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Purpose: Decision-making is crucial to daily life and can impact our society as well as economic conditions. Although the frontal lobes have been identified as important for decision-making, this capacity has only been studied to a limited extent in frontal lobe epilepsy and not at all after frontal lobe resection (FLR) for epilepsy. This study aimed to explore decision-making under ambiguity after FLR for epilepsy., Methods: Fourteen patients having undergone FLR for epilepsy completed the Iowa Gambling Task (IGT) which is a widely used tool to measure decision-making under ambiguity. Iowa Gambling Task scores included in the analysis were: total net score, separate scores from five blocks across the test, and a change score (last block of IGT minus first block). A group of healthy controls (n = 30) was used as a comparison. Associations between IGT and standardized neuropsychological methods for assessment of executive functions, self-rating questionnaires of mental health, fatigue, and behavior linked to frontal lobe dysfunction were also investigated., Results: The patient group performed inferior to controls at the final block of the IGT (p =.001).A group difference in IGT change scores was found (p =.005), reflectingthe absence of a positive change in performance over time for the FLR group compared to the control group. Correlations with tests of executive functions as well as self-rating scales were mainly statistically nonsignificant., Conclusions: This study shows that patients having undergone FLR for epilepsy have difficulties with decision-making under ambiguity. The performance illustrated a failure to learn throughout the task. Executive as well as emotional deficits may impact decision-making processes in this patient group and need to be considered in further studies. Prospective studies with larger cohorts are needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Frontal lobectomy is often used as a surgical treatment for frontal lobe epilepsy, especially when a large epileptogenic zone in the frontal lobe is inferred from preoperative evaluation. The frontal lobe is important for cognitive functions such as executive functions and verbal fluency, but the neuropsychological outcome after a frontal or prefrontal lobectomy that includes both the dorsolateral prefrontal cortex and ventral prefrontal cortex has not been studied thoroughly. In the present study, we evaluated neuropsychological outcomes after patients with frontal lobe epilepsy received a frontal or prefrontal lobectomy., Methods: We retrospectively reviewed the data of patients with frontal lobe epilepsy who underwent a frontal or prefrontal lobectomy that includes both the dorsolateral prefrontal cortex and ventral prefrontal cortex at 16 years or older from October 2004 to December 2014, with a minimum postoperative follow-up of 24 months. We analyzed and compared neuropsychological outcomes, including executive functions, verbal fluency, intelligence, and memory, before and after the operation., Results: Eighteen patients were 16 years or older and underwent pre- and postoperative (2 years after the operation) neuropsychological evaluations. Patients showed significant deterioration only on the Benton Visual Retention Test. Performance on tests of frontal lobe functions, such as executive function and verbal fluency, showed no significant deterioration., Conclusions: Overall cognitive performance, including functions widely thought to depend on the frontal lobe, is stable after a frontal or prefrontal lobectomy to treat frontal lobe epilepsy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Frontal lobe resection (FLR) is the second most common epilepsy surgery procedure in adults. Few studies address neuropsychological consequences after FLR. The aim of this study was to explore patients' and relatives' experiences of cognitive, emotional and social cognitive functioning after frontal lobe epilepsy surgery., Methods: Semi-structured interviews were held with 14 patients having gone through FLR as adults during the years 2000-2016 and 12 of their relatives. Interviews were audio-recorded, transcribed and analyzed with inductive qualitative content analysis., Results: Positive as well as negative consequences were described both by patients and relatives. Feelings of relief and an increased capacity to experience emotions of well-being were mainly experienced as related to seizure freedom. A newfound autonomy and a more grown-up identity as opposed to a self-image based on epilepsy was also highlighted. However, results also showed that even for seizure free patients, FLR could give rise to negative experiences, the most prominent of which were mental fatigue, lowered mood and social withdrawal. Coping strategies included planning ahead to avoid mental exhaustion. Over all, respondents considered that the epilepsy surgery had been a risk well worth taking and that positive consequences outweighed the negative ones., Conclusions: This study shows a range of positive as well as negative outcomes after FLR for epilepsy. The findings indicate that lowered mood and mental fatigue could affect the life situation in a negative way, regardless of seizure outcome. This is important to consider in the preoperative counselling of patients and their families, as well as in the postsurgical follow-up. It is also crucial that the epilepsy surgery team has the possibility to offer rehabilitation