Functional substrate for memory function differences between patients with left and right mesial temporal lobe epilepsy associated with hippocampal sclerosis

ObjectiveLittle is known about the functional substrate for memory function differences in patients with left or right mesial temporal lobe epilepsy (mTLE) associated with hippocampal sclerosis (HS) from an electrophysiological perspective. To characterize these differences, we hypothesized that hippocampal theta connectivity in the resting-state might be different between patients with left and right mTLE with HS and be correlated with memory performance.MethodsResting-state hippocampal theta connectivity, identified via whole-brain magnetoencephalography, was evaluated. Connectivity and memory function in 41 patients with mTLE with HS (left mTLE = 22; right mTLE = 19) were compared with those in 46 age-matched healthy controls and 28 patients with focal cortical dysplasia (FCD) but without HS.ResultsConnectivity between the right hippocampus and the left middle frontal gyrus was significantly stronger in patients with right mTLE than in patients with left mTLE. Moreover, this connectivity was positively correlated with delayed verbal recall and recognition scores in patients with mTLE. Patients with left mTLE had greater delayed recall impairment than patients with right mTLE and FCD. Similarly, delayed recognition performance was worse in patients with left mTLE than in patients with right mTLE and FCD. No significant differences in memory function between patients with right mTLE and FCD were detected. Patients with right mTLE showed significantly stronger hippocampal theta connectivity between the right hippocampus and left middle frontal gyrus than patients with FCD and left mTLE.ConclusionOur results suggest that right hippocampal–left middle frontal theta connectivity could be a functional substrate that can account for differences in memory function between patients with left and right mTLE. This functional substrate might be related to different compensatory mechanisms against the structural hippocampal lesions in left and right mTLE groups. Given the positive correlation between connectivity and delayed verbal memory function, hemispheric-specific hippocampal–frontal theta connectivity assessment could be useful as an electrophysiological indicator of delayed verbal memory function in patients with mTLE with HS.     

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.     

Impact of hippocampal subfield histopathology in episodic memory impairment in mesial temporal lobe epilepsy and hippocampal sclerosis

ObjectiveThe objective of the study was to analyze preoperative visual and verbal episodic memories in a homogeneous series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) submitted to corticoamygdalohippocampectomy and its association with neuronal cell density of each hippocampal subfield.MethodsThe hippocampi of 72 right-handed patients were collected and prepared for histopathological examination. Hippocampal sclerosis patterns were determined, and neuronal cell density was calculated. Preoperatively, two verbal and two visual memory tests (immediate and delayed recalls) were applied, and patients were divided into two groups, left and right MTLE (36/36).ResultsThere were no statistical differences between groups regarding demographic and clinical data. Cornu Ammonis 4 (CA4) neuronal density was significantly lower in the right hippocampus compared with the left (p = 0.048). The groups with HS presented different memory performance — the right HS were worse in visual memory test [Complex Rey Figure, immediate (p = 0.001) and delayed (p = 0.009)], but better in one verbal task [RAVLT delayed (p = 0.005)]. Multiple regression analysis suggested that the verbal memory performance of the group with left HS was explained by CA1 neuronal density since both tasks were significantly influenced by CA1 [Logical Memory immediate recall (p = 0.050) and Logical Memory and RAVLT delayed recalls (p = 0.004 and p = 0.001, respectively)]. For patients with right HS, both CA1 subfield integrity (p = 0.006) and epilepsy duration (p = 0.012) explained Complex Rey Figure immediate recall performance. Ultimately, epilepsy duration also explained the performance in the Complex Rey Figure delayed recall (p < 0.001).SignificanceCornu Ammonis 1 (CA1) hippocampal subfield was related to immediate and delayed recalls of verbal memory tests in left HS, while CA1 and epilepsy duration were associated with visual memory performance in patients with right HS.     

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.     

