Gelastic seizures associated with hypothalamic hamartomas. An update in the clinical presentation,diagnosis and treatment

Gelastic seizures are epileptic events characterized by bouts of laughter. Laughter-like vocalization is usually combined with facial contraction in the form of a smile. Autonomic features such as flushing, tachycardia, and altered respiration are widely recognized. Conscious state may not be impaired, although this is often difficult to asses particularly in young children. Gelastic seizures have been associated classically to hypothalamic hamartomas, although different extrahypothalamic localizations have been described. Hypothalamic hamartomas are rare congenital lesions presenting with the classic triad of gelastic epilepsy, precocious puberty and developmental delay. The clinical course of patients with gelastic seizures associated with hypothalamic hamartomas is progressive, commencing with gelastic seizures in infancy, deteriorating into more complex seizure disorder resulting in intractable epilepsy. Electrophysiological, radiological, and pathophysiological studies have confirmed the intrinsic epileptogenicity of the hypothalamic hamartoma. Currently the most effective surgical approach is the trancallosal anterior interforniceal approach, however newer approaches including the endoscopic and other treatment such as radiosurgery and gamma knife have been used with success. This review focuses on the syndrome of gelastic seizures associated with hypothalamic hamartomas, but it also reviews other concepts such as status gelasticus and some aspects of gelastic seizures in other locations.     

Surgical treatment of extra‐hypothalamic epilepsies presenting with gelastic seizures

We provide an overview of the surgical outcome of extra‐hypothalamic epilepsies with gelastic seizures based on an original case report and a summary of the literature. Twenty‐two articles providing information on the outcome of resective surgery in 39 patients with extra‐hypothalamic gelastic seizures from the temporal (19 patients) or frontal lobe (20 patients) were selected. We add another case of temporal lobe gelastic seizures to the literature with a video demonstrating the mirthful component of this patient's laughing seizures. Drug‐refractory cases of gelastic seizures from the temporal or frontal lobes are amenable to surgical treatment following thorough investigation with imaging, as well as scalp and intracranial EEG.     

Prefrontal cortex afferents to the anterior temporal lobe in the Macaca fascicularis monkey

The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked to cognitive processes. The ATL includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices. Multiple sensory modalities converge in the ATL. All of them (except the rostral inferotemporal and superior temporal gyrus cortices) are components of the medial temporal lobe, which is critical for long‐term memory processing. We studied the LPFC connections with the ATL by placing retrograde tracer injections into the ATL: the temporal polar (n = 3), perirhinal (areas 35 and 36, n = 6), and inferotemporal cortices (area TE, n = 5), plus one additional deposit in the posterior parahippocampal cortex (area TF, n = 1). Anterograde tracer deposits into the dLPFC (A9 and A46, n = 2), the vLPFC (A46v, n = 2), and the orbitofrontal cortex (OF; n = 2) were placed for confirmation of those projections. The results showed that the vLPFC displays a moderate projection to rostral area TE and the dorsomedial portion of the temporal polar cortex; in contrast, the dLPFC connections with the ATL were weak. By comparison, the OFC and medial frontal cortices (MFC) showed dense connectivity with the ATL, namely, A13 with the temporopolar and perirhinal cortices. All areas of the MFC projected to the temporopolar cortex, albeit with a lower intensity. The functional significance of such paucity of LPFC afferents is unknown. J. Comp. Neurol. 523:2570–2598, 2015. © 2015 Wiley Periodicals, Inc.     

