Medial Temporal Lobe Epilepsy Patients Research Articles

How much are clinical fMRI reports influenced by standard postprocessing methods? An investigation of normalization and region of interest effects in the medial temporal lobe

Recent evidence has indicated that standard postprocessing methods such as template-based region of interest (ROI) definition and normalization of individual brains to a standard template may influence final outcome of functional magnetic resonance imaging investigations. Here, we provide the first comprehensive investigation into whether ROI definition and normalization may also change the clinical interpretation of patient data. A series of medial temporal lobe epilepsy patients were investigated with a clinical memory paradigm and individually delineated as well as template-based ROIs. Different metrics for activation quantification were applied. Results show that the application of template-based ROIs can significantly change the clinical interpretation of individual patient data. This relates to sensitivity for brain activation and hemispheric dominance. We conclude that individual ROIs should be defined on nontransformed functional data and that use of more than one metric for activation quantification is beneficial.

A functional MRI study of language networks in left medial temporal lobe epilepsy

Purpose The purpose of this study was to investigate the abnormality of language networks in left medial temporal lobe epilepsy (MTLE) using fMRI. Materials and methods Eight patients with left MTLE and 15 healthy subjects were evaluated. An auditory semantic judgment (AJ) paradigm was used. The fMRI data were collected on a 3T MR system and analyzed by AFNI (analysis of functional neuroimages) to generate the activation map. Results Behavioral data showed that the reaction time of the left MTLE patients was significantly longer than that of controls on the AJ task ( t = −3.396, P < 0.05). The left MTLE patients also exhibited diffusively decreased activation in the AJ task. Right hemisphere dominance of Broca's and Wernicke's areas was demonstrated in left MTLE patients. Conclusions Long-term activation of spikes in left MTLE patients results in language impairment, which is associated with an abnormality of the brain neural network.

Evaluation of fiber bundles across subjects through brain mapping and registration of diffusion tensor data

This paper presents a visualization and analysis framework for evaluating changes in structural organization of fiber bundles in human brain white matter. Statistical analysis of fiber bundle organization is conducted using an anisotropy measure, volume ratio (VR), which is ratio of anisotropic and isotropic components. Initially fiber bundles are tracked using a probabilistic algorithm starting from seed voxels. To ensure accurate selection of seed voxels and to prevent operator bias, a reference brain (MNI_152) is used when marking ROIs. Individual structural MRI brain scans are mapped to the reference using volumetric conformal parameterization. This mapping preserves topology and aligns features perfectly making it a robust and accurate registration technique. One-to-one mapping to the template allows ROI selection and subsequent transfer of ROI to structural MRI of subject. Affine registration coregisters structural MRI and DTI. Seed voxels are mapped to DTI using the resulting transformation parameters. To evaluate the proposed approach, MRI and DTI of 12 normal volunteers and 15 medial temporal lobe epilepsy patients are used. First, a statistical hypothesis testing is conducted to test for anisotropy changes in cingulum and fornix fiber bundles of epileptic patients. Experimental results reveal a 40% decrease in anisotropy levels of cingulum in patients compared to volunteers. They also show a 25% overall decrease in anisotropy of fornix. Secondly, shapes of the bundles are visualized in 3D illustrating that the bundles of epileptic patients are bumpy while those of normal volunteers are smooth.

Hippocampal removal affects visual but not auditory naming.

Dominant, left anteromedial temporal lobe resection (AMTLR) for seizure control carries risks to verbal episodic memory and visual object naming. Consistent with traditional thinking, verbal memory decline is considered a consequence of hippocampal removal and naming decline has been attributed to lateral temporal resection. Interestingly, recent findings suggest a potential relation between visual naming and hippocampal integrity, which is consistent with studies that link the hippocampus with higher level visual processing. Historically, naming has been evaluated using visual object naming tasks; however, naming can also be assessed using auditory verbal descriptions. Recent cortical stimulation studies have shown a neuroanatomic distinction between visual naming and auditory description naming. We speculated that unlike visual naming, the hippocampus is not involved in auditory naming, and hypothesized that left AMTLR would not result in auditory naming decline, despite visual naming and verbal memory decline. In this cohort study, we tested auditory naming, visual naming, and verbal memory in 25 left medial temporal lobe epilepsy (MTLE) and 20 right MTLE patients pre-AMTLR and 1 year post-AMTLR. Left AMTLR patients declined in visual naming and verbal memory, with no decline in auditory naming. Right AMTLR patients exhibited no decline. Results suggest that left anteromedial temporal lobe resection presents a greater risk to visual naming than auditory naming in patients with left medial temporal lobe epilepsy.

Facial emotion recognition impairment in chronic temporal lobe epilepsy

To evaluate facial emotion recognition (FER) in a cohort of 176 patients with chronic temporal lobe epilepsy (TLE). FER was tested by matching facial expressions with the verbal labels for the following basic emotions: happiness, sadness, fear, disgust, and anger. Emotion recognition performances were analyzed in medial (n = 140) and lateral (n = 36) TLE groups. Fifty healthy subjects served as controls. The clinical and neuroradiologic variables potentially affecting the ability to recognize facial expressions were taken into account. The medial TLE (MTLE) group showed impaired FER (86% correct recognition) compared to both the lateral TLE patients (FER = 93.5%) and the controls (FER = 96.4%), with 42% of MTLE patients recording rates of FER that were lower [by at least 2 standard deviations (SDs)] than the control mean. The MTLE group was impaired compared to the healthy controls in the recognition of all basic facial expressions except happiness. The patients with bilateral MTLE were the most severely impaired, followed by the right and then the left MTLE patients. FER was not affected by type of lesion, number of antiepileptic drugs (AEDs), aura semiology, or gender. Conversely, the early onset of seizures/epilepsy was related to FER deficits. These deficits were already established in young adulthood, with no evidence of progression in older MTLE patients. These results on a large cohort of TLE patients demonstrate that emotion recognition deficits are common in MTLE patients and widespread across negative emotions. We confirm that early onset seizures with right or bilateral medial temporal dysfunction lead to severe deficits in recognizing facial expressions of emotions.

Adaptive visual memory reorganization in right medial temporal lobe epilepsy

We investigated functional reorganization mechanisms of the human medial temporal lobe (MTL) for episodic memory, in patients suffering from medial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS). We used functional magnetic resonance imaging (fMRI) to measure brain activity changes during matched episodic encoding tasks of abstract words (Verbal) and line drawings (Visual), in patients with unilateral right MTLE undergoing presurgical evaluation and healthy controls. As expected, a significant interaction between material type and the side of MTL activity was present in the control group, with preferential involvement of the left hippocampus in verbal encoding and the right parahippocampal region in visual encoding. When compared with controls, right MTLE patients with intact performance activated a region in the left hippocampus more during visual encoding, which resulted in an interaction between group and hemisphere. Importantly, an effect of memory performance on visual encoding activity was observed in the patients, with greater engagement of the left MTL being associated with higher recognition scores. Interestingly, activity in the left MTL also depended on the epileptic seizure frequency, suggesting a role for this clinical parameter in the recruitment of contralateral regions. Taken together, these results indicate functional reorganization of the MTLs in right HS, through transfer of function from the right to the left hemisphere, and strongly suggest an adaptive role for such reorganization mechanism in supporting preserved visual memory.

Decreased basal fMRI functional connectivity in epileptogenic networks and contralateral compensatory mechanisms

A better understanding of interstructure relationship sustaining drug-resistant epileptogenic networks is crucial for surgical perspective and to better understand the consequences of epileptic processes on cognitive functions. We used resting-state fMRI to study basal functional connectivity within temporal lobes in medial temporal lobe epilepsy (MTLE) during interictal period. Two hundred consecutive single-shot GE-EPI acquisitions were acquired in 37 right-handed subjects (26 controls, eight patients presenting with left and three patients with right MTLE). For each hemisphere, normalized correlation coefficients were computed between pairs of time-course signals extracted from five regions involved in MTLE epileptogenic networks (Brodmann area 38, amygdala, entorhinal cortex (EC), anterior hippocampus (AntHip), and posterior hippocampus (PostHip)). In controls, an asymmetry was present with a global higher connectivity in the left temporal lobe. Relative to controls, the left MTLE group showed disruption of the left EC-AntHip link, and a trend of decreased connectivity of the left AntHip-PostHip link. In contrast, a trend of increased connectivity of the right AntHip-PostHip link was observed and was positively correlated to memory performance. At the individual level, seven out of the eight left MTLE patients showed decreased or disrupted functional connectivity. In this group, four patients with left TLE showed increased basal functional connectivity restricted to the right temporal lobe spared by seizures onset. A reverse pattern was observed at the individual level for patients with right TLE. This is the first demonstration of decreased basal functional connectivity within epileptogenic networks with concomitant contralateral increased connectivity possibly reflecting compensatory mechanisms.

