Mesial Frontal Regions Research Articles

Cortical Synchrony and Information Flow during Transition from Wakefulness to Light Non-Rapid Eye Movement Sleep.

Sleep is a highly stereotyped phenomenon, requiring robust spatiotemporal coordination of neural activity. Understanding how the brain coordinates neural activity with sleep onset can provide insights into the physiological functions subserved by sleep and the pathologic phenomena associated with sleep onset. We quantified whole-brain network changes in synchrony and information flow during the transition from wakefulness to light non-rapid eye movement (NREM) sleep, using MEG imaging in a convenient sample of 14 healthy human participants (11 female; mean 63.4 years [SD 11.8 years]). We furthermore performed computational modeling to infer excitatory and inhibitory properties of local neural activity. The transition from wakefulness to light NREM was identified to be encoded in spatially and temporally specific patterns of long-range synchrony. Within the delta band, there was a global increase in connectivity from wakefulness to light NREM, which was highest in frontoparietal regions. Within the theta band, there was an increase in connectivity in fronto-parieto-occipital regions and a decrease in temporal regions from wakefulness to Stage 1 sleep. Patterns of information flow revealed that mesial frontal regions receive hierarchically organized inputs from broad cortical regions upon sleep onset, including direct inflow from occipital regions and indirect inflow via parieto-temporal regions within the delta frequency band. Finally, biophysical neural mass modeling demonstrated changes in the anterior-to-posterior distribution of cortical excitation-to-inhibition with increased excitation-to-inhibition model parameters in anterior regions in light NREM compared with wakefulness. Together, these findings uncover whole-brain corticocortical structure and the orchestration of local and long-range, frequency-specific cortical interactions in the sleep-wake transition.SIGNIFICANCE STATEMENT Our work uncovers spatiotemporal cortical structure of neural synchrony and information flow upon the transition from wakefulness to light non-rapid eye movement sleep. Mesial frontal regions were identified to receive hierarchically organized inputs from broad cortical regions, including both direct inputs from occipital regions and indirect inputs via the parieto-temporal regions within the delta frequency range. Biophysical neural mass modeling revealed a spatially heterogeneous, anterior-posterior distribution of cortical excitation-to-inhibition. Our findings shed light on the orchestration of local and long-range cortical neural structure that is fundamental to sleep onset, and support an emerging view of cortically driven regulation of sleep homeostasis.

Post-COVID-19 Sydenham Chorea: A Case Report

Background: Sydenham chorea, or rheumatic chorea, is a movement disorder that is more prevalent among young people, with a mean age at symptom onset between 8 and 9 years. The condition is more common in females. Sydenham chorea is associated with rheumatic fever and is considered the most common cause of acute chorea in children. We believe that the present case is worth reporting since the occurrence of Sydenham chorea as a post-COVID-19 sequela has not been described in Brazil. Case Presentation: We report here the case of a 14-year-old girl with symptoms of acute chorea that emerged 15 days after treatment resolution of COVID-19 (SARS-CoV-2 or severe acute respiratory syndrome coronavirus 2). Brain computed tomography (CT) and magnetic resonance imaging scans showed no changes, and the laboratory tests revealed no signs of an active infectious process. In contrast, neurological positron-emission tomography/CT showed mild glycolytic hypometabolism in the bilateral mesial frontal region. Administration of an oral anticonvulsant resulted in a marked improvement in her symptoms. Conclusion: Despite major efforts of the scientific community for discovering treatments, preventive methods, mechanisms of action, and possible sequelae of SARS-CoV-2, there is still a long way to go to better understand this devastating pathological agent that has affected the global population.

Trans-Interhemispheric Stereoelectroencephalography Depth Electrode Placement for Mesial Frontal Lobe Explorations in Medically Refractory Epilepsy: A Technical Note and Case Series.