Epilepsy surgery in children with seizures arising from the rolandic cortex

Purpose: Medically intractable seizures arising from the sensorimotor (rolandic) cortex present a formidable challenge for epileptologists and epilepsy surgeons. The objective of this study was to evaluate the safety and efficacy of surgical treatment for seizures in this region. Methods: We retrospectively reviewed the medical records of 24 children and adolescents who underwent surgical management of refractory rolandic epilepsy at our institution. Results: Patient age at the time of surgery ranged between 1.9 and 19.2 years, and median postoperative follow‐up was 2.3 years. Three patients had clear lesions on preoperative magnetic resonance imaging (MRI) that correlated with noninvasive electroencephalography (EEG) and underwent single‐stage lesionectomies. Of the 21 patients who underwent invasive monitoring, 19 underwent therapeutic procedures, including lesionectomy, topectomy, and multiple subpial transections. Engel class I and II outcomes were seen in five of six patients (84.0%) after lesionectomy and in seven of nine patients (77.0%) and four of six patients (66.7%) after sensorimotor corticectomy or multiple subpial transections (MSTs), respectively. At last follow‐up, neurologic deficits were observed following 50.0% (n = 3 of 6) of lesionectomies and 67.0% (n = 7 of 9) of topectomies; no neurologic deficits were seen in patients undergoing motor cortex MSTs. No correlation existed between seizure outcome and duration of epilepsy, age at diagnosis, age at surgery, histopathology, or the presence or absence of a discrete lesion. Discussion: Surgery for appropriately selected children with intractable seizures arising from rolandic cortex was effective and associated with minimal neurologic morbidity in many cases. Engel I–II outcome was achieved in 77% of patients overall, and neurologic deficits were often mild and improved over time. Lesionectomy resulted in the best seizure control, followed by topectomy, and then MSTs.     

The prefrontal substrate of reflexive saccade inhibition in humans.

BACKGROUND: Prefrontal dysfunction in neuropsychiatric disorders such as schizophrenia has been shown to impair inhibition of reflexive saccadic eye movements; however, it is unclear whether reflexive saccade inhibition can be attributed to a distinct subregion of the human prefrontal cortex. METHODS: We tested 15 patients with acute unilateral ischemic lesions of the prefrontal cortex and 20 control subjects with an antisaccade task. Lesions were reconstructed using Talairach coordinates, and possible candidate regions for reflexive saccade inhibition were identified. RESULTS: Significantly increased antisaccade error rates were observed in patients with lesions affecting a region in mid-dorsolateral prefrontal cortex or the white matter between this region and the anterior portions of the internal capsule. Antisaccade error rates of patients with lesions outside this region were normal. These findings were largely independent of lesion volume, postlesion delay, and subject age. CONCLUSIONS: Our findings suggest that inhibition of reflexive saccades depends on a circumscribed subregion of the human dorsolateral prefrontal cortex. This region closely corresponds to Brodmann area 46 as defined by recent cytoarchitectonic studies. Increased antisaccade error rates in patients with prefrontal pathology may be explained by dysfunction of this region.     

Comparison of differential neuronal responsiveness for different regions of the prefrontal cortex in a conditional visual discrimination task

To investigate neuronal processing during monkeys' performance of a visual conditional discrimination task, recordings were made from four areas of prefrontal cortex (ventromedial, orbitofrontal, dorsolateral and anterior cingulate) where lesions have been shown to produce impairment of such tasks. Of 1911 recorded neurons, 573 (31%) responded to elements of the task. This proportion was less than the 50% previously reported as responsive in temporal cortex under the same conditions, suggesting sparser encoding in prefrontal than temporal cortex. Of the responsive prefrontal neurons, 165 (29%) responded differently on the different types of trial, so signalling various types of information relevant to task performance and cognition. In line with recent lesion findings, in the dorsolateral region the incidence of such differentially responsive neurons was only an eighth that in the other regions. The relatively high incidence of neuronal responses that encoded a potential instruction cue rather than specific individual stimulus arrangements was consistent with the animals solving the task by using such information, though other neuronal responses could have enabled the task to have been solved by rote learning. Compared to temporal neurons, prefrontal responses more frequently coded information relating to the planned behavioural response rather than perceptual aspects of the task. Population differential response latencies were long (> approximately 225 ms) in prefrontal cortex. A comparison of such differential latencies between temporal and prefrontal cortex indicated that potential information flow was likely to be primarily from temporal to prefrontal cortex rather than vice versa.     