Lateralization of hippocampal activation differs between left and right temporal lobe epilepsy patients and correlates with postsurgical verbal learning decrement

We addressed the question whether lateralization of memory-related medial temporal lobe (MTL) activity in medial temporal lobe epilepsy (MTLE) patients is determined by pathology or sex, differentiating between two MTL subregions implicated in visuospatial memory as regions-of-interest (ROI) - the hippocampus (Hc) and the parahippocampal place area (PPA). We further assessed the relation between lateralization of hippocampal activation and postsurgical memory decline regarding performance in standardized neuropsychological tests of verbal and visuospatial learning. Functional magnetic resonance imaging (fMRI) data were acquired from unilateral MTLE patients performing an object location memory task in a virtual environment. Individual lateralization indices (LI) based on memory-related brain activation patterns were calculated for each subject and ROI. Correlational analyses were computed between pre- to postsurgical changes in learning and asymmetry in hippocampal activation. Results revealed that lateralization of hippocampal, memory-related activity in patients with MTLE was determined by the side of seizure focus, not sex. Laterality of activation in the PPA was neither influenced by side of pathology nor sex. Lateralization of hippocampal activation was significantly correlated with decline in verbal learning after surgery. We were able to demonstrate that asymmetry of hippocampal fMRI-activation in unilateral MTLE patients is determined by the side of seizure focus, thus indicating the relative functional integrity of the hippocampi. This is corroborated by the finding that greater activation of the to-be-resected hippocampus leads to stronger verbal memory decline after surgery.

Trans-Sylvian selective amygdalohippocampectomy for medically intractable temporal lobe epilepsy: a single-centre experience

Selective amygdalohippocampectomy (SelAH) is now widely used in the surgical treatment of patients with medically intractable medial temporal lobe epilepsy (MTLE). We present our single-centre experience of a uniform series of drug-resistant MTLE patients treated exclusively with SelAH. A retrospective study of 50 adult patients (25 males, 25 females, mean age 34 years) suffering from medically intractable MTLE was conducted. All patients has been investigated under the same protocol and operated by SelAH performed by one surgeon. Immediate and long-term follow-up was also available and is presented. Forty-two patients (84%) became seizure free (Engel's I); eight of them (16%) were classified as Engel's II; four (8%) as Engel's III; and one as Engel's IV (2%). In 42 of them the final result has been achieved after a single operation, while in the rest eight after a second or third surgical procedure. The mean follow-up period was 6.2 years. Two permanent complications (4%) with no treatment-related mortality have been detected. SelAH performed in well selected cases, where concordance between electrophysiological and MR findings exists, can be a safe and effective surgical treatment method for medically intractable MTLE.

Does Resection of the Medial Temporal Lobe Improve the Outcome of Temporal Lobe Epilepsy Surgery?

Surgical removal of the hippocampus is the standard of care of patients with drug-resistant medial temporal lobe epilepsy (MTLE). The procedure carries a success rate of approximately 75%, but the reasons that some patients fail to achieve seizure control after surgery remain inexplicable. The question of whether the resection of medial temporal lobe structures in addition to the hippocampus would influence the surgical outcome in patients with MTLE was examined. We conducted voxel-based statistical analyses of postoperative high-resolution MRI of MTLE patients who underwent anteromedial temporal resection. We applied a cost function transformation of the resection maps for each patient to a common set of spatial coordinates, and we analyzed the contribution of histologically distinct segments of the medial temporal lobe cortex to the surgical outcome. We also performed a voxel-wise mapping of surgical outcome to the temporal lobe. We observed that the extent of hippocampal removal was associated with better outcomes. However, when the resection of the hippocampus was combined with the resection of the medial temporal lobe, specifically the entorhinal cortex, a greater likelihood of higher seizure control after surgery was found. Based on this finding, it is possible that the efficiency of the surgical treatment of MTLE can be improved by adjusting the procedure to include the resection of the entorhinal cortex, in addition to the resection of the hippocampus.