Drug-resistant temporal lobe epilepsy due to middle fossa meningoencephalocele in a child: A surgical case report

BackgroundMeningoencephalocele (ME) of the temporal lobe through a bone defect in the middle cranial fossa is a rare known cause of refractory temporal lobe epilepsy (TLE). ME-induced drug-resistant TLE has been described in adults; however, its incidence in children is very rare.Case reportA 7-year-old girl presented at our hospital with brief episodes of impaired consciousness and enuresis. Initial brain MRI results were interpreted as normal. Her seizures could not be controlled even with multiple anti-seizure medications. She was diagnosed with drug-resistant TLE, which presented with prolonged impaired awareness seizures for 30–60 s and secondary bilateral tonic seizures. At 9 years of age, brain MRI revealed a left temporal anteroinferior ME with a congenital bone defect in the left middle cranial fossa. She was referred for presurgical epilepsy evaluation. Long-term video electroencephalography (EEG) failed to reveal regional abnormality in the left temporal lobe; invasive evaluation using stereoelectroencephalography (SEEG) was thus indicated.Ictal onset SEEG was identified in the temporal pole near the ME which was rapidly propagated to the mesial temporal structures and other cortical regions. The left temporal pole including the ME was micro-surgically disconnected while preserving the hippocampus and amygdala. The patient’s seizures have been completely controlled for 1 year and 6 months post-operatively.ConclusionSEEG revealed rapid propagation of ictal activity in this patient’s case, confirming that the ME was epileptogenic. Since the majority of patients with refractory epilepsy caused by ME have favorable postoperative seizure outcomes, it is important to carefully check for ME in drug-resistant TLE patients with apparently normal MRI.     

Long-term postoperative atrophy of contralateral hippocampus and cognitive function in unilateral refractory MTLE with unilateral hippocampal sclerosis

ObjectiveThis study aimed to evaluate long-term atrophy in contralateral hippocampal volume after surgery for unilateral MTLE, as well as the cognitive outcome for patients submitted to either selective transsylvian amygdalohippocampectomy (SelAH) or anterior temporal lobe resection (ATL).MethodsWe performed a longitudinal study of 47 patients with MRI signs of unilateral hippocampal sclerosis (23 patients with right-sided hippocampal sclerosis) who underwent surgical treatment for MTLE. They underwent preoperative/postoperative high-resolution MRI as well as neuropsychological assessment for memory and estimated IQ. To investigate possible changes in the contralateral hippocampus of patients, we included 28 controls who underwent two MRIs at long-term intervals.ResultsThe volumetry using preoperative MRI showed significant hippocampal atrophy ipsilateral to the side of surgery when compared with controls (p < 0.0001) but no differences in contralateral hippocampal volumes. The mean postoperative follow-up was 8.7 years (± 2.5 SD; median = 8.0). Our patients were classified as Engel I (80%), Engel II (18.2%), and Engel III (1.8%). We observed a small but significant reduction in the contralateral hippocampus of patients but no volume changes in controls. Most of the patients presented small declines in both estimated IQ and memory, which were more pronounced in patients with left TLE and in those with persistent seizures. Different surgical approaches did not impose differences in seizure control or in cognitive outcome.ConclusionsWe observed small declines in cognitive scores with most of these patients, which were worse in patients with left-sided resection and in those who continued to suffer from postoperative seizures. We also demonstrated that manual volumetry can reveal a reduction in volume in the contralateral hippocampus, although this change was mild and could not be detected by visual analysis. These new findings suggest that dynamic processes continue to act after the removal of the hippocampus, and further studies with larger groups may help in understanding the underlying mechanisms.     

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.     