Flexible spatial learning requires both the dorsal and ventral hippocampus and their functional interactions with the prefrontal cortex

When faced with changing contingencies, animals can use memory to flexibly guide actions, engaging both frontal and temporal lobe brain structures. Damage to the hippocampus (HPC) impairs episodic memory, and damage to the prefrontal cortex (PFC) impairs cognitive flexibility, but the circuit mechanisms by which these areas support flexible memory processing remain unclear. The present study investigated these mechanisms by temporarily inactivating the medial PFC (mPFC), the dorsal HPC (dHPC), and the ventral HPC (vHPC), individually and in combination, as rats learned spatial discriminations and reversals in a plus maze. Bilateral inactivation of either the dHPC or vHPC profoundly impaired spatial learning and memory, whereas bilateral mPFC inactivation primarily impaired reversal versus discrimination learning. Inactivation of unilateral mPFC together with the contralateral dHPC or vHPC impaired spatial discrimination and reversal learning, whereas ipsilateral inactivation did not. Flexible spatial learning thus depends on both the dHPC and vHPC and their functional interactions with the mPFC.     

Changes in midline thalamic recruiting responses in the prefrontal cortex of the rat during the development of chronic limbic seizures

Purpose:   Mesial temporal lobe epilepsy (MTLE) is a common form of epilepsy that affects the limbic system and is associated with decreases in memory and cognitive performance. The medial prefrontal cortex (PC) in rats, which has a role in memory, is associated with and linked anatomically to the limbic system, but it is unknown if and how MTLE affects the PC.
Methods:   We evoked responses in vivo in the PC by electrical stimulation of the mediodorsal (MD) and reuniens (RE) nuclei of the thalamus at several time points following status epilepticus, before and after onset of spontaneous seizures. Kindled animals were used as additional controls for the effect of seizures that were independent of epilepsy.
Results:   Epileptic animals had decreased response amplitudes and significantly reduced recruiting compared to controls, whereas kindled animals showed an increase in both measures. These changes were not associated with neuronal loss in the PC, although there was significant loss in both the MD and RE in the epileptic animals.
Conclusions:   There is a significant reduction in the thalamically induced evoked responses in the PCs of epileptic animals. This finding suggests that physiologic dysfunction in MTLE extends beyond primary limbic circuits into areas without overt neuronal injury.     

Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging.

OBJECTIVES: Gray and white matter volume deficits have been reported in a number of studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural magnetic resonance imaging (MRI) studies of adults with ADHD. This structural MRI study used an a priori region of interest approach. METHODS: Twenty-four adults with DSM-IV ADHD and 18 healthy controls comparable on age, socioeconomic status, sex, handedness, education, IQ, and achievement test performance had an MRI on a 1.5T Siemens scanner. Cortical and sub-cortical gray and white matter were segmented. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere. Based on a priori hypotheses we focused on prefrontal, anterior cingulate cortex (ACC) and overall gray matter volumes. General linear analyses of the volumes of brain regions, adjusting for age, sex, and total cerebral volumes, were used to compare groups. RESULTS: Relative to controls, ADHD adults had significantly smaller overall cortical gray matter, prefrontal and ACC volumes. CONCLUSIONS: Adults with ADHD have volume differences in brain regions in areas involved in attention and executive control. These data, largely consistent with studies of children, support the idea that adults with ADHD have a valid disorder with persistent biological features.     

Distinct regions of medial rostral prefrontal cortex supporting social and nonsocial functions

While some recent neuroimaging studies have implicated medialrostral prefrontal cortex (MPFC) in ‘mentalizing’and self-reflection, others have implicated this region in attentiontowards perceptual vs self-generated information. In order toreconcile these seemingly contradictory findings, we used fMRIto investigate MPFC activity related to these two functionsin a factorial design. Participants performed two separate tasks,each of which alternated between ‘stimulus-oriented phases’(SO), where participants attended to task-relevant perceptualinformation, and ‘stimulus-independent phases’ (SI),where participants performed the same tasks in the absence ofsuch information. In half of the blocks (‘mentalizingcondition’), participants were instructed that they wereperforming these tasks in collaboration with an experimenter;in other blocks (‘non-mentalizing condition’), participantswere instructed that the experimenter was not involved. In fact,the tasks were identical in these conditions. Neuroimaging datarevealed adjacent but clearly distinct regions of activationwithin MPFC related to (i) mentalizing vs non-mentalizing conditions(relatively caudal/superior) and (ii) SO vs SI attention (relativelyrostral/inferior). These results generalized from one task tothe other, suggesting a new axis of functional organizationwithin MPFC.     

