, were used to measure preoperative versus 13- to 27-month postoperative cognitive change. Results revealed a significantly long delayed verbal memory decline on one measure following GKS. No patient declined on measures of IQ, visual memory, or language. Radiation-induced edema was present at the time of testing in all three patients, which may have affected verbal memory performance. While preliminary, these data suggest that GKS offers a less invasive option to anterior temporal lobectomy, but may produce neuropsychological changes similar to those produced by left anterior temperol lobectomy up to 2 years post-GKS treatment.     

Impairment of recent memory after temporal lesions in man

Five cases of recent memory impairment following unilateral temporal lesions are described. In three patients auditory and visual recent memory disturbances were produced by the epileptogenic lesion in one hippocampal zone giving afterdischarges in both temporal lobes. In all these cases recent memory deficit cleared completely after unilateral temporal lobectomy when EEG examinations showed no more abnormalities in the contralateral temporal region. In one patient in whom left temporal lobectomy was performed because of a malignant glioma grave impairment of auditory and visual recent memory was revealed 6 months after operation when the tumour began to generate EEG abnormalities in both temporal lobes. The last patient showed selective impairment of verbal recent memory following strict unilateral lesion in the left hippocampal zone.     

Intracarotid amobarbital procedure and prediction of postoperative memory in patients with left temporal lobe epilepsy and hippocampal sclerosis

PURPOSE: Although temporal lobe epilepsy (TLE) patients with dominant hemisphere hippocampal sclerosis generally have good cognitive outcome after anterior temporal lobectomy (ATL), a minority of patients experience at least mild post-ATL decline on one or more standardized measures of episodic and semantic memory. The goal of this investigation was to determine whether memory outcome in this group could be predicted from preoperative intracarotid amobarbital procedure (IAP) recognition memory scores. METHODS: Data from 22 left TLE patients were studied retrospectively. All were left hemisphere language dominant and had IAP scores for each hemisphere, a significant degree of pathology-confirmed left hippocampal sclerosis (HS+), and no positive MRI findings other than atrophy. Cognitive outcome status was represented by the number of pre- to post-ATL declines across three tests, as defined by 90th percentile Reliable Change Index (RCI) criteria. RESULTS: Only 14% of the sample exhibited decline on more than one memory test. Low right IAP (left hemisphere injection) scores and relatively high preoperative cognitive ability and age at surgery predicted a greater risk of post-ATL memory decline. CONCLUSIONS: A minority of left TLE HS+ patients experience at least a mild degree of RCI-defined decline in episodic or semantic memory after ATL. The right hemisphere IAP memory score, which reflects the functional reserve of the contralateral hemisphere, can help predict the risk of postoperative memory decline for TLE patients in whom HS+ is likely based on the presence of hippocampal atrophy on MRI or early age of seizure onset.     

Crossed aphasia in a patient with complex partial seizures: Evidence from intracarotid amobarbital testing,functional cortical mapping,and neuropsychological assessment

Abstract

We report a right-handed patient who became transiently aphasic following a right temporal lobectomy for control of intractable complex partial seizures. Pre-operative intracarotid amobarbital testing revealed right-hemisphere language dominance, although bilateral language representation was present. Memory testing during unilateral electrical hippocampal simulation with depth electrodes indicated reliance on left-hemisphere mesial temporal lobe structures for verbal memory. Functional mapping for language during surgery established several right perisylvian regions that, when stimulated, produced speech arrest and/or paraphasic substitution. One-year follow-up neuropsychological assessment demonstrated an increase in verbal learning and decrease in visual memory, a pattern associated with patients who have undergone right temporal lobectomy. These data demonstrate that (1) right cerebral language dominance can be observed when ipsilateral seizure onset is present (2) verbal memory and language dominance are not necessarily linked, and (3) some reported cases of crossed aphasia may in fact have bilateral language representation.     

Memory following intracarotid amobarbital injection contralateral to hippocampal damage

We examined the relationship between memory performance and hippocampal damage in temporal lobe epileptics undergoing the intracarotid amobarbital sodium procedure (IAP). Overall memory performance in the course of IAP was correlated with seizure lateralization. The hemisphere of seizure focus had impaired IAP memory in 63% (19/30) of the patients. The IAP memory performance following perfusion of the hemisphere contralateral to severe hippocampal lesions was impaired in five of six patients. These patients also exhibited hypometabolism of the impaired temporal lobe as determined independently by positron emission tomography. The single patient with a severely damaged hippocampus who did not demonstrate IAP memory impairment with contralateral hemisphere injection did not exhibit perfusion of the ipsilateral posterior cerebral artery with amobarbital. Memory performance following intracarotid amobarbital injection contralateral to a less severely damaged hippocampus was impaired in 14 of 24 patients and was not related to extent of hippocampal damage, temporal lobe hypometabolism of labeled glucose, perfusion of the ipsilateral posterior cerebral artery, hemispheric language dominance, or order of injection. These results indicate that impaired memory performance during IAP may reflect severe hippocampal damage and/or epileptogenic abnormality.     

Naming outcomes of anterior temporal lobectomy in epilepsy patients: a systematic review of the literature

Anterior temporal lobectomy (ATL) is the standard surgical treatment for medically intractable temporal lobe epilepsy (TLE). While seizure outcome is favorable, cognitive outcomes are a concern, particularly in respect of memory and naming. A systematic review of the literature on the naming outcomes of ATL is presented in this article. Searches were conducted on PubMed and PsycInfo, yielding a total of 93 articles, 21 of which met inclusion criteria. Declines in visual naming are common following ATL in the dominant hemisphere, and particularly, for naming living stimuli or famous faces. The Boston Naming Test (BNT) declines by a mean of 5.8 points, exceeding the Reliable Change Index (RCI). There are no reports of deficits in auditory naming following ATL, despite the fact that auditory naming has shown to be a more sensitive measure of dysnomia than the BNT in TLE patients. The absence of structural hippocampal pathology and late-onset epilepsy are the strongest predictors of naming decline. Recommendations are made for further study.     