Mesio-temporal ictal semiology as an indicator for surgical treatment of epilepsies with large multilobar cerebral lesions

PurposeMesio-temporal ictal semiology is sometimes observed in patients with large multilobar lesion. In this situation, surgery is often discarded because of the lesion size and/or suspicion of extended or multifocal epileptogenic areas. In this retrospective study we evaluated the surgical outcome of such patients in order to assess whether the electro-clinical presentation of seizures could be a prognostic marker of surgical outcome.MethodsAmong the temporal lobe epilepsy population explored in our department between 2000 and 2011 (240 patients), we identified 7 patients who presented an extensive lesion on brain Magnetic Resonance Imaging (MRI) (multilobar in four, hemispheric in two, and bilateral in one). All patients underwent ¹⁸Fluorodeoxyglucose Positron Emission Tomography, which showed large, hemispheric or multilobar, areas of glucose hypometabolism. Because of the large lesion size, all patients were explored by stereoelectroencephalography (SEEG) before taking a decision regarding surgical indication.ResultsSEEG confirmed the temporal origin of the seizures and discarded the possibility of multiple epileptogenic zones. A temporal lobectomy, tailored on the basis of SEEG data, was proposed to the seven patients. The seven patients are classified Engel class I after the surgery (mean follow-up: 37.4 ± 22.1 months).ConclusionOur data thus suggest that, even in the absence of hippocampal MRI abnormality, ictal symptoms compatible with a temporal origin of seizures should be considered as a reliable indicator for surgery eligibility regardless of MRI lesion size. On the basis of our findings, the mesio-temporal semiology of seizures appears as one of the most reliable markers of operability in patients with large MRI lesions. These patients should not be excluded a priori from invasive exploration and surgical treatment, even if a large portion of their lesion is likely to be left in place after surgery.     

Diffusion tractography of the fornix in schizophrenia

BackgroundWhite matter fiber tracts, especially those interconnecting the frontal and temporal lobes, are likely implicated in pathophysiology of schizophrenia. Very few studies, however, have focused on the fornix, a compact bundle of white matter fibers, projecting from the hippocampus to the septum, anterior nucleus of the thalamus and the mamillary bodies. Diffusion Tensor Imaging (DTI), and a new post-processing method, fiber tractography, provides a unique opportunity to visualize and to quantify entire trajectories of fiber bundles, such as the fornix, in vivo. We applied these techniques to quantify fornix diffusion anisotropy in schizophrenia.MethodsDTI images were used to evaluate the left and the right fornix in 36 male patients diagnosed with chronic schizophrenia and 35 male healthy individuals, group matched on age, parental socioeconomic status, and handedness. Regions of interest were drawn manually, blind to group membership, to guide tractography, and fractional anisotropy (FA), a measure of fiber integrity, was calculated and averaged over the entire tract for each subject. The Doors and People test (DPT) was used to evaluate visual and verbal memory, combined recall and combined recognition.ResultsAnalysis of variance was performed and findings demonstrated a difference between patients with schizophrenia and controls for fornix FA (p = 0.006). Protected post-hoc independent sample t-tests demonstrated a bilateral FA decrease in schizophrenia, compared with control subjects (left side: p = 0.048; right side p = 0.006). Higher fornix FA was statistically significantly correlated with DPT and measures of combined visual memory (r = 0.554, p = 0.026), combined verbal memory (r = 0.647, p = 0.007), combined recall (r = 0.516, p = 0.041), and combined recognition (r = 0.710, p = 0.002) for the control group. No such statistically significant correlations were found in the patient group.ConclusionsOur findings show the utility of applying DTI and tractography to study white matter fiber tracts in vivo in schizophrenia. Specifically, we observed a bilateral disruption in fornix integrity in schizophrenia, thus broadening our understanding of the pathophysiology of this disease.     

