A Learned Map for Places and Concepts in the Human Medial Temporal Lobe.

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL microwire recordings from 20 patients (9 female, 11 male) navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings. The array of local field potentials in the MTL contains sufficient information for above-chance decoding of subjects' instantaneous location in the environment. Closer examination revealed that as subjects gain experience with the environment the field potentials come to represent both the subjects' locations in virtual space and in high-dimensional semantic space. Similarly, we observe a learning effect on temporal sequence coding. Over time, field potentials come to represent future locations, even after controlling for spatial proximity. This predictive coding of future states, more so than the strength of spatial representations per se, is linked to variability in subjects' navigation performance. Our results thus support the conceptualization of the MTL as a memory space, representing both spatial- and nonspatial information to plan future actions and predict their outcomes.SIGNIFICANCE STATEMENT Using rare microwire recordings, we studied the representation of spatial, semantic, and temporal information in the human MTL. Our findings demonstrate that subjects acquire a cognitive map that simultaneously represents the spatial and semantic relations between landmarks. We further show that the same learned representation is used to predict future states, implicating MTL cell assemblies as the building blocks of prospective memory functions.

Differentiation of subclinical and clinical electrographic events in long-term electroencephalographic recordings.

OBJECTIVE: With the advent of ultra-long-term recordings for monitoring of epilepsies, the interpretation of results of isolated electroencephalographic (EEG) recordings covering only selected brain regions attracts considerable interest. In this context, the question arises of whether detected ictal EEG patterns correspond to clinically manifest seizures or rather to purely electrographic events, that is, subclinical events. METHODS: EEG patterns from 268 clinical seizures and 252 subclinical electrographic events from 50 patients undergoing video-EEG monitoring were analyzed. Features extracted included predominant frequency band, duration, association with rhythmic muscle artifacts, spatial extent, and propagation patterns. Classification using logistic regression was performed based on data from the whole dataset of 10-20 system EEG recordings and from a subset of two temporal electrode contacts. RESULTS: Correct separation of clinically manifest and purely electrographic events based on 10-20 system EEG recordings was possible in up to 83.8% of events, depending on the combination of features included. Correct classification based on two-channel recordings was only slightly inferior, achieving 78.6% accuracy; 74.4% and 74.8%, respectively, of events could be correctly classified when using duration alone with either electrode set, although classification accuracies were lower for some subgroups of seizures, particularly focal aware seizures and epileptic arousals. SIGNIFICANCE: A correct classification of subclinical versus clinical EEG events was possible in 74%-83% of events based on full EEG recordings, and in 74%-78% when considering only a subset of two electrodes, matching the channel number available from new implantable diagnostic devices. This is a promising outcome, suggesting that ultra-long-term low-channel EEG recordings may provide sufficient information for objective seizure diaries. Intraindividual optimization using high numbers of ictal events may further improve separation, provided that supervised learning with external validation is feasible.

Diagnostic yield and limitations of in-hospital documentation in patients with epilepsy.

OBJECTIVE: To determine the diagnostic yield of in-hospital video-electroencephalography (EEG) monitoring to document seizures in patients with epilepsy. METHODS: Retrospective analysis of electronic seizure documentation at the University Hospital Freiburg (UKF) and at King's College London (KCL). Statistical assessment of the role of the duration of monitoring, and subanalyses on presurgical patient groups and patients undergoing reduction of antiseizure medication. RESULTS: Of more than 4800 patients with epilepsy undergoing in-hospital recordings at the two institutions since 2005, seizures with documented for 43% (KCL) and 73% (UKF).. Duration of monitoring was highly significantly associated with seizure recordings (p < .0001), and presurgical patients as well as patients with drug reduction had a significantly higher diagnostic yield (p < .0001). Recordings with a duration of >5 days lead to additional new seizure documentation in only less than 10% of patients. SIGNIFICANCE: There is a need for the development of new ambulatory monitoring strategies to document seizures for diagnostic and monitoring purposes for a relevant subgroup of patients with epilepsy in whom in-hospital monitoring fails to document seizures.