Postoperative Recovery of Hippocampal Contralateral Diffusivity in Medial Temporal Lobe Epilepsy

To search for a recovery after surgery of mean diffusivity (MD) values in the contralateral nonsclerotic hippocampus of patients with medial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS). Twenty-four MTLE patients (12 right-sided and 12 left-sided MTLE) and 36 healthy volunteers were investigated using diffusion tensor imaging. A region-of-interest approach was used to measure pre- and postoperative interictal hippocampal MD values in patients. Diffusion abnormalities in contralateral nonsclerotic hippocampus recovered after surgery (p<0.0001). A subgroup of 14 patients exhibited a clear increase in MD values whereas the remaining 10 patients were stable. No significant difference was found between the two subgroups for each of the electroclinical data studied including early postoperative outcome, all patients being either seizure free or with rare persistent auras. This finding suggests that diffusion abnormalities in contralateral hippocampus may represent a functional mechanism linked to the active epileptic process.

T2‐Weighted and T2 Relaxometry Images in Patients with Medial Temporal Lobe Epilepsy

Quantification of increased T2-weighted MRI signal that is associated with hippocampal sclerosis (HS) can be performed through (1) mean of hippocampal signal in single-echo T2 MRI and (2) hippocampal T2 relaxometry. It is not clear whether these two techniques are equivalent. In this study, we compare the hippocampal signal, detected by single-echo T2 quantification and by T2 relaxometry, in patients with medial temporal lobe epilepsy (MTLE). We studied magnetic resonance images from 50 MTLE patients and 15 healthy subjects. We compared the quantification of a T2 signal from single echo images to T2 relaxometry, both obtained from a manually traced region of interest (ROI) in coronal slices involving the whole hippocampus. Repeated measures ANOVA was used to evaluate the differences in the distribution of the Z-scores from single-echo T2 quantification and T2 relaxometry within subjects. We observed a significant difference between the measurements obtained from single-echo T2 quantification and T2 relaxometry (P < .001). Measurements from head, body, and tail of the hippocampus were different (P=.04), with a significant interaction between anatomic location and type of measurement used (P= .008). Post hoc paired comparisons revealed that T2 relaxometry yielded greater Z-scores for the body (P= .002) and tail (P < .0001). For each subject with MTLE, T2 relaxometry was able to detect a higher signal in the body and tail of the hippocampus compared to single-echo T2. This is a possible indicator that T2 relaxometry is more sensitive in detecting T2 abnormalities within the body and tail of the hippocampus in patients with MTLE.

Memory performance during the intracarotid amobarbital procedure and neuropsychological assessment in medial temporal lobe epilepsy: The limits of material specificity

We investigated the relationship between material-specific memory performance elicited during the Wada test, or intracarotid amobarbital procedure (IAP), and classic neuropsychological assessment in 89 surgical candidates with refractory medial temporal lobe epilepsy (MTLE). The neuropsychological battery included measures of simple and complex verbal and visual memory, whereas the IAP material consisted of verbal and dually encodable stimuli. Neuropsychological testing revealed that reduced verbal memory performance was associated with left-sided MTLE, whereas visual memory tasks revealed no differences between patients with left-sided and right-sided MTLE. During IAP, memory performance was worse with the ipsilesional hemisphere, regardless of lesion side. Most importantly, performance on verbal memory tests was significantly, but moderately, correlated with left hemispheric IAP performance, indicating that memory tasks using verbal material are a valid marker of left hemispheric integrity in left language-dominant MTLE patients and significantly predict left hemispheric memory performance during IAP. In contrast, performance on classic visual memory tests is unrelated to right hemispheric IAP performance, suggesting that the currently used visual memory stimuli do not reflect right hemispheric sensitivity.

Clinico-electrical Characteristics of Lateral Temporal Lobe Epilepsy; Anterior and Posterior Lateral Temporal Lobe Epilepsy