Increased hippocampal head diffusivity predicts impaired episodic memory performance in early Alzheimer's disease

Recent neuroanatomical and functional neuroimaging studies indicate that the anterior part of the hippocampus, rather than the whole structure, may be specifically involved in episodic memory. In the present work, we examined whether anterior structural measurements are superior to other regional or global measurements in mapping functionally relevant degenerative alterations of the hippocampus in Alzheimer's disease (AD).Twenty patients with early AD (MMSE 25.7 ± 1.7) and 18 healthy controls were studied using magnetic resonance and diffusion-tensor imaging. Using a regions-of-interest analysis, we obtained volumetric and diffusivity measures of the hippocampal head and body-tail-section as well as of the whole hippocampus. Detailed cognitive evaluation was based on the CERAD battery.All volumetric measures as well as diffusivity of the hippocampus head were significantly (p < 0.01) altered in patients as compared to controls. In patients, increased left head diffusivity significantly (p < 0.01) correlated with performance on free delayed verbal recall test (DVR) (r = −0.74, p = 0.0002) and with the CERAD global score. Reduced volume of the left body-tail was also associated with performance on DVR (r = 0.62, p = 0.004). Stepwise regression analyses revealed that increased left head diffusivity was the only predictor for performance on DVR (R² = 52%, p < 0.0005).These findings suggest that anterior hippocampus diffusivity is more closely related to verbal episodic memory impairment than other regional or global structural measures. Our data support the hypothesis of functional differentiation in general and the specific role of the anterior hippocampus in episodic memory in particular. Diffusivity measurements might be highly sensitive to functionally relevant degenerative alterations of the hippocampus.     

Insular and insulo-opercular epilepsy in childhood: An SEEG study

PurposeIn recent years, there have been series analysing the electro-clinical correlations of insular epilepsy in adult populations. In contrast, the ictal semiology in children with insular epilepsy is poorly described. Considering that early and successful surgery may greatly improve the cognitive outcome and quality of life, it is worthwhile to deepen our knowledge of insular epilepsy in children.MethodsWe retrospectively evaluated ten children with drug-resistant focal insular epilepsy who had been consecutively explored with stereoelectroencephalography (SEEG), followed by individually tailored resective surgery that included part of the insula in all cases. A detailed anatomo-electro-clinical analysis of non-invasive EEG and SEEG data was performed. At least one of the electrodes explored the insular cortex. SEEG analysis confirmed that the insular cortex was included in the ictal onset zone.ResultsEpilepsy onset was mostly during the first year of life, characterized by subtle seizures as well as spasms and myoclonic seizures. Later on, neurovegetative signs and asymmetric tonic and hypermotor seizures (HMS) dominated the ictal semiology. The epileptogenic zone was frequently wider than insular with frontal and central predominance. In eight patients, the tailored resection included a lesion. In seven patients, an Engel class 1 outcome as well as neuropsychological and behavioural improvement was obtained.ConclusionsSEEG is feasible and useful in children with drug-resistant insular epilepsy which is often characterized by autonomic symptoms as the initial symptoms and should be suspected in cases with HMS, asymmetric tonic seizures and even asymmetric spasms. Early propagation is mostly frontal and central. Analysis of a larger population is required to refine these findings.     

Multiple hippocampal transections for intractable hippocampal epilepsy: Seizure outcome

PurposeThe purpose of this study was to evaluate the seizure outcomes after transverse multiple hippocampal transections (MHTs) in 13 patients with intractable TLE.MethodsThirteen patients with normal memory scores, including 8 with nonlesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. After confirming hippocampal seizure onset, they underwent MHT. Intraoperative monitoring was done with 5–6 hippocampal electrodes spaced at approximately 1-cm intervals and spike counting for 5–8 min before each cut. The number of transections ranged between 4 and 7. Neuropsychological assessment was completed preoperatively and postoperatively for all patients and will be reported separately.ResultsDuration of epilepsy ranged between 5 and 55 years. There were no complications. Intraoperatively, MHT resulted in marked spike reduction (p = 0.003, paired t-test). Ten patients (77%) are seizure-free (average follow-up was 33 months, range 20–65 months) without medication changes. One of the 3 patients with persistent seizures had an MRI revealing incomplete transections, another had an additional neocortical seizure focus (as suggested by pure aphasic seizures), and the third had only 2 seizures in 4 years, one of which occurred during antiseizure medication withdrawal. Verbal and visual memory outcomes will be reported separately. Right and left hippocampal volumes were not different preoperatively (n = 12, p = 0.64, Wilcoxon signed-rank test), but the transected hippocampal volume decreased postoperatively (p = 0.0173).ConclusionsMultiple hippocampal transections provide an effective intervention and a safe alternative to temporal lobectomy in patients with hippocampal epilepsy.     