Interictal spikes with and without high-frequency oscillation have different single-neuron correlates.

Interictal epileptiform discharges (IEDs) are a widely used biomarker in patients with epilepsy but lack specificity. It has been proposed that there are truly epileptogenic and less pathological or even protective IEDs. Recent studies suggest that highly pathological IEDs are characterized by high-frequency oscillations (HFOs). Here, we aimed to dissect these 'HFO-IEDs' at the single-neuron level, hypothesizing that the underlying mechanisms are distinct from 'non-HFO-IEDs'. Analysing hybrid depth electrode recordings from patients with temporal lobe epilepsy, we found that single-unit firing rates were higher in HFO- than in non-HFO-IEDs. HFO-IEDs were characterized by a pronounced pre-peak increase in firing, which coincided with the preferential occurrence of HFOs, whereas in non-HFO-IEDs, there was only a mild pre-peak increase followed by a post-peak suppression. Comparing each unit's firing during HFO-IEDs to its baseline activity, we found many neurons with a significant increase during the HFO component or ascending part, but almost none with a decrease. No such imbalance was observed during non-HFO-IEDs. Finally, comparing each unit's firing directly between HFO- and non-HFO-IEDs, we found that most cells had higher rates during HFO-IEDs and, moreover, identified a distinct subset of neurons with a significant preference for this IED subtype. In summary, our study reveals that HFO- and non-HFO-IEDs have different single-unit correlates. In HFO-IEDs, many neurons are moderately activated, and some participate selectively, suggesting that both types of increased firing contribute to highly pathological IEDs.

Reactivated Spatial Context Guides Episodic Recall.

The medial temporal lobe (MTL) is known as the locus of spatial coding and episodic memory, but the interaction between these cognitive domains as well as the extent to which they rely on common neurophysiological mechanisms is poorly understood. Here, we use intracranial electroencephalography and a hybrid spatial-episodic memory task (29 subjects, 15 female) to determine how spatial information is dynamically reactivated in subregions of the human MTL and how this reactivation guides recall of episodic information. Our results implicate theta oscillations across the MTL as a common neurophysiological substrate for spatial coding in navigation and episodic recall. We further show that our index of retrieved spatial context is high in the hippocampus (HC) in an early time window preceding recall. Closer to recall, it decreases in the HC and increases in the parahippocampal gyrus. Finally, we demonstrate that hippocampal theta phase modulates parahippocampal gamma amplitude during retrieval of spatial context, suggesting a role for cross-frequency coupling in coding and transmitting retrieved spatial information.SIGNIFICANCE STATEMENT By recording from the human medial temporal lobe (MTL) while subjects recall items experienced in a virtual environment, we establish a direct relation between the strength of theta activity during memory search and the extent to which memories are organized by their spatial locations. We thereby pinpoint a role for theta oscillations in accessing the "cognitive map" during episodic retrieval and further highlight the dynamic interplay of hippocampus and extrahippocampal MTL in representing retrieved spatial context. Our results provide an important step toward a unified theory of MTL function encompassing its role in spatial navigation and episodic memory.

Mossy fiber sprouting into the hippocampal region CA2 in patients with temporal lobe epilepsy.

Hippocampal sclerosis (HS) in Temporal Lobe Epilepsy (TLE) shows neuronal death in cornu ammonis (CA)1, CA3, and CA4. It is known that granule cells and CA2 neurons survive and their axons, the mossy fibers (MF), lose their target cells in CA3 and CA4 and sprout to the granule cell layer and molecular layer. We examined in TLE patients and in a mouse epilepsy model, whether MF sprouting is directed to the dentate gyrus or extends to distant CA regions and whether sprouting is associated with death of target neurons in CA3 and CA4. In 319 TLE patients, HS was evaluated by Wyler grade and International League against Epilepsy (ILAE) types using immunohistochemistry against neuronal nuclei (NeuN). Synaptoporin was used to colocalize MF. In addition, transgenic Thy1-eGFP mice were intrahippocampally injected with kainate and sprouting of eGFP-positive MFs was analyzed together with immunocytochemistry for regulator of G-protein signaling 14 (RGS14). In human HS Wyler III and IV as well as in ILAE 1, 2, and 3 specimens, we found synaptoporin-positive axon terminals in CA2 and even in CA1, associated with the extent of granule cell dispersion. Sprouting was seen in cases with cell death of target neurons in CA3 and CA4 (classical severe HS ILAE type 1) but also without this cell death (atypical HS ILAE type 2). Similarly, in epileptic mice eGFP-positive MFs sprouted to CA2 and beyond. The presence of MF terminals in the CA2 pyramidal cell layer and in CA1 was also correlated with the extent of granule cell dispersion. The similarity of our findings in human specimens and in the mouse model highlights the importance and opens up new chances of using translational approaches to determine mechanisms underlying TLE.