Stereoelectroencephalography (SEEG) is an established and safe methodology for extra-operative invasive monitoring in patients with medical refractory epilepsy. SEEG has several advantages such as the ability to record deep cortical structures, mapping the epileptogenic zone in a three-dimensional manner, and analyze bihemispheric regions without the need for bilateral craniotomies. In patients with bilateral hemispheric hypotheses, especially the mesial surface of frontal lobes, bilateral lead placement is compulsory to further define and localize the epileptogenic zone. In this particular cohort of patients, bilateral monitoring may be accomplished from a single entry point using trans-interhemispheric placement of the electrodes. The use of trans-interhemispheric monitoring offers several advantages including sparing the need for additional leads. To test the hypothesis that, given the lack of the falx as a limiting structure in the ventral and mesial frontal lobe regions, trans-interhemispheric SEEG placement is feasible and a potential benefit for the SEEG method. We report on 6 patients who underwent bilateral monitoring using trans-interhemispheric SEEG lead placement and discuss the operative technique. Six patients underwent trans-interhemispheric monitoring, with a median of 3 leads per patient (19 total). Trajectory error was minimal (<0.3 mm), and operating room time was comparable with that in previous reports. All leads were placed without adverse events, mislocalization, electrode hemorrhages, or any other complications. All patients had successful localization of the epileptogenic zone. Trans-interhemispheric SEEG to monitor the mesial wall of frontal lobe regions is technically feasible. No adverse events were observed, suggesting a favorable safety profile.

Long-term follow-up of vagus nerve stimulation in drug-resistant KCNT1-related epilepsy: a case presentation

BackgroundThe KCNT1 gene encodes a Na+-activated K+ channel. Gain-of-function mutations of KCNT1 lead to autosomal dominant sleep-related hypermotor epilepsy, early-onset epileptic encephalopathy, focal epilepsy and other epileptic encephalopathies. In this paper, we report a boy carrying a KCNT1 gene mutation, who presented with drug-resistant focal-onset seizures. He had decreased seizure frequency and improvement of background changes in electroencephalography (EEG) after vagus nerve stimulation (VNS).Case presentationThe case was a nonverbal 9-year-old male who presented with drug-resistant focal-onset seizures since age 3 and had underwent VNS therapy for 2 years. He had hypermotor symptoms, automatism and bilateral asymmetric tonic seizures with cognitive decline and aphasis from age 3. The patient had a variety of seizure types that only occurred at night. The most common seizure type was automatisms, and ictal video EEG showed high-amplitude delta waves, followed by a fast rhythmic sharp activity in the mesial frontal and bitemporal regions. The patient was diagnosed with KCNT1-related epilepsy, epileptic encephalopathy and cognitive disorder. He was refractory to multiple anti-seizure medicines (ASM) and ketogenic diet. After VNS treatment at age 7, the frequency of seizures was reduced significantly and EEG was improved in background slowing.ConclusionsChildren with KCNT1-related epilepsy usually have early onset of disease, are nonverbal, and are refractory to ASM. This boy with drug-resistant KCNT1-related epilepsy showed significantly reduced seizure frequency after VNS. This report may provide reference for management of cases of KCNT1-related epilepsy.

Functional Reorganization of the Mesial Frontal Premotor Cortex in Patients With Supplementary Motor Area Seizures.

Direct cortical stimulation of the mesial frontal premotor cortex, including the supplementary motor area (SMA), is challenging in humans. Limited access to these brain regions impedes understanding of human premotor cortex functional organization and somatotopy. To test whether seizure onset within the SMA was associated with functional remapping of mesial frontal premotor areas in a cohort of patients with epilepsy who underwent awake brain mapping after implantation of interhemispheric subdural electrodes. Stimulation trials from 646 interhemispheric subdural electrodes were analyzed and compared between patients who had seizure onset in the SMA (n = 13) vs patients who had seizure onset outside of the SMA (n = 12). 1:1 matching with replacement between SMA and non-SMA data sets was used to ensure similar spatial distribution of electrodes. Centroids and 95% confidence regions were computed for clustered head, trunk, upper extremity, lower extremity, and vision responses. A generalized linear mixed-effects model was used to test for significant differences in the resulting functional maps. Clinical, radiographic, and histopathologic data were reviewed. After analyzing direct cortical stimulation trials from interhemispheric electrodes, we found significant displacement of the head and trunk responses in SMA compared with non-SMA patients ( P < .01 for both). These differences remained significant after accounting for structural lesions, preexisting motor deficits, and seizure outcome. The somatotopy of the mesial frontal premotor regions is significantly altered in patients who have SMA-onset seizures compared with patients who have seizure onset outside of the SMA, suggesting that functional remapping can occur in these brain regions.