Does the Co-occurrence of FGFR3 Gene Mutation in Hypochondroplasia,Medial Temporal Lobe Dysgenesis,and Focal Epilepsy Suggest a Syndrome?

BackgroundHypochondroplasia is a rare skeletal dysplasia characterized by disproportionately short stature, lumbar lordosis, and limited extension of the elbow caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene that plays a role in controlling nervous system development. Hypochondroplasia with FGFR3 mutation associated with bilateral medial temporal lobe anomalies and focal epilepsy was previously reported in several patients.PatientWe report clinical, electroclinical, and neuroradiological findings of one patient affected by hypochondroplasia.ResultsClinical diagnosis was confirmed by molecular analysis of the FGFR3 gene, which showed a N540 K mutation. The patient had normal psychomotor development and showed early-onset focal seizures with left temporal localization on interictal and ictal electroencephalograph. The seizures were well controlled, and the patient has been seizure-free since infancy. Magnetic resonance imaging showed abnormal anteriorly posteriorly infolding in the hippocampus and abnormally oriented parahippocampus sulci, and additional cortical rim dysplasia with gray-white matter junction blurring in the hippocampus.ConclusionsThe present case of hypochondroplasia and FGFR3 mutation in Asn540Lys associated with characteristic abnormalities involving bilaterally medial temporal lobe structures, probable hippocampal cortex focal dysplasia, and early onset of focal epilepsy underscores the possibility of a rare syndrome.     

Theory of mind in obsessive-compulsive disorder: Comparison with healthy controls

AimTheory of mind (ToM) is the ability to represent one's own or another's mental states and has been found to be impaired in many psychiatric disorders. Our objective was to compare ToM abilities of patients with obsessive-compulsive disorder (OCD) with healthy controls and to investigate the relation between some illness features, other cognitive functions and ToM abilities of patients.MethodThirty OCD patients and age, sex and education matched 30 healthy controls were compared according to their performances on ToM tasks (including first and second order false belief, hinting task and double-bluff task), verbal memory processes test, Weschler memory test (WMT) (logical memory, visual reproduction and digit span sub-tests), stroop test.ResultsPatients’ performances were worse than healthy controls on all of the ToM tasks, but the results were significant for only for double-bluff task (t = ?3.992, df = 36.157, p < 0.01). Performance on double-bluff task was significantly and positively correlated with visual reproduction-immediate recall (r = ?0.411, p < 0.05) and visual reproduction-delayed recall (r = 0.478, p < 0.05), hinting task was significantly and positively correlated with verbal memory (r = 0.481, p < 0.05).ConclusionThese results show “basic” ToM abilities of OCD patients are generally preserved, but they show significant reduction in their “advanced” ToM abilities, which seem to be related to their reduced memory capacities. The possible reasons for the relation between memory and ToM impairments, as well as the clinical significance of ToM deficits in OCD are discussed.     