Epilepsy surgery: Late seizure recurrence after initial complete seizure freedom.

OBJECTIVE: This study was undertaken to improve understanding of late relapse following epilepsy surgery in pharmacoresistant epilepsy. METHODS: Retrospective comparison was made of 99 of 1278 patients undergoing surgery during 1999-2015 with seizure relapses after at least 2 years of complete seizure freedom with matched controls experiencing continued long-term seizure freedom. Univariate and multivariate analyses were performed. RESULTS: With a mean follow-up of 9.7 years, mean time to seizure relapse was 56.6 months. In multivariate analysis, incomplete resection based on magnetic resonance imaging (MRI), bilateral lesions on preoperative MRI, and epilepsy onset in the first year of life carried a significantly higher risk of late relapse. In patients with late relapse, additional functional imaging with positron emission tomography had been performed significantly more often. Although the differences were not significant in multivariate analysis, doses of antiepileptic drugs were higher in the relapse group preoperatively and in the first 24 months and complete withdrawal was more frequent in the control group (68% vs. 51%). Regarding seizure frequency, most patients had mild seizure relapse (single relapse seizure or <1/month). SIGNIFICANCE: In our predominantly lesional cohort, complete resection of the MRI lesion is the most important factor to maintain long-term seizure freedom. Two patterns of recurrence were identified: (1) incomplete resected lesions with seizure generation in proximity to the initial resection and (2) epileptogenic networks not detected preoperatively or evolving in the postoperative interval and manifesting with new clinical and diagnostic features.

Scalp electroencephalographic biomarkers in epilepsy patients with focal cortical dysplasia.

OBJECTIVE: To assess scalp electroencephalographic (EEG) patterns as possible biomarkers for an underlying focal cortical dysplasia (FCD) in patients with structural epilepsy. METHODS: Scalp electroencephalograms (EEGs) of epilepsy patients with histologically confirmed diagnosis of FCD type I or II (n = 71, age = 3-66 years, 28 female) and of controls with other underlying pathologies (n = 43, age = 2-60 years, 16 female) were retrospectively evaluated regarding the presence or absence of 12 scalp EEG patterns previously reported to be associated with FCD. Furthermore, 2 subgroups of these biomarkers with common characteristics were also analyzed. Each of the 12 biomarkers was tested for association with FCD by comparing the presence of each feature in FCD patients and controls using Fisher exact test. RESULTS: A significant association with FCD as underlying etiology was found for 6 of 12 previously reported biomarkers. With decreasing odds ratios, these were continuous epileptiform discharges, 2 types of rhythmic epileptiform discharges, polyspikes, frequent rhythmic bursting epileptiform activity, and repetitive discharges as well as the subgroups containing repetitive activity and polyspikes, respectively. Presence of EEG biomarkers was independent of a visible underlying magnetic resonance imaging-visible lesion, and had similar prevalence with FCD I and II. Individual biomarkers had specificities of 65 to 98% and sensitivities of 17 to 61% for an underlying FCD, and combinations of EEG biomarkers achieved 100% specificity. INTERPRETATION: This study confirms that there are several surface EEG biomarkers significantly associated with an underlying cortical dysplasia. These biomarkers may aid in localizing suspicious brain regions and provide evidence for dysplastic brain tissue also in nonlesional patients of either histological FCD subtype. Ann Neurol 2018;84:564-575.