Transient epileptic amnesia is significantly associated with discrete CA1-located hippocampal calcifications but not with atrophic changes on brain imaging

BackgroundThe exact etiology of transient epileptic amnesia (TEA) is currently unknown. In older individuals, common neurodegenerative dementias and small-vessel diseases (SVDs) could be major contributors. We examined these hypotheses on the basis of imaging analysis. MethodsIn total, 36 TEA patients were compared with 25 healthy controls for (1) cortical atrophic changes (in the mesial temporal, frontal, anterior temporal, and parietal regions) using four established MRI-based visual rating scales, and for (2) SVD evidence using two MRI-based visual rating scales (Fazekas and MARS scores). In 24 TEAs cases, there were also brain CT scans available that were compared with 57 controls for the presence of hippocampal calcifications (HCs). ResultsWe did not find significant differences in cortical atrophy between TEAs and controls, nor did we observe a different SVD brain load on MRI. However, TEAs were significantly associated (p < 0.01) with uni- or bilateral CA1-located HCs in half of the patients compared with the controls (less than 20 %). ConclusionsThis study argues in favor of a hippocampal-restricted SVD (as indicated by HCs) as one of the major etiologies of TEA, while neurodegenerative dementias are probably minor causes. It furthermore highlights the pivotal role of the CA1 hippocampal subfield in the pathophysiology of this syndrome.

Alterations of functional connectivity density in a Chinese family with a mild phenotype associated with a novel inherited variant of SCN8A

ObjectiveOnly a few heritable SCN8A variants have been described in patients with a mild phenotype of epilepsy. Here, we describe a Chinese family with a novel inherited SCN8A variant and investigate changes in spontaneous cerebral activity during the resting-state in magnetic resonance imaging (MRI)-negative patients with epilepsy and their unaffected siblings. MethodsA gene panel targeting 535 epilepsy genes was performed on the proband and his parents. The identified variant was confirmed in other affected members by Sanger sequencing. Resting-state functional MRI (fMRI) data were gathered from the family (4 affected individuals and 3 unaffected siblings) and 72 healthy controls (HCs). Functional connectivity density (FCD) was used to assess whether distant or local functional network changes occurred in patients with epilepsy. ResultsA heterozygous missense variant (c.4568C>A; p.A1523D) in SCN8A was identified in the Chinese family, with a total of 7 members who presented with a mild phenotype (childhood seizures and normal cognition). All patients remained seizure-free, and one patient remained seizure-free without medication. Increased FCD values in the thalamocortical network and basal ganglia network were observed in both patients with epilepsy and their unaffected siblings compared with the HCs. Direct comparison between SCN8A variant patients and unaffected siblings showed that more serious and distributed abnormal changes occurred in the mesial frontal regions of patients with epilepsy. ConclusionsWe identified a novel SCN8A variant with a mild familial epilepsy phenotype. A similar pattern of FCD alterations in patients and their unaffected siblings might represent an endophenotype of benign epilepsy associated with the SCN8A inherited variant, and more extensive alterations in mesial frontal regions may help us to further understand the pathogenesis of SCN8A-related mild epilepsy.

TB or not TB?

A 37-year-old man of Pakistani origin gave a 2-week history of worsening headache, confusion and seizures. He had recently returned from a trip to Pakistan. His only previous medical history...

Effortful verb retrieval from semantic memory drives beta suppression in mesial frontal regions involved in action initiation

The contribution of the motor cortex to the semantic retrieval of verbs remains a subject of debate in neuroscience. Here, we examined whether additional engagement of the cortical motor system was required when access to verbs semantics was hindered during a verb generation task. We asked participants to produce verbs related to presented noun cues that were either strongly associated with a single verb to prompt fast and effortless verb retrieval, or were weakly associated with multiple verbs and more difficult to respond to. Using power suppression of magnetoencephalography beta oscillations (15-30 Hz) as an index of cortical activation, we performed a whole-brain analysis in order to identify the cortical regions sensitive to the difficulty of verb semantic retrieval. Highly reliable suppression of beta oscillations occurred 250 ms after the noun cue presentation and was sustained until the onset of verbal response. This was localized to multiple cortical regions, mainly in the temporal and frontal lobes of the left hemisphere. Crucially, the only cortical regions where beta suppression was sensitive to the task difficulty, were the higher order motor areas on the medial and lateral surfaces of the frontal lobe. Stronger activation of the premotor cortex and supplementary motor area accompanied the effortful verb retrieval and preceded the preparation of verbal responses for more than 500 ms, thus, overlapping with the time window of verb retrieval from semantic memory. Our results suggest that reactivation of verb-related motor plans in higher order motor circuitry promotes the semantic retrieval of target verbs.