Computerized Cognitive Testing in Epilepsy (CCTE): A new method for cognitive screening

PurposeOptimized therapy in epilepsy should include individual care for cognitive functions. Here we introduce a computerized screening instrument, called “Computerized Cognitive Testing in Epilepsy” (CCTE), which allows for time-efficient repetitive assessment of the patient's cognitive profile regarding the domains of memory and attention, which are frequently impaired due to side effects of antiepileptic medication.MethodsThe CCTE battery takes 30 min and covers tasks of verbal and figural memory, cognitive speed, attention and working memory. The patient's results are displayed immediately in comparison to age-related normative data. For evaluation of psychometrics and clinical correlations, data from patients of a tertiary referral epilepsy center (n = 240) and healthy subjects (n = 83) were explored.ResultsCCTE subtests show good reliability and concurrent validity compared to standard neuropsychological tests (p < 0.01). Adverse cognitive effects of antiepileptic medication can be detected (p < 0.05), e.g. significant negative effects of increasing drug load. Specific epilepsy subgroups, e.g. focal versus primary generalized epilepsy or right versus left mesial temporal lobe epilepsy, showed different CCTE profiles.ConclusionCCTE appears valuable for early detection of individual cognitive alterations related to medication. In addition, it displays interesting differences between epilepsy syndromes. The CCTE battery provides a standardized, time- and personnel-efficient assessment of cognitive functions open to a large number of patients and applicable for clinical and scientific use in epilepsy.     

Spontaneous ripples in the hippocampus correlate with epileptogenicity and not memory function in patients with refractory epilepsy

IntroductionHigh-frequency oscillations (HFOs, 80–500 Hz) are newly-described EEG markers of epileptogenicity. The proportion of physiological and pathological HFOs is unclear, as frequency analysis is insufficient for separating the two types of events. For instance, ripples (80–250 Hz) also occur physiologically during memory consolidation processes in medial temporal lobe structures. We investigated the correlation between HFO rates and memory performance.MethodsPatients investigated with bilateral medial temporal electrodes and an intellectual capacity allowing for memory testing were included. High-frequency oscillations were visually marked, and rates of HFOs were calculated for each channel during slow-wave sleep. Patients underwent three verbal and three nonverbal memory tests. They were grouped into severe impairment, some impairment, mostly intact, or intact for verbal and nonverbal memory. We calculated a Pearson correlation between HFO rates in the hippocampi and the memory category and compared HFO rates in each hippocampus with the corresponding (verbal — left, nonverbal — right) memory result using Wilcoxon rank-sum test.ResultsTwenty patients were included; ten had bilateral, five had unilateral, and five had no memory impairment. Unilateral memory impairment was verbal in one patient and nonverbal in four. There was no correlation between HFO rates and memory performance in seizure onset areas. There was, however, a significant negative correlation between the overall memory performance and ripple rates (r = − 0.50, p = 0.03) outside the seizure onset zone.ConclusionOur results suggest that the majority of spontaneous hippocampal ripples, as defined in the present study, may reflect pathological activity, taking into account the association with memory impairment. The absence of negative correlation between memory performance and HFO rates in seizure onset areas could be explained by HFO rates in the SOZ being generally so high that differences between areas with remaining and impaired memory function cannot be seen.     

Memory during subclinical hippocampal seizures

We performed neuropsychological testing in 2 patients during subclinical hippocampal seizures recorded with depth electrodes. Neither subject showed impairment of consciousness, orientation, motor skills, or verbal fluency. The rapidity of recall of a well-learned word list was impaired in 1 subject during ictal fast spiking in the left hippocampus. Subclinical seizure activity may be responsible for a portion of the memory deficits found in patients with epilepsy.     

Precision mapping of the epileptogenic network with low- and high-frequency stimulation of anterior nucleus of thalamus