Posterior cortex epilepsy surgery in childhood and adolescence: Predictors of long-term seizure outcome.

OBJECTIVE: We aimed to investigate the long-term seizure outcome of children and adolescents who were undergoing epilepsy surgery in the parietooccipital cortex and determine their predictive factors. METHODS: We retrospectively analyzed the data of 50 consecutive patients aged 11.1 (mean) ± 5.1 (standard deviation) years at surgery. All patients but one had a magnetic resonance imaging (MRI)-visible lesion. Resections were parietal in 40%, occipital in 32%, and parietooccipital in 28% cases; 24% patients additionally underwent a resection of the posterior border of the temporal lobe. Etiology included focal cortical dysplasia in 44%, benign tumors (dysembryoplastic neuroepithelial tumor, ganglioglioma, angiocentric glioma, and pilocystic astrocytoma) in 32%, peri- or postnatal ischemic lesions in 16%, and tuberous sclerosis in 8% cases. RESULTS: At last follow-up (mean 8 years, range 1.5-18 years), 60% patients remained seizure-free (Engel class I): 30% had discontinued and 20% had reduced antiepileptic drugs. Most seizure recurrences (71%) occurred within the first 6 months, and only three patients presented with seizures ≥2 years after surgery. Independent predictors of seizure recurrence included left-sided as well as parietal epileptogenic zones and resections. Longer epilepsy duration to surgery was identified as the only modifiable independent predictor of seizure recurrence. SIGNIFICANCE: Our study demonstrates that posterior cortex epilepsy surgery is highly effective in terms of lasting seizure control and antiepileptic drug cessation in selected pediatric candidates. Most importantly, our data supports the early consideration of surgical intervention in children and adolescents with refractory posterior cortex epilepsy.

Long-term seizure outcome in 211 patients with focal cortical dysplasia.

OBJECTIVE: Focal cortical dysplasia (FCD) is currently recognized as the most common cause of neocortical pharmacoresistant epilepsy. Epilepsy surgery has become an increasingly successful treatment option. Herein, the largest patient cohort reported to date is analyzed regarding long-term outcome and factors relevant for long-term seizure control. METHODS: Two hundred eleven children and adults undergoing epilepsy surgery for histologically proven FCD and a follow-up period of 2-12 years were analyzed regarding the longitudinal course of seizure control, effects of FCD type, localization, magnetic resonance imaging (MRI), timing of surgery, and postoperative antiepileptic treatment. RESULTS: After 1 year, Engel class I outcome was achieved in 65% of patients and the percentage of seizure-free patients remained stable over the following (up to 12) years. Complete resection of the assumed epileptogenic area, lower age at surgery, and unilobar localization were positive prognostic indicators of long-term seizure freedom. Seizure recurrence was 12% after the first year, whereas 8% achieved late seizure freedom either following additional introduction of antiepileptic drugs (AEDs) (4%), a reoperation (2%), or a running down phenomenon (2%). Thirty-nine percent of patients had a reduction of AED from polytherapy to monotherapy or a complete cessation of AED treatment. Late seizure relapse was seen in nine patients during reduction of AEDs (i.e., in 12% of all patients with AED tapering); in four of them seizures persisted after reestablishment of antiepileptic medication. SIGNIFICANCE: Postoperative long-term seizure outcome was favorable in patients with FCD and remained stable in 80% of patients after the first postoperative year. Several preoperative factors revealed to be predictive for the postoperative outcome and may help in the preoperative counseling of patients with FCD and in the selection of ideal candidates for epilepsy surgery.

Simultaneous subdural and scalp EEG correlates of frontal lobe epileptic sources.