B.04 Insight into the mesial frontal negative motor area: The girl with a very unusual interest in having her back patted

Background: Currently, there is limited insight in to the function of the mesial frontal negative motor area (NMA) and the anatomic structures implicated in its function. Methods: We present a patient with a Rett-like phenotype, refractory frontal lobe epilepsy, and reflexogenic seizures in which backpatting induced atonic seizures with a semiology resembling the patient falling asleep. The patient underwent video EEG monitoring and ictal/interictal SPECT imaging capturing the reflexogenic seizures. Iterative reconstruction was performed, with images co-registered to previously acquired MRI with subtraction Ictal-Interictal imaging co-registered to MRI. Results: Interictally, the patient’s EEG showed a slow background and right frontal spikes. Ictally, the patient had numerous subclinical frontal seizures. The reflexogenic seizures had an ictal pattern at the vertex (Cz) with the ictal SPECT imaging, showing hyperperfusion in the right mesial frontal region, both paramedian precentral and postcentral gyri, and right basal ganglia. Conclusions: Our findings support the hypothesis that the negative motor area may be activated by the primary sensory cortex; moreover, the ictal SPECT now suggests involvement of the basal ganglia in the NMA’s function.

T02. Impairment of consciousness induced by electrical cortical stimulation: Under-reported phenomenon or a disease-specific condition?

Although consciousness is commonly impaired in epileptic seizures, limited literature is available on loss of consciousness induced by electrical cortical stimulation (ECS) in humans undergoing intracranial EEG evaluations for localization of epileptic focus. Case-study and review of literature. We report a case of impairment of consciousness (IOC) induced by electrical cortical stimulation (ECS) of homologous regions within the lateral frontal convexities in a patient with medically intractable epilepsy. The patient had mixed features of idiopathic generalized and focal epilepsy. On intracranial EEG recording, interictal and ictal discharges showed a high degree of synchrony across widespread bilateral fronto-parietal areas. We identified regions in the lateral frontal lobes that reliably and produced loss of consciousness by ECS. This was accompanied by evoked EEG activity of admixed frequencies over the fronto-parietal, mesial frontal and temporal regions during stimulation and was not associated with after-discharges. Symptoms were immediately reversible upon cessation of stimulation. This finding suggests that focal cortical stimulation can disrupt widespread networks that underlie consciousness. Individuals with high degrees of speculated thalamo-frontal cortical connectivity might be more susceptible to this effect, and the findings highlight the importance of standardizing the testing of level of consciousness during mapping sessions. This report highlights the importance of testing for impairment of consciousness during sessions of electrical cortical stimulation. It also underlines the possibility that localized stimulation in some cases may produce widespread changes in brain physiology and in consciousness. Future prospective studiesmay elucidate the occurrence and prognostic value of impairment of consciousness during electrical cortical stimulation for mapping function.

18F-FDG PET in drug-resistant epilepsy due to focal cortical dysplasia type 2: additional value of electroclinical data and coregistration with MRI.