and support to families regarding these aspects after surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Frontal seizures are organized according to anatomo-functional subdivisions of the frontal lobe. Prefrontal seizures have been the subject of few detailed studies to date. The objective of this study was to identify subcategories of prefrontal seizures based on seizure onset quantification and to look for semiological differences., Methods: Consecutive patients who underwent stereoelectroencephalography (SEEG) for drug-resistant prefrontal epilepsy between 2000 and 2018 were included. The different prefrontal regions investigated in our patients were dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), dorsomedial prefrontal cortex (DMPFC), ventromedial prefrontal cortex (VMPFC), and orbitofrontal cortex (OFC). The seizure onset zone (SOZ) was determined from one or two seizures in each patient, using the epileptogenicity index (EI) method. The presence or absence of 16 clinical ictal manifestations was analyzed. Classification of prefrontal networks was performed using the k-means automatic classification method., Results: A total of 51 seizures from 31 patients were analyzed. The optimal clustering was 4 subgroups of prefrontal seizures: a "pure DLPF" group, a "pure VMPF" group, a "pure OFC" group, and a "global prefrontal" group. The first 3 groups showed a mean EI considered epileptogenic (>0.4) only in one predominant structure, while the fourth group showed a high mean EI in almost all prefrontal structures. The median number of epileptogenic structures per seizure (prefrontal or extrafrontal) was 5 for the "global prefrontal" group and 2 for the other groups. We found that the most common signs were altered consciousness, automatisms/stereotypies, integrated gestural motor behavior, and hyperkinetic motor behavior. We found no significant difference in the distribution of ictal signs between the different groups., Conclusion: Our study showed that although most prefrontal seizures manifest as a network of several anatomically distinct structures, we were able to determine a sublobar organization of prefrontal seizure onset with four groups., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

There is accumulating evidence for considerable overlap in preoperatively affected cognitive functions in patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE). The current study investigated whether it is possible to differentiate between patients with FLE and TLE prior to surgery, based on measures of verbal memory and executive functioning. Furthermore, the postoperative cognitive development was compared. Pre- and postoperative data from 109 patients with FLE and 194 patients with TLE were retrospectively analyzed. Preoperatively, there were no differences in verbal memory, and postoperatively, no distinctive cognitive change was found between patients with FLE and TLE. However, patients with FLE performed worse on a cognitive switching task. Notably, irrespective of localization, patients with a presumed epileptogenic area in the language-dominant hemisphere performed worse than patients with seizures that originated in the nonlanguage-dominant hemisphere on measures of verbal memory, both pre- and postoperatively. In sum, the results suggest that verbal memory scores may be less valuable for differentiation between TLE and FLE, while measures of executive functioning may help identify patients with FLE. Additionally, rather than the localization, epilepsy lateralization critically impacts the evaluation of verbal memory functioning in both TLE and FLE. The results are discussed in light of the current frameworks of functional disturbances in epileptic networks., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The aims of this study were to determine the rate of dysfunctional personality patterns before and after epilepsy surgery, their types, and the importance of the epileptogenic zone in a sample of people with refractory epilepsy., Methods: We conducted an ambispective observational study, including refractory epilepsy surgery candidates. Demographic, psychiatric, and neurological data were recorded. Evaluation of personality was made using the Millon Clinical Multiaxial Inventory-II (MCMI-II). Presurgical predictors of personality patterns were determined using a linear regression model. The proportion of patients with dysfunctional personality patterns, before and after surgery, was compared using the Mcnemar's test. Then a generalized estimating equation model was performed to include predictors of changes in this rate., Results: One hundred and ninety-nine participants were included. Seventy percent had a dysfunctional personality pattern before surgery. After surgery, this percentage dropped to 58%. The difference was statistically significant after adjusting for potential confounders (p = 0.013). The most common types were Cluster C personality patterns. Temporal epileptogenic zone was a significant predictor of higher scores of the Avoidant (Coef. 11.8; Confidence Interval (CI) -0.59 23.7; p = 0.051) and Compulsive (Coef. 9.55; CI 2.48 16.6; p = 0.008) personality patterns and lower scores of Histrionic (Coef. -11.4; CI -21.2 -1.55; p = 0.024) and Antisocial (Coef. -8.4; CI -15.6 -1.25; p = 0.022) personality patterns, compared to extratemporal epileptogenic zone., Conclusion: People with refractory epilepsy have high rates of dysfunctional personality patterns. These patterns differ according to the epileptogenic zone., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Surgical resection of the epileptogenic zone within the frontal lobe can be a very effective treatment for medically refractory epilepsy originating from this area. While much of the frontal lobe consists of highly eloquent tissue, surgery is not necessarily contraindicated as long as the epileptogenic zone is well-localized and the tissue resected is limited. Resection of the primary motor cortex was described by Victor Horsley in the 19th century and was used frequently in the early 20th century for a variety of neurological disorders including epilepsy; improvements in surgical techniques and mapping has led to a resurgence of its use in the past few decades. Although many surgeons are hesitant to resect tissue adjacent to the primary hand area based on fears of new motor deficits, there is extensive evidence that focal resections are well-tolerated over the long-term with residual weakness that is fairly mild: some patients experience postoperative weakness, including hemiparesis, but a stereotypical recovery of strength from proximal to distal muscles occurs over months, and only one quarter will have a permanent neurologic deficit, usually consisting of difficulty with fine motor movements. The main alternative to surgical resection is subpial transection, characterized by a small decrease in postoperative deficits and significantly worse seizure outcomes. The treatment of patients with seizures originating from this region requires a solid understanding of the structural and functional anatomy of the frontal lobe., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to report long-term seizure outcome in patients who underwent frontal lobe epilepsy (FLE) surgery., Method: This retrospective study included 44 consecutive subjects who underwent resective surgery for intractable FLE at IRCCS NEUROMED (period 2001-2014), followed up for at least 2 years (mean: 8.7 years). All patients underwent noninvasive presurgical evaluation and/or invasive electroencephalography (EEG) monitoring when nonconcordant data were obtained or epileptogenic zone was hypothesized to be close to the eloquent cortex. Electroclinical, neuroimaging, surgical data, and histology were compared to seizure outcome., Results: Mean epilepsy duration was 19 years; mean age at surgery was 31.6 years. Preoperative magnetic resonance imaging (MRI) showed a frontal lesion in 86.4 % of cases. Scalp video-electroencephalography (VEEG) monitoring detected a focal ictal onset in 90% of cases. Twenty-seven patients (61.4%) underwent invasive recordings. Resections involved dorsolateral (47.7%), medial (9%), orbital (13.6%), and rolandic (13.6%) region. Lobectomy within functional boundaries was performed in the remaining 7 cases (16%). Transient and permanent neurological deficits were observed in 2 and 3 cases, respectively. Histology revealed focal cortical dysplasia (45.5%), World Health Organization (WHO) I-II grade tumors (15.9%), gliosis (22.7%), vascular malformations (4.5%), Rasmussen encephalitis (6.8%), and normal tissue (4.5%). At last observation 68.1% of patients were in Engel's class I, 11.4% in class II, 9% in class III, and 11.4% in class IV. A favorable outcome was associated with focal ictal scalp EEG onset (p = 0.0357)., Conclusion: Surgery is a safe treatment option in drug-resistant FLE with a satisfying long-term outcome. These data highlight the importance of an appropriate selection of potential surgical candidates., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Orbitofrontal epilepsy (OFE) is less known and is poorly characterized in comparison with temporal lobe epilepsy, partly because it is rare and possibly because it is unrecognized and therefore underestimated., Objective: This paper aimed to better characterize seizure semiology, presurgical findings, and surgical outcomes in patients with OFE., Methods: We retrospectively reviewed all confidently established OFE cases from six Canadian epilepsy monitoring units between 1988 and 2014, and in the literature between 1972 and 2017. Inclusion criteria were identification of an epileptogenic lesion localized in the OFC or if the patient was seizure-free after surgical removal of the OFC in nonlesional cases., Results: Sixteen cases were identified from our databases. Fifty percent had predominantly sleep-related seizures; 56% had no aura (the remaining had nonspecific or vegetative auras), and 62.5% featured hypermotor (mostly hyperkinetic) behaviors. Interictal epileptiform discharges over frontal and temporal derivations always allowed lateralization. Magnetic resonance imaging (MRI) identified an orbitofrontal lesion in 8/16, positron emission tomography (PET) identified a hypometabolism extending outside the orbital cortex in 4/9, ictal single-photon emission computed tomography (SPECT) identified an orbital hyperperfusion in 1/5, magnetoencephalography (MEG) identified lateral orbital sources in 2/4, and intracranial electroencephalography (EEG) identified an orbitofrontal onset in 9/10. Fourteen patients underwent surgery, all reaching a favorable outcome (71.4% Engel 1; 28.6% Engel 2; mean FU=5.6years). Pre- and postoperative neuropsychological assessments revealed heterogeneous findings. Our review of literature identified 71 possible cases of OFE, 32 with confident focus localization. Extracted data from these cumulated cases supported observations made from our case series., Conclusions: Orbitofrontal epilepsy should be suspected with sleep-related, hyperkinetic seizures with no specific aura, and frontotemporal interictal discharges. Several patients have nonmotor seizures with or without auras which may resemble temporal lobe seizures. Postoperative seizure outcome was favorable, but there is inherent bias as we only included patients with a seizure-free outcome if the MRI was negative. A larger study is required to address identified gaps in knowledge such as identifying discriminative features between medial and lateral OFE, evaluating the value of more recent diagnostic tools, and assessing the neuropsychological outcome of orbital epilepsy surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to investigate the lateralizing and localizing value of ictal coprolalia and brain areas involved in its production., Methods: A retrospective search for patients manifesting ictal coprolalia was conducted in our EMU database. Continuous video-EEG recordings were reviewed, and EEG activity before and during coprolalia was analyzed using independent component analysis (ICA) technique and was compared to the seizures without coprolalia among the same patients., Results: Nine patients were evaluated (five women), eight with intracranial video-EEG recordings (icVEEG). Four had frontal or temporal lesions, and five had normal MRIs. Six patients showed impairment in the language functions and five in the frontal executive tasks. Two hundred six seizures were reviewed (60.7% from icVEEG). Ictal coprolalia occurred in 46.6% of them, always associated with limbic auras or automatisms. They arose from the nondominant hemisphere in five patients, dominant hemisphere in three, and independently from the right and left hippocampus-parahippocampus in one. Electroencephalographic activity always involved orbitofrontal and/or mesial temporal regions of the nondominant hemisphere when coprolalia occurred. Independent component analysis of 31 seizures in seven patients showed a higher number of independent components in the nondominant hippocampus-parahippocampus before and during coprolalia and in the dominant lateral temporal region in those seizures without coprolalia (p=0.009). Five patients underwent surgery, and all five had an ILAE class 1 outcome., Significance: Ictal coprolalia occurs in both males and females with temporal or orbitofrontal epilepsy and has a limited lateralizing value to the nondominant hemisphere but can be triggered by seizures from either hemisphere. It involves activation of the paralimbic temporal-orbitofrontal network., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In order to determine the anatomical neural network underlying ictal pouting (IP), with the mouth turned down like a "chapeau de gendarme", in frontal lobe epilepsy (FLE), we reviewed the video-EEG recordings of 36 patients with FLE who became seizure-free after surgery. We selected the cases presenting IP, defined as a symmetrical and sustained (>5s) lowering of labial commissures with contraction of chin, mimicking an expression of fear, disgust, or menace. Ictal pouting was identified in 11 patients (8 males; 16-48 years old). We analyzed the clinical semiology, imaging, and electrophysiological data associated with IP, including FDG-PET in 10 and SEEG in 9 cases. In 37 analyzed seizures (2-7/patient), IP was an early symptom, occurring during the first 10s in 9 cases. The main associated features consisted of fear, anguish, vegetative disturbances, behavioral disorders (sudden agitation, insults, and fighting), tonic posturing, and complex motor activities. The epileptogenic zone assessed by SEEG involved the mesial frontal areas, especially the anterior cingulate cortex (ACC) in 8 patients, whereas lateral frontal onset with an early spread to the ACC was seen in the other patient. Ictal pouting associated with emotional changes and hypermotor behavior had high localizing value for rostroventral "affective" ACC, whereas less intense facial expressions were related to the dorsal "cognitive" ACC. Fluorodeoxyglucose positron emission tomography demonstrated the involvement of both the ACC and lateral cortex including the anterior insula in all cases. We propose that IP is sustained by reciprocal mesial and lateral frontal interactions involved in emotional and cognitive processes, in which the ACC plays a pivotal role., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Few studies have focused on language changes following frontal lobe epilepsy (FLE) surgery. The aim of the current study is to quantify the role of resection location and size in verbal fluency decline after FLE surgery and to examine its predictors. A retrospective chart review identified 36 adult patients who underwent FLE surgery. Verbal fluency was assessed using the Controlled Oral Word Association Test (COWAT). Nine (25%) of the patients had significant decline. Binary logistic regression incorporating side of resection and preoperative COWAT score significantly predicted decline and accounted for 25% of the variance. A trend was also noted for decliners to have higher postoperative seizure recurrence (p=0.067). There was no effect of size of resection. Patients undergoing FLE surgery are at risk of verbal fluency decline, especially if they have a high presurgical verbal fluency score, undergo a frontal lobe resection in the language dominant hemisphere, and have poor seizure outcome., (Copyright © 2013 Elsevier Inc. All rights reserved.)