OBJECTIVE: To assess the visibility and detectability in scalp electroencephalography (EEG) of cortical sources in frontal lobe epilepsy (FLE) as to their localization, and the extent and amplitude of activation. METHODS: We analyzed the simultaneous subdural and scalp interictal EEG recordings of 14 patients with refractory frontal lobe epilepsy (FLE) associated with focal cortical dysplasia. Subdural spike types were identified and averaged for source localization and detection of their scalp EEG correlates. Both raw and averaged scalp EEG segments were reviewed for spikes, blinded to subdural segments. We further analyzed the correlation of spike-to-background amplitude ratios in subdural and scalp EEG. RESULTS: We identified 36 spike types in subdural EEG, corresponding to 29 distinct sources. Four of 29 sources were visible by visual evaluation of scalp EEG and six additional sources were detectable after averaging: four in the medial frontal, two in the dorsolateral gyri, two in the depth of dorsolateral sulci, and two in the basal frontal region. Cortical sources generating scalp-detectable spikes presented a median of 6 cm(2) of activated cortical convexity surface and a subdural spike-to-background-amplitude ratio >8. These sources were associated with a higher number of activated subdural grid contacts and a higher subdural spike-to-background amplitude ratio than sources generating non-scalp-detectable spikes. SIGNIFICANCE: Not only dorsolateral but also basal and medial sources can be detectable in FLE. This is the first in vivo demonstration derived from simultaneous subdural and scalp EEG recordings of the complementary significance of extensive source activation and higher subdural spike-to-background amplitude ratio in the detection of cortical sources in FLE.

Theta-phase locking of single neurons during human spatial memory.

The precise timing of single-neuron activity in relation to local field potentials may support various cognitive functions. Extensive research in rodents, along with some evidence in humans, suggests that single-neuron activity at specific phases of theta oscillations plays a crucial role in memory processes. Our fundamental understanding of such theta-phase locking in humans and its dependency on basic electrophysiological properties of the local field potential is still limited, however. Here, using single-neuron recordings in epilepsy patients performing a spatial memory task, we thus aimed at improving our understanding of factors modulating theta-phase locking in the human brain. Combining a generalized-phase approach for frequency-adaptive theta-phase estimation with time-resolved spectral parameterization, our results show that theta-phase locking is a strong and prevalent phenomenon across human medial temporal lobe regions, both during spatial memory encoding and retrieval. Neuronal theta-phase locking increased during periods of elevated theta power, when clear theta oscillations were present, and when aperiodic activity exhibited steeper slopes. Theta-phase locking was similarly strong during successful and unsuccessful memory, and most neurons activated at similar theta phases between encoding and retrieval. Some neurons changed their preferred theta phases between encoding and retrieval, in line with the idea that different memory processes are separated within the theta cycle. Together, these results help disentangle how different properties of local field potentials and memory states influence theta-phase locking of human single neurons. This contributes to a better understanding of how interactions between single neurons and local field potentials may support human spatial memory.

Ripple-locked coactivity of stimulus-specific neurons and human associative memory.

Associative memory enables the encoding and retrieval of relations between different stimuli. To better understand its neural basis, we investigated whether associative memory involves temporally correlated spiking of medial temporal lobe (MTL) neurons that exhibit stimulus-specific tuning. Using single-neuron recordings from patients with epilepsy performing an associative object-location memory task, we identified the object-specific and place-specific neurons that represented the separate elements of each memory. When patients encoded and retrieved particular memories, the relevant object-specific and place-specific neurons activated together during hippocampal ripples. This ripple-locked coactivity of stimulus-specific neurons emerged over time as the patients' associative learning progressed. Between encoding and retrieval, the ripple-locked timing of coactivity shifted, suggesting flexibility in the interaction between MTL neurons and hippocampal ripples according to behavioral demands. Our results are consistent with a cellular account of associative memory, in which hippocampal ripples coordinate the activity of specialized cellular populations to facilitate links between stimuli.

Co-localizing linguistic and musical syntax with intracranial EEG.

Despite general agreement on shared syntactic resources in music and language, the neuroanatomical underpinnings of this overlap remain largely unexplored. While previous studies mainly considered frontal areas as supramodal grammar processors, the domain-general syntactic role of temporal areas has been so far neglected. Here we capitalized on the excellent spatial and temporal resolution of subdural EEG recordings to co-localize low-level syntactic processes in music and language in the temporal lobe in a within-subject design. We used Brain Surface Current Density mapping to localize and compare neural generators of the early negativities evoked by violations of phrase structure grammar in both music and spoken language. The results show that the processing of syntactic violations relies in both domains on bilateral temporo-fronto-parietal neural networks. We found considerable overlap of these networks in the superior temporal lobe, but also differences in the hemispheric timing and relative weighting of their fronto-temporal constituents. While alluding to the dissimilarity in how shared neural resources may be configured depending on the musical or linguistic nature of the perceived stimulus, the combined data lend support for a co-localization of early musical and linguistic syntax processing in the temporal lobe.