Differential connections of the perirhinal and parahippocampal cortex with the orbital and medial prefrontal networks in macaque monkeys

Previous anatomical studies indicate that the orbital and medial prefrontal cortex (OMPFC) of monkeys is organized into an "orbital" network, which appears to be related to feeding and reward, and a "medial" network, related to visceral control and emotion. In this study, we examined the connections of the orbital and medial prefrontal networks with the perirhinal (areas 35 and 36) and parahippocampal (areas TF and TH) cortex with anterograde and retrograde axonal tracers. The perirhinal cortex is reciprocally connected with orbital network areas Iapm, Iam, Ial, 13m, 13l, 12r, and 11l. In contrast, the parahippocampal cortex is reciprocally connected with the medial network, especially areas around the corpus callosum (areas 24a/b, caudal 32, and 25), and with area 11m. Projections from the parahippocampal cortex also extend to areas 10m, 10o, Iai, and rostral area 32, as well as to dorsolateral areas 9 and 46. In addition, both the perirhinal and parahippocampal cortex are reciprocally connected with areas that are intermediate between the orbital and medial networks (areas 13a, 13b, and 14c) and with the supracallosal area 24a'/b'. Outside the frontal cortex, the perirhinal cortex and the orbital prefrontal network are both interconnected with the ventral part of the temporal pole (TG), area TE and the ventral bank and fundus of the superior temporal sulcus (STS), and the dysgranular insula. In contrast, the parahippocampal cortex and the medial prefrontal network are connected with the dorsal TG, the rostral superior temporal gyrus (STG) and dorsal bank of STS, and the retrosplenial cortex.     

Psychopathology and working memory-induced activation of the prefrontal cortex in schizophrenia-like psychosis of epilepsy: Evidence from magnetoencephalography

Aim: The aim of this study was to investigate whether magnetoencephalographic oscillations underlying working memory dysfunction in the dorsolateral prefrontal cortex (DLPFC) are related to psychopathological disturbance in patients with schizophrenia‐like psychosis of epilepsy (SLPE). Methods: Twelve patients with SLPE and 14 non‐psychotic epilepsy controls participated in this study. Magnetoencephalography was recorded while patients performed a visual working memory (WM) task. Psychopathology was assessed using a four‐factor structure of the Brief Psychiatric Rating Scale, and regression analyses were carried out to examine the relative impact of severity of psychopathology on WM‐induced activation of the DLPFC. Results: We found that activation of the WM‐compromising DLPFC, as indicated by increased alpha desynchronization in patients with SLPE compared with their non‐psychotic counterparts, showed a positive linear correlation with disorganization symptom scores. This association remained significant after controlling for confounding factors, including age, task performance, IQ, and duration of psychosis. Conclusion: Our results indicate that abnormal activation in prefrontal areas engaged during working memory may be critical to domains of psychopathology, in particular disorganized thought‐processing in patients with SLPE.     

Anatomical segmentation of the human medial prefrontal cortex

The medial prefrontal areas 32, 24, 14, and 25 (mPFC) form part of the limbic memory system, but little is known about their functional specialization in humans. To add anatomical precision to structural and functional magnetic resonance imaging (MRI) data, we aimed to identify these mPFC subareas in histological preparations of human brain tissue, determine sulci most consistently related with mPFC areal boundaries, and use these sulci to delineate mPFC areas in MRIs. To achieve this, we obtained three‐dimensional MRI data from 11 ex vivo hemispheres and processed them for cyto‐ and myelo‐architectonic analysis. The architectonic boundaries of mPFC areas were identified in histology and cortical surface length and volumes were measured. Unfolded maps of histologically determined boundaries were generated to identify the association of mPFC areal boundaries with sulci across cases. This analysis showed that cingulate and superior rostral were the sulci most consistently related to mPFC areal boundaries. Based on presence/absence and anastomosis between such sulci, 6 sulci patterns in the 11 hemispheres were found. A further analysis of 102 hemispheres of in vivo MRI scans (N = 51 males, mean ± SD 24.1 ± 3.1 years of age) showed similar sulci patterns, which allowed us to delineate the mFPC areas in them. The volumes of mPFC areas across histological, ex vivo and in vivo MRI delineations were