This study aimed at investigating psychological features before and two years after epilepsy surgery. Fifty patients, 39 with temporal lobe epilepsy (TLE) and 11 with frontal lobe epilepsy (FLE), were assessed at baseline and two years postoperatively with the Karolinska Scales of Personality (KSP). Baseline group level outcome was normal while individual level analyses delineated some mild to moderate degrees of psychological problems exceeding the normal range in subsets of patients. Features of hostility characterized half of the FLE and one-fourth of the TLE patients. Above 1/3 in each group had dependency features. About 1/3 of the TLE patients suffered from psychasthenia. In conclusion, even though group levels were normal, several patients had psychological problems. The main longitudinal result was that the personality features were stable and did not change after epilepsy surgery., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Recent research has pointed to the possibility of a bidirectional relationship between seizure frequency in epilepsy and depressive symptoms. The study described here investigated the relationship between preoperative depressive symptomatology and postoperative seizure outcome in a sample of patients with temporal (TLE) and frontal (FLE) lobe epilepsy., Methods: A retrospective analysis was conducted on the data from 115 eligible patients with TLE (N=97) and FLE (N=18) and resections limited to one cortical lobe who were evaluated preoperatively and 1year after epilepsy surgery with respect to depressive symptoms (Beck Depression Inventory, BDI) and seizure outcome. The latter was assessed in terms of actual total seizure frequency as well as a dichotomous variable (seizure free vs. not seizure free) for the 1-year outcome. Repeated-measures analyses of variance and regression analyses were applied., Results: Seizure-free patients had significantly lower BDI scores preoperatively as well as postoperatively than patients who were not seizure free. In the regression analyses, the preoperative BDI score was a significant predictor of postoperative seizure frequency as well as seizure freedom. When only patients with TLE were analyzed, the results for the association between preoperative BDI and postoperative seizure frequency and seizure freedom remained consistent., Conclusion: The present results provide evidence for a statistical bidirectionality of the relationship between depressive symptoms and postoperative seizure status in a mixed sample of patients with TLE and FLE. Possible reasons for this bidirectional association include an underlying common pathology in both depression and epilepsy, for example, structural changes or functional alterations in neurotransmitter systems.

Frontal lobe epilepsy (FLE) is a seizure disorder with a lower prevalence than temporal lobe epilepsy (TLE). Despite its consequences on cognitive and emotional well-being, the neuropsychology of FLE has not been well studied. By contrast, TLE has been studied meticulously, leading to a relevant understanding of memory and the functional characteristics of the temporal and limbic circuits. The neuropsychological studies on FLE report deficits in motor coordination and planning, reduced attention span, and difficulties in response inhibition in complex cognitive tasks. This review aims to illustrate the most relevant neurocognitive dimensions, psychiatric comorbidity, and postoperative neuropsychological outcome of FLE. Methodological suggestions for future research are also included by critically reviewing the existing literature.