To assess the localizing value of 18F-FDG PET in patients operated on for drug-resistant epilepsy due to focal cortical dysplasia type 2 (FCD2). We analysed 18F-FDG PET scans from 103 consecutive patients (52 males, 7-65years old) with histologically proven FCD2. PET and MRI data were first reviewed by visual analysis blinded to clinical information and FCD2 location. The additional value of electroclinical data and PET/MRI coregistration was assessed by comparison with pathological results and surgical outcomes. Visual analysis of PET scans showed focal or regional hypometabolism corresponding to the FCD2 in 45 patients (44%), but the findings were doubtful or misleading in 37 patients and negative in 21. When considering electroclinical data, positive localization was obtained in 73 patients, and this increased to 85 (83%) after coregistration of PET and MRI data. Under the same conditions, MRI was positive in 61 patients (59%), doubtful in 15 and negative in 27. The additional value of PET was predominant in patients negative or doubtful on MRI, localizing the FCD2 in 35 patients (83%). Interobserver agreement correlated with the grade of hypometabolism: it was good in patients with mild to severe hypometabolism (82-95%), but moderate in those with subtle/doubtful hypometabolism (45%). The main factors influencing positive PET localization were the grade of hypometabolism and the size of the FCD2 (P < 0.0001). Misleading location (nine patients) was associated with a small FCD2 in the mesial frontal and central regions. Following limited cortical resection mainly located in extratemporal areas (mean follow-up 5.6years), a seizure-free outcome was achieved in 94% of patients, including Engel's class IA in 72%. In this series, 18F-FDG PET contributed to the localization of FCD2 in 83% of patients. This high localizing value was obtained by integration of electroclinical data and PET/MRI coregistration. This approach may help improve the surgical outcome in extratemporal epilepsy, even in patients negative on MRI.

Impairment of consciousness induced by bilateral electrical stimulation of the frontal convexity

We report a case of impairment of consciousness (IOC) induced by electrical cortical stimulation (ECS) of homologous regions within the lateral frontal convexities in a patient with medically intractable epilepsy. The patient had mixed features of idiopathic generalized and focal epilepsy. On intracranial EEG recording, interictal and ictal discharges showed a high degree of synchrony across widespread bilateral fronto-parietal areas. We identified regions in the lateral frontal lobes that reliably and produced loss of consciousness by ECS. This was accompanied by evoked EEG activity of admixed frequencies over the fronto-parietal, mesial frontal and temporal regions during stimulation and was not associated with after-discharges. Symptoms were immediately reversible upon cessation of stimulation. This finding suggests that focal cortical stimulation can disrupt widespread networks that underlie consciousness. Individuals with high degrees of speculated thalamo-frontal cortical connectivity might be more susceptible to this effect, and the findings highlight the importance of standardizing the testing of level of consciousness during mapping sessions.Although consciousness is commonly impaired in epileptic seizures, limited literature is available on loss of consciousness induced by electrical cortical stimulation (ECS) in humans undergoing intracranial EEG evaluations for localization of epileptic focus. One theory advocates the presence of consciousness ‘switch’ in subcortical structures. While this model is novel and simplistic, it has its inherent limitations. In this case study, we propose an alternative approach on the entity and discuss the complex circuits underlying it and correlate that with the electrophysiological findings and the pathophysiology of the phenotype of the disease and discuss potential causes for rarity of reports on the subject.

American Clinical Neurophysiology Society Guideline 3: A Proposal for Standard Montages to Be Used in Clinical EEG.

This revision to the EEG Guidelines is an update incorporating current electroencephalography technology and practice and was previously published as Guideline 6. A discussion of methodology for the appropriate selection of reference electrodes is added. In addition, montages are added to assist with localization of abnormal activity in mesial frontal and anterior temporal regions.

Pontine and cerebral atrophy in Lennox–Gastaut syndrome

ObjectivesLennox–Gastaut syndrome (LGS) is a severe epilepsy of childhood onset associated with intellectual disability and multiple seizure types. Characteristic interictal electrographic discharges include generalized paroxysmal fast activity and slow spike and wave, which we have previously shown recruit widespread areas of association cortex. We wished to determine whether patients with Lennox–Gastaut syndrome (LGS) have changes in cerebral volumes that match this pattern of cortical recruitment. MethodsHigh resolution T1 weighted structural MRI was collected from 10 patients with LGS and 10 age and sex matched controls. Voxel-based morphometry (VBM) was used to compare tissue volumes across the whole brain (grey matter, white matter and CSF) and pontine volume between patients and controls, as well as to identify other regions of maximal tissue loss. ResultsLGS patients showed a significant decrease in whole brain volume compared to controls. Cortical atrophy was prominent in the mesial frontal region and bilateral anterior temporal poles. White matter atrophy was widespread and included peri-central and premotor regions. Atrophy was prominent in the pons, particularly in the region of the reticular formation. Grey matter atrophy trended to progress with age. SignificanceGrey and white matter atrophy are a feature of Lennox–Gastaut syndrome. Grey matter atrophy is apparent in the mesial frontal lobe suggesting this region may be an important node in the epilepsy network of LGS. Atrophy maximal in the pons and cerebellum mimics the patterns of seizure spread that has been previously observed during tonic seizures. This supports the idea that the pons is a key part of the epilepsy network in LGS.