Background and PurposeThis study aimed to determine whether there are clinicoelectrical differences between anterior lateral temporal lobe epilepsy (ALTLE) and posterior lateral temporal lobe epilepsy (PLTLE), taking medial temporal lobe epilepsy (MTLE) as a reference.MethodsWe analyzed the historical information, ictal semiologies, and ictal EEGs of temporal lobe epilepsy patients with a documented favorable surgical outcome (Engel class I or II) at follow-up after more than one year. LTLE was defined when a discrete lesion on MRI or an ictal onset zone in invasive study was located outside the collateral sulcus. LTLE was further divided into ALTLE and PLTLE by reference to the line across the cerebral peduncle. Total 107 seizures of 13 ALTLE, 8 PLTLE and 21 MTLE patients were reviewed.ResultsInitial hypomotor symptom was frequently observed in PLTLE (P<0.001). Oroalimentary automatism (OAA) was not observed initially in PLTLE. Generalized tonic-clonic seizures occurred significantly earlier in PLTLE than in ALTLE or MTLE (P< 0.001). Ictal scalp EEG was not helpful in differentiating between ALTLE and PLTLE.ConclusionsFrequent hypomotor onset, the absence of initial oroalimentary automatism, and early generalization are characteristic findings of PLTLE, although they are insufficient to differentiate it from ALTLE or MTLE.

Diffusion tensor imaging in medial temporal lobe epilepsy with hippocampal sclerosis

Interictal diffusion imaging studies in patients with medial temporal lobe epilepsy (MTLE) accompanied by hippocampal sclerosis (HS) have shown an increased diffusivity in the epileptogenic hippocampus. In this study, we wanted to explore the whole brain in order to determine if MTLE could have an impact on the organization and the architecture of a large cerebral network and to identify clinical factors that could mediate diffusion abnormalities. Diffusion tensor imaging (DTI) and statistical parametric mapping of the entire brain were performed in 35 well-defined MTLE patients and in 36 healthy volunteers. SPM analyses identified three abnormal areas: an increased diffusivity was detected in the epileptic hippocampus and the ipsilateral temporal structures associated with a decreased anisotropy along the temporal lobe, a decreased diffusivity was found in the contralateral non-sclerotic hippocampus, the amygdala, and the temporal pole, and finally, a decreased anisotropy was noted ipsilaterally in posterior extratemporal regions. Duration of epilepsy, age at onset, and the frequency of generalized tonic–clonic seizures or partial complex seizures did not correlate with the presence of diffusion abnormalities. Region of interest analysis in the hippocampus/parahippocampus demonstrated a correlation between lower ipsilateral diffusivity values and occurrence of epigastric aura and between higher anisotropy values in both hemispheres and history of febrile seizures. In conclusion, this study showed that diffusion abnormalities are not restricted to the pathologic hippocampus and involve a larger network. This pattern may indirectly reflect the epileptogenic network and may be interpreted as a cause or a consequence of epilepsy.

Epileptic activity influences the speech organization in medial temporal lobe epilepsy.

Factors influencing atypical speech lateralization have theoretical importance in understanding the organization and reorganization of higher cognitive functions, as well as having practical implications, especially in brain surgery and neurorehabilitation. Atypical (right-sided or bilateral) language representation is more frequent in focal epilepsy than in healthy people. This difference is thought to be related to early childhood brain injuries localized in the neighbourhood of speech centres. The effect of epileptic activity on speech lateralization has not been investigated, although much data suggest that epileptic activity may interfere with higher brain functions. It can only be evaluated in a homogeneous human population with epilepsy having the same lesion type in the same localization. For these reasons, we investigated 184 patients with medial temporal lobe epilepsy (MTLE) due to unilateral hippocampal sclerosis (HS), but without other epileptogenic lesions. All patients underwent comprehensive presurgical evaluation. In MTLE, the influence of age at the time of brain damage, i.e. the initial precipitating injury (IPI), could be evaluated separately from the other timing factors. Of 100 patients in whom a Wada test was performed, left-sided speech occurred in 76% of the left-sided and in 100% of the right-sided MTLE patients (P < 0.05). For further evaluation, we included only the 83 left-sided MTLE patients. The mean age at seizure onset was 10.1 +/- 7.8 years (range 1-37 years); the mean age at evaluation was 35.7 +/- 9.8 years. Based on the Wada test, left-sided speech was present in 63 patients, while in 20 (24%) patients the Wada test revealed atypical speech dominance. We found that atypical speech representation in left MTLE was associated with higher spiking frequency (P < 0.05) and with sensory auras representing an ictal involvement of the lateral temporal structures (P < 0.01). Psychic auras suggesting limbic seizure spread showed a significant association with left-sided speech dominance in left MTLE (P < 0.05). Neither age at epilepsy onset, nor age at IPI was associated with atypical speech in left MTLE. Conclusively, we found that in patients with focal epilepsy, not only the known factors, i.e. the age at which the brain injury occurred and its localization, but also the epileptic activity itself, i.e. interictal discharges and seizure spread, may influence speech reorganization. Our findings also suggest that not only structural elements but also functional factors have an effect on the language organization of the brain.