ObjectiveThe goal of thalamic deep brain stimulation in epilepsy is to engage and modulate the epileptogenic network. We demonstrate how the anterior nucleus of thalamus (ANT) stimulation engages the epileptogenic network using electrophysiological measures (gamma response and post-stimulation excitability).MethodsFive patients with suspected temporal lobe epilepsy syndrome, undergoing stereo-electroencephalography (SEEG), were enrolled in the IRB approved study to undergo recording and stimulation of the ANT. We analyzed the extent of gamma-band response (activation or suppression) and post-stimulation change in excitability in various cortical regions during low (10 Hz) and high (50 Hz) frequency stimulations.Results10 Hz stimulation increased cortical gamma, whereas 50 Hz stimulation suppressed the gamma responses. The maximum response to stimuli was in the hippocampus. High epileptogenicity regions were more susceptible to stimulation. Both 10-and 50 Hz stimulations decreased post-stimulation cortical excitability. The greater the gamma-band activation with 10 Hz stimulation, the greater was the decrease in post-stimulation excitability.ConclusionsWe define an EEG marker that delineates stimulation-specific nodal engagement. We proved that nodes that were engaged with the thalamus during stimulation were more likely to show a short term decrease in post-stimulation excitability.SignificancePatient-specific engagement patterns during stimulation can be mapped with SEEG that can be used to optimize stimulation parameters.     

The “Connectivity Epileptogenicity Index ” (cEI), a method for mapping the different seizure onset patterns in StereoElectroEncephalography recorded seizures

ObjectiveLocalization of epileptogenic brain regions is a crucial aim of pre-surgical evaluation of patients with drug-resistant epilepsy. Several methods have been proposed to identify the seizure onset zone, particularly based on the detection of fast activity. Most of these methods are inefficient to detect slower patterns of onset that account for 20–30% of commonly observed Stereo-Electro-Encephalography (SEEG) patterns. We seek to evaluate the performance of a new quantified measure called the Connectivity Epileptogenicity Index (cEI) in various types of seizure onset patterns.MethodsWe studied SEEG recorded seizures from 51 patients, suffering from focal drug-resistant epilepsy. The cEI combines a directed connectivity measure (“out-degrees”) and the original epileptogenicity index (EI). Quantified results (Out-degrees, cEI and EI) were compared to visually defined seizure onset zone (vSOZ). We computed recall (sensitivity) and precision (proportion of correct detections within all detections) with vSOZ as a reference. The quality of the detector was quantified by the area under the precision-recall curve.ResultsBest results (in terms of match with vSOZ) were obtained for cEI. For seizures with fast onset patterns, cEI and EI gave comparable results. For seizures with slow onset patterns, cEI gave a better estimation of the vSOZ than EI.ConclusionsWe observed that cEI discloses better performance than EI when seizures starts with slower patterns and equal to EI in seizures with fast onset patterns.SignificanceThe cEI is a promising new tool for epileptologists, that helps characterizing the seizure onset zone in sEEG, in a robust way despite variations in seizure onset patterns.     

Activity of hippocampal,amygdala, and neocortex during the Rey auditory verbal learning test: An event-related potential study in epileptic patients

ObjectivePrevious evidence in epileptic subjects has shown that theta (about 4–7 Hz) and gamma rhythms (about 40–45 Hz) of hippocampus, amygdala, and neocortex were temporally synchronized during the listening of repeated words successfully remembered (Babiloni et al., 2009). Here we re-analyzed those electroencephalographic (EEG) data to test whether a parallel increase in amplitude of late positive event-related potentials takes place.MethodsIntracerebral electroencephalographic (EEG) activity had been recorded in five subjects with drug-resistant temporal lobe epilepsy, undergoing pre-surgical evaluation. During the recording of the intracerebral EEG activity, the subjects performed a computerized version of the Rey auditory verbal learning test (RAVLT). They heard the same list of 15 common words for five times. Each time, immediately after the listening of the list, the subjects were required to repeat as many words as they could recall.ResultsWe found that late positive event-related potentials (ERPs) peaking at about 350 ms post-stimulus in amygdala, hippocampus, and occipital–temporal cortex had a higher amplitude during the listening of the repeated words that were subsequently recalled than for those that were not recalled.ConclusionsLate positive ERPs reflect a functional mechanism implemented in a human brain network spanning amygdala, hippocampus, and occipital–temporal cortex which is at the basis of the memorization processes of verbal materials.SignificanceThis ERP component is a promising neuromarker of successful memorization of repeated words in humans.