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 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.     

Bilateral reductions of hippocampal volume, glucose metabolism, and Wada hemispheric memory performance are related to the duration of mesial temporal lobe epilepsy

In refractory temporal lobe epilepsy (TLE) temporal lobe structures and functions are continuously or intermittently affected by abnormal brain electrical events, noxious neurochemical agents, and metabolic disturbances. There is conflicting evidence regarding the relationship between the duration of refractory mesial TLE and quantitative measures of temporal lobe functions and volumes of the hippocampi. Twenty patients (aged 28 ± 7 years, 14 males) with an initial precipitating injury before the age of 5 years were subjected to high-resolution magnetic resonance imaging, fluoro-2-deoxy-d-glucose positron-emission tomography (PET), and the Wada test. We investigated whether the duration of unilateral refractory TLE (12 left, 8 right) affects hippocampal volume, glucose metabolism, or Wada hemispheric memory performance. Ipsilateral to the epileptogenic zone the hippocampal volume, metabolism, and Wada hemispheric memory performance were reduced compared to the corresponding contralateral measures. The duration of epilepsy controlled for age at investigation, side of seizure origin, underlying cause, and sex were negatively correlated with ipsi- and contralateral hippocampal volume, hippocampal metabolism, and Wada hemispheric memory performance. Moreover, ipsilateral Wada hemispheric memory performance and contralateral hippocampal glucose metabolism were correlated with the frequency of habitual seizures. Refractory TLE seems to be associated with a slow but ongoing bilateral temporal lobe damage. These cross-sectional results require verification by longitudinal studies carried out over a period of more than two decades. Received: 30 July 1998 Received in revised form: 16 March 1999 Accepted: 24 April 1999     

Poor presurgical performance on both verbal and visual memory measures is associated with low risk for memory decline following left temporal lobectomy for intractable epilepsy

Studies have shown a lower risk for verbal memory decline following dominant anterior temporal lobectomy (ATL) among patients with poor, presurgical verbal memory scores. It is unclear however, if the risk of decline is increased in patients who also have reduced visual memory. Objective and subjective memory outcome following left ATL was examined in twelve patients with reduced presurgical visual and verbal memory scores. Only one patient demonstrated a meaningful decline in memory scores, with a decline in visual memory following surgery. Presurgically, this patient demonstrated poor memory bilaterally on Wada testing and small discrepancy in hippocampal volumes. She was also one of two patients who continued to have seizures post-surgery. This preliminary study suggests that patients with unilateral, left TLE and poor verbal and visual memory are unlikely to show meaningful memory declines following left ATL, particularly if they demonstrate expected patterns on Wada testing, hippocampal volume discrepancy (left < right), and postsurgical seizure-freedom.     

Adequacy of language function and verbal memory performance in unilateral temporal lobe epilepsy.

We examined adequacy of language functions, their influence on verbal learning and memory performance, and the relative effects of language function and laterality of seizure focus on the memory performance of 99 left-hemisphere dominant patients with invasively verified epilepsy of left (N = 47) or right (N = 52) temporal lobe origin. Patients with left temporal lobe epilepsy (TLE) scored significantly lower than the right TLE group on several aphasia battery subtests (Visual Naming, Sentence Repetition, Token Test, Reading Comprehension, Aural Comprehension). Adequacy of language function (nominal speech) was significantly related to verbal learning and memory performance for both left and right TLE groups. Finally, comparison of the predictive significance of laterality of TLE and adequacy of language function indicated that language functions (Visual Naming and Aural Comprehension), but not laterality of TLE, were significant predictors for verbal learning and memory performance. It is concluded that: 1) adequacy of basic language functions is particularly compromised in left TLE, 2) there is a significant relationship between adequacy of language function and several aspects of verbal learning and memory ability in both left and right temporal lobe groups, and 3) clinical assessment and theoretical models of memory need to consider these relationships.     

Memory deficits after resection from left or right anterior temporal lobe in humans: a meta-analytic review

PURPOSE: Memory deficits in epileptic patients have been found in some, but not all studies assessing the effects of side of seizures and resection from a temporal lobe on cognitive performance. The purpose of this study was to provide a quantitative review of previous studies on this issue. METHODS: Based on conventional meta-analytic procedures, we identified 33 studies that assessed verbal and nonverbal memory performance before and after anterior temporal lobectomy. The Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale were used. These studies were then subjected to two levels of analyses: (a) vote-counting procedure, and (b) effect-size calculations and comparisons. RESULTS: Overall, the data confirmed previous findings that verbal memory tasks are sensitive to left hemisphere dysfunction. The efficacy of a "nonverbal" task for tapping function in the nondominant (right) hemisphere was not confirmed, although a trend supporting this speculation was observed. With regard to the comparison of changes in verbal and nonverbal memory before and after resection from a temporal lobe, a clear trend was observed for decline in verbal memory function after resection from the left, especially significant for immediate verbal recall. A trend for contralateral improvement on nonverbal memory also was observed. The pattern of memory change after resection from the right temporal lobe was less clear. CONCLUSIONS: The findings of this study suggest that side of epileptic seizure and surgical resection from a temporal lobe affect verbal memory functions. The relations between the laterality of epileptic seizure, surgical resection from the temporal lobe, and nonverbal memory are to be verified by further research.