P3. Multimodal effective connectivity analysis reveals seizure focus and propagation in musicogenic epilepsy

Objective Dynamic causal modeling (DCM) is a method to non-invasively assess effective connectivity between brain regions. This is especially interesting in epilepsy where the identification of epileptic network dynamics is of great clinical interest. ‘Musicogenic epilepsy’ is a rare reflex epilepsy syndrome in which seizures can be specifically elicited by musical stimuli and thus represents a unique possibility to investigate complex human brain networks and test connectivity analysis tools. We investigated the temporal sequence of epileptic activity spread in a case of musicogenic epilepsy using DCM for fMRI, high-density (hd-) EEG and MEG and validated results with intracranial EEG recordings. Methods A patient with musicogenic seizures triggered by Rap music was examined using hd-EEG/fMRI and simultaneous 256-channel hd-EEG/MEG to characterize the epileptogenic focus and propagation effects using source analysis techniques and DCM. Results were validated with invasive EEG recordings. Results We recorded one seizure with hd-EEG/fMRI and four auras with hd-EEG/MEG. Consistent across all modalities, we observed activations in the right mesio-temporal region as well as bilateral mesial frontal regions ( Fig. 1 ) at seizure onset. Effective connectivity analysis of fMRI and hd-EEG/MEG indicated that right mesio-temporal neuronal activity drives changes in the frontal areas consistently in all three modalities ( Fig. 2 ), i.e. seizures seem to originate in the right mesio-temporal region and propagate to the frontal region. These results could be confirmed by invasive EEG recordings, which clearly identified the seizure onset zone in the right hippocampus with fast propagation of seizure activity to the mesial frontal lobes. Conclusions Using DCM for fMRI, hd-EEG and MEG we were able to correctly localize focus and propagation of epileptic activity and thereby characterize the underlying epileptic network in a patient with musicogenic epilepsy. The concordance between all three functional modalities validated by invasive monitoring is noteworthy, both for musicogenic seizures as well as for effective connectivity analysis in general.

Multimodal effective connectivity analysis reveals seizure focus and propagation in musicogenic epilepsy

Dynamic causal modeling (DCM) is a method to non-invasively assess effective connectivity between brain regions. ‘Musicogenic epilepsy’ is a rare reflex epilepsy syndrome in which seizures can be elicited by musical stimuli and thus represents a unique possibility to investigate complex human brain networks and test connectivity analysis tools. We investigated effective connectivity in a case of musicogenic epilepsy using DCM for fMRI, high-density (hd-) EEG and MEG and validated results with intracranial EEG recordings.A patient with musicogenic seizures was examined using hd-EEG/fMRI and simultaneous ‘256-channel hd-EEG’/‘whole head MEG’ to characterize the epileptogenic focus and propagation effects using source analysis techniques and DCM. Results were validated with invasive EEG recordings.We recorded one seizure with hd-EEG/fMRI and four auras with hd-EEG/MEG. During the seizures, increases of activity could be observed in the right mesial temporal region as well as bilateral mesial frontal regions. Effective connectivity analysis of fMRI and hd-EEG/MEG indicated that right mesial temporal neuronal activity drives changes in the frontal areas consistently in all three modalities, which was confirmed by the results of invasive EEG recordings. Seizures thus seem to originate in the right mesial temporal lobe and propagate to mesial frontal regions.Using DCM for fMRI, hd-EEG and MEG we were able to correctly localize focus and propagation of epileptic activity and thereby characterize the underlying epileptic network in a patient with musicogenic epilepsy. The concordance between all three functional modalities validated by invasive monitoring is noteworthy, both for epileptic activity spread as well as for effective connectivity analysis in general.