Seizure control and developmental trajectories after hemispherotomy for refractory epilepsy in childhood and adolescence.

PURPOSE: To evaluate the seizure control and developmental outcomes after hemispherotomy for refractory epilepsy in childhood and to identify their predictive factors. METHODS: We retrospectively studied the clinical courses and outcomes of 52 children with refractory epilepsy who underwent hemispherotomy in the Epilepsy Center Freiburg between 2002 and 2011. KEY FINDINGS: Mean age at epilepsy onset was 1.8 years (range 0-8 years) and mean age at surgery was 6.7 years (range 6 months-18 years). The underlying etiology was congenital in 22 (42%) children, acquired in 24 (46%), and progressive in 6 (12%). At final follow-up of 1-9.8 years (mean 3.3), 43 children (83%) were seizure-free. Seizure outcome was not correlated to etiology, with the exception of hemimegalencephaly that was linked to poor seizure control. Presurgical development was impaired in all but one child. Postsurgical development highly correlated with presurgical development. Patients with acquired or progressive etiology, later epilepsy onset, and subsequent later surgery exhibited higher presurgical developmental status that substantially determined postoperative developmental outcome. Improved postsurgical development was determined by acquired etiology and seizure freedom off antiepileptic drugs. SIGNIFICANCE: In our study, most of the selected children and adolescents achieved seizure freedom, including those with congenital etiology. Developmental outcomes, however, were superior in patients with acquired etiology and older age at surgery, underscoring that it is never too late to reap the benefits of this procedure in terms of both epilepsy and development.

Cyclical underreporting of seizures in patient-based seizure documentation.

OBJECTIVE: Circadian and multidien cycles of seizure occurrence are increasingly discussed as to their biological underpinnings and in the context of seizure forecasting. This study analyzes if patient reported seizures provide valid data on such cyclical occurrence. METHODS: We retrospectively studied if circadian cycles derived from patient-based reporting reflect the objective seizure documentation in 2003 patients undergoing in-patient video-EEG monitoring. RESULTS: Only 24.1% of more than 29000 seizures documented were accompanied by patient notifications. There was cyclical underreporting of seizures with a maximum during nighttime, leading to significant deviations in the circadian distribution of seizures. Significant cyclical deviations were found for focal epilepsies originating from both, frontal and temporal lobes, and for different seizure types (in particular, focal unaware and focal to bilateral tonic-clonic seizures). INTERPRETATION: Patient seizure diaries may reflect a cyclical reporting bias rather than the true circadian seizure distributions. Cyclical underreporting of seizures derived from patient-based reports alone may lead to suboptimal treatment schemes, to an underestimation of seizure-associated risks, and may pose problems for valid seizure forecasting. This finding strongly supports the use of objective measures to monitor cyclical distributions of seizures and for studies and treatment decisions based thereon.

Trends in referral patterns to presurgical evaluation at a European reference center.