Despite being a common sign in focal epilepsies, the exact symptomatogenic zone for oroalimentary automatisms remains largely unknown. We describe a patient with refractory complex partial seizures secondary to a right temporoparietal malformation of cortical development who underwent prolonged video/EEG monitoring with subdural electrodes. During his typical seizures, the patient manifested decreased awareness but never automatisms. However, during electrical cortical stimulation of two electrodes located over the right inferior frontal gyrus, oroalimentary automatisms with preserved consciousness were elicited, with no afterdischarges detected in the adjacent electrodes. These two electrodes were distant from the seizure onset zone and were not involved in seizure propagation. This case provides evidence that fronto-opercular cortex may be involved in the generation of oroalimentary automatisms.

Human social behavior depends on a set of perceptive, mnemonic, and interpretive abilities that together may be termed social cognition. Lesion and functional imaging studies of social cognitive functions implicate the temporal lobes (in particular, the nondominant temporal lobe) and mesial temporal structures as critical at the front end of social cognitive processes. The frontal lobes, in turn, function to interpret and to modulate these processes via top-down control. Damage to frontal regions is associated with specific derangements in social behavior. Chronic focal-onset epilepsy and its surgical treatment commonly affect these neuroanatomic regions and might therefore impact social function. Postoperative social function helps determine quality of life for both patients and families. There is some evidence that resective seizure surgery affects social cognition, but there are significant weaknesses in our current knowledge that can be overcome with comprehensive longitudinal research.

To verify whether interictal noninvasive information detected by magnetoencephalography (MEG) recordings can contribute to localize focal epileptic activity relevant for seizure generation in lesional frontal lobe epilepsy, magnetic source imaging (MSI) localizations of epileptic discharges were compared to the extent of neurosurgical resection and postoperative outcome. Preoperative MEG spike localizations were displayed in postoperative magnetic resonance imaging (MRI) scans to check whether dipole sites were located within the resection cavity. Moreover, MEG localizations were compared with results of prolonged video-EEG monitoring and, in three cases, with invasive EEG recordings. Our results in five cases with lesional frontal lobe epilepsy showed that good surgical outcome could be achieved in those patients where the majority of MEG spike localizations were located within the resected brain volume.

The purpose of this study was to compare language function in children undergoing temporal or frontal lobe surgery to control intractable epilepsy. Language measures (expressive vocabulary, receptive vocabulary, comprehension, reading, spelling, phonemic fluency, and category fluency) were administered to 9 children with frontal lobe epilepsy (mean age: 10.8 +/- 2.7 years) and 10 children with temporal lobe epilepsy (11.5 +/- 2.6 years). The results indicate that no differences exist, in language function, before and after surgery between children with frontal and temporal lobe epilepsy (all p > or = .05). Children with left hemisphere lesions had significantly lower scores than those with right on category fluency and comprehension, but laterality effects were not seen on the other measures. In both groups, language function was not significantly affected by surgery.

NR1 and NR2 are the two gene families for the NMDA receptor. In vitro studies show that while NR2 alone is nonfunctional, NR1 alone produces weak currents to glutamate or NMDA. We previously showed by immunocytochemistry (ICC) that in normal appearing, nonepileptic human cortical neurons, only NR1 and not NR2 proteins were expressed, in contrast to the presence of both NR1 and NR2 in normal rat cortical neurons. We also showed, in dysplastic epileptic cortex, that both NR1 and NR2 were highly expressed using ICC on adjacent 30-microm sections. However, the relative coexpressions of NR1 and NR2 proteins in single neurons in single sections of human epileptic cortex were unknown. In this study, we used double-labeled immunofluorescence and confocal microscopy to examine the distribution and coexpression of subunit proteins for NR1 and NR2A/B in both nondysplastic (control comparison) and dysplastic regions of human brain resected for the treatment of intractable epilepsy (11 patients). In nondysplastic regions, cortical neurons did not have immunoreactivity (ir) for NR2A/B, whereas NR1-ir was abundant. By contrast, dysplastic neurons in the regions with epileptic cortical dysplasia showed intense NR2A/B-ir in the somata and their dendritic processes. These same NR2A/B-ir dysplastic neurons were colabeled by NR1. These results demonstrate directly that dysplastic neurons express both NR2A/B and NR1 proteins, whereas nondysplastic cortical neurons express only NR1 proteins. Selective coexpression of NR2A/B and NR1 in dysplastic neurons suggests that NR2A/B may form heteromeric NR1-NR2 coassemblies and hyperexcitability in dysplastic neurons that could contribute to focal seizure onset., (Copyright 1999 Academic Press.)