The role of the corpus callosum in seizure spread: MRI lesion mapping in oligodendrogliomas

Some patients with oligodendrogliomas have generalized tonic-clonic seizures (GTCS) while others have only partial seizures (PS). We investigated the relationship between tumour localization and seizure generalization using quantitative lesion mapping on magnetic resonance images. Twenty one patients with histologically proven oligodendrogliomas and GTCS (n=11) or PS (n=10) were studied. Data were acquired on a 3 Tesla MRI System. We performed lesion mapping techniques to compare the spatial distribution of oligodendrogliomas between patient groups, and quantitatively determined the extent to which lesions intersected each probabilistic regions-of-interest, including the cerebral lobes, thalamus, striatum, and genu of the corpus callosum. In patients experiencing GTCS, the greatest lesion load was observed in mesial frontal regions, including cortex connected to the genu. In contrast, the greatest lesion load in patients experiencing PS was observed more caudo-laterally in orbitofrontal and temporal lobes, but typically sparing cortex connected to the genu. The number of lesion intersections with genu region of interest was significantly greater in patients experiencing GTCS relative to patients with PS (p=0.03). There were no significant differences between patient groups with respect to lesion intersection with the individual cerebral lobes, thalamus and striatum, or with respect to overall oligodendroglioma size. Our data suggest that the genu of the corpus callosum may be a major pathway for seizure generalization in patients with oligodendrogliomas.

Professor Hans Otto Lüders

Professor Lüders has made significant contributions to Clinical Neurology and particularly to Epilepsy and Clinical Neurophysiology. Some of his most important contributions include the following: 1.He pioneered the use of chronically implanted, large plates of subdural electrodes in the presurgical evaluation of patient who were candidates for epilepsy surgery. These electrodes were used to record epileptic seizures and by electrical stimulation to establish the location of eloquent cortex. Lately he has also advocated the use in the USA of stereotactically implanted depth electrodes for presurgical evaluation of epilepsy patients who had deep seated epileptic foci which were impossible to assess with subdural electrodes. These techniques were imported from Europe. 2.Mapping studies with subdural electrodes led to the discovery of a number of cortical eloquent areas that had not been described before: a. The basal temporal language area located in the dominant fusiform gyrus. b. The "negative motor areas" located in the caudal region of the inferior frontal gyrus (bilaterally) and immediately in mesial frontal pre-SMA region (also bilaterally). He concluded that these "negative motor areas" most likely correspond to praxis regions. c. The dominant posterior fusiform gyrus which plays a crucial role in processing reading material. Stimulation of that area produces "alexia without agraphia". 3.He developed a new classification of epileptic seizures based exclusively on semiological ictal characteristics. With the development of the semiological seizure classification he also defined several new seizure types: a. Dialeptic seizures, b. Hypnopompic seizures, c. Hypomotor seizures. 4.Working with general epilepsy principles, he established the existence of 6 zones that characterize the epilepsies: the epileptogenic zone, the irritative zone, the seizure onset zone, the epileptogenic lesion, the symptomatogenic zone and functional deficit zone. 5.He described the ictal DC (direct current) shift seen at the beginning of focal seizures and its value for localization of the seizure onset zone.

Ventral Premotor Neurons Encoding Representations of Action during Self and Others’ Inaction

Our environment offers us a number of opportunities for action. However, sometimes we also have to refrain from acting, for example, when facing a "do not touch" sign placed over a desirable object on the shelf of a shop. Previous findings emphasized the role of mesial frontal and prefrontal regions in the inhibition of stimulus-driven motor responses [1-3], leading to the prediction that motor areas should not become active when one inhibits a motor response. Nevertheless, refraining from performing a specific action might require one to internally represent what one is not doing. Is the motor system simply inhibited in this condition, or does it play an active role in the representation of the withheld action? Here, we show that while the majority of macaque ventral premotor neurons remain silent when the monkey refrains from grasping an object, others, recorded simultaneously with the former, discharge both when the monkey grasps an object ("action") and when it refrains from doing so ("inaction"). The same effect has been shown to be present for mirror neurons [4]. Some of them, besides discharging during action observation, also fire when the observed agent refrains from acting. Notably, neurons discharging during inaction specifically encode either the monkey's own or other's inaction, not both. Our findings indicate that ventral premotor cortex encodes representations of our own or others' action not only when we perform or observe that action but also when its negation is represented.