PURPOSE: To determine if growing evidence for epilepsy surgery as an early treatment option is reflected in the decrease of latencies between epilepsy onset and referral for presurgical evaluation METHODS: Retrospective analysis of latencies in 1646 patients (children and adults) from the time of epilepsy diagnosis to first presurgical workup in the period from 1999 to 2019 based on electronic patient charts at a tertiary epilepsy center. Time spans 1999-2009 and 2010-2019, prior to and following the ILAE definition of pharmacoresistance, and the role of etiological factors were assessed. RESULTS: Over the whole period, the mean latency between diagnosis and a presurgical workup was 15.3 y. There was a significant reduction in the latencies between the periods 1999-2009 (16.9 y) and 2010-2019 (13.4 y), (p < 0.0001). In a linear regression analysis, the latency decreased by 2.6 months/year from 17.4 in 1999 to 13.1 y in 2019 (p < 0.001). Subgroup analyses showed significant decreases in latency to presurgical evaluation in patients with hippocampal sclerosis from 24.4 to 19.5 y, in malformations of cortical development from 16.4 to 13.2 y, and in nonlesional patients from 18.1 to 12.8 y, in contrast to patients with MR evidence for brain tumors with similar latencies across time (10.5 vs. 9.5 y, n.s.). CONCLUSION: The reduction of the time span to a first presurgical evaluation was highly significant over time, yet moderate in its degree. Overall, the aim of early diagnostic evaluation for epilepsy surgery options after established pharmacoresistance was only achieved for a minority of patients.

Occipital lobe epilepsy with fear as leading ictal symptom.

Ictal fear is a semiological feature which is commonly associated with mesial temporal lobe epilepsy. Here, we describe fear as a leading symptom in cryptogenic occipital lobe epilepsy. In a patient with negative MRI findings, intracranial EEG recordings documented a strict correlation between habitual ictal anxiety attacks and both spontaneous and stimulation-induced epileptic activity in a right occipital epileptogenic area with subsequent spreading to the symptomatogenic zone in the amygdala. Circumscribed occipital topectomy led to seizure freedom. Episodes of non-epileptic fear ceased shortly afterwards. This report provides insight into pathways of propagation of epileptic activity, illustrates different etiologies of pathologic fear and underlines the importance of ictal EEG recordings.

Ictal semiology of epileptic seizures with insulo-opercular genesis.

OBJECTIVE: Epileptic seizures with insular genesis are often difficult to distinguish from those originating in the temporal lobe due to their complex and variable semiology. Here, we analyzed differentiating characteristics in the clinical spectrum of insulo-opercular seizures. METHODS: Ictal semiology in patients with a diagnosis of insulo-opercular epilepsy (IOE) based on imaging of epileptogenic lesions or electrophysiological evidence of an insulo-opercular seizure origin was retrospectively analyzed and compared to age-matched controls with mesial temporal lobe epilepsy (MTE). RESULTS: Forty-six IOE and 46 matched MTE patients were included. The most prominent ictal features in IOE were focal motor phenomena in 80.4% of these patients. Somatosensory sensations, version, tonic and clonic features, when present, were more frequent contralateral to the SOZ in MTE patients, while they occurred about equally often ipsilateral and contralateral to the SOZ in IOE patients. Ipsilateral manual automatisms were significantly more frequent in MTE patients than in IOE (p = 0.010). Multivariate analysis correctly identified IOE in 78.3% and MTE in 84.8% using five semiologic features (Chi-square = 53.79 with 5 degrees of freedom, p < 0.0001). A subanalysis comparing patients with purely insular lesions with MTE patients using only the earliest ictal signs showed that somatosensory sensations are significantly more frequent in insular epilepsy (p = 0.010), while automatisms were significantly more frequent in MTE patients (p = 0.06). SIGNIFICANCE: Our study represents the first in-depth analysis of ictal semiology in IOE compared to MTE. Use of these differentiating characteristics can serve for a correct syndrome classification and to steer appropriate diagnostic and local therapeutic procedures.

Hippocampal gamma oscillations increase with memory load.

Although the hippocampus plays a crucial role in encoding and retrieval of contextually mediated episodic memories, considerable controversy surrounds the role of the hippocampus in short-term or working memory. To examine both hippocampal and neocortical contributions to working memory function, we recorded electrocorticographic activity from widespread cortical and subcortical sites as 20 neurosurgical patients performed working memory tasks. These recordings revealed significant increases in 48-90 Hz gamma oscillatory power with memory load for two classes of stimuli: letters and faces. Sites exhibiting gamma increases with memory load appeared primarily in the hippocampus and medial temporal lobe. These findings implicate gamma oscillatory activity in the maintenance of both letters and faces in working memory and provide the first direct evidence for modulation of hippocampal gamma oscillations as humans perform a working memory task.