Clinical features and surgical outcome of medial temporal lobe epilepsy with a history of complex febrile convulsions

Purpose: Temporal lobe epilepsy (TLE) is frequently associated with hippocampal sclerosis (HS) and complex febrile convulsions (CFC). The causal relationship between TLE, HS, and CFC is unclear. There is also contradictory data whether CFC-associated TLE is a distinct epilepsy syndrome and has different surgical outcome than other medial TLEs. Methods: We investigated 133 patients (aged 16–59 years) with HS-associated TLE. Thirty-six patients with CFC (CFC group) versus 97 patients without febrile convulsions (NFC group) were compared for clinical history, video-EEG recorded seizure semiology, and surgical outcome. Results: In the CFC group the right-sided HS (67% versus 32%) occurred more frequently than in the NFC group ( P<0.001). The two groups did not differ according to the clinical features, both groups share the typical symptoms and findings of the medial TLE. In the CFC group, seizure-freedom 2 years after surgery was 91%, while in the NFC group it was only 64% ( P=0.023). This difference was significant even after considering the other known predictive factors for medial TLE. Conclusions: Medial TLE with CFC is not a distinct epilepsy syndrome. The surgical outcome, however, is much more favorable in these patients in comparison with medial TLE patients who had no history of febrile convulsions.

Alteration of functional neuroanatomy of simple object memory in medial temporal lobe epilepsy patients.

Using H2 15O PET, we examined the neuroanatomy associated with a simple form of episodic memory in patients with right or left medial temporal lobe epilepsy and normal healthy controls. When line drawings of common objects were memorized and tested after a 30 min delay, no behavioral difference was found between the patient groups and the controls. However, the patients with epilepsy showed greater cortical activations than the control group on the side ipsilateral to the epileptic focus. rCBF in the anterior thalamic region was enhanced in patients relative to the control group. The results showed that long-term dysfunction of the medial temporal lobe might reinforce alternative memory pathways and recruit a distributed cortical network ipsilateral to their epilepsy focus.

Independent component analysis of ictal EEG in medial temporal lobe epilepsy.

Application of independent component analysis (ICA) to interictal EEGs and to event-related potentials has helped noise reduction and source localization. However, ICA has not been used for the analysis of ictal EEGs in partial seizures. In this study, we applied ICA to the ictal EEGs of patients with medial temporal lobe epilepsy (TLE) and investigated whether ictal components can be separated and whether they indicate correct lateralization. Twenty-four EEGs from medial TLE patients were analyzed with the extended ICA algorithm. Among the resultant 20 components in each EEG, we selected components with an ictal nature and reviewed their corresponding topographic maps for the lateralization. We then applied quantitative methods for the verification of increased quality of the reconstructed EEGs. All ictal EEGs were successfully decomposed into one or more ictal components and nonictal components. After EEG reconstruction with exclusion of artifacts, the lateralizing power of the ictal EEG was increased from 75 to 96%. ICA can separate successfully the manifold components of ictal rhythms and can improve EEG quality.

Episodic memory in left temporal lobe epilepsy: a functional MRI study.

Left medial temporal lobe epilepsy (MTLE) is associated with verbal memory impairment usually related to hippocampal damage. We used functional MRI (fMRI) to investigate the patterns of functional activity in healthy volunteers and MTLE patients engaged in verbal episodic memory tasks to look for evidence of a reallocation of verbal memory in epileptic patients. fMRI data were collected from seven MTLE patients with left-sided hippocampal sclerosis and 10 healthy right-handed control subjects on a 3T scanner. Subjects were instructed to learn a list of 17 words (encoding) and then to recall them (retrieval) on successive trials. Healthy volunteers and patients both exhibited bilateral activation (right higher than left) of the parahippocampal gyrus during the retrieval. This effect was more marked in the control subjects. In contrast to the control subjects, patients exhibited consistent and extensive left prefrontal activations in all the memory tasks. These findings show that verbal memory tasks did not involve the same functional patterns in patients and healthy volunteers. This may be interpreted as a dysfunctional response due to the epilepsy and left hippocampal sclerosis, and could reflect the early onset and progressive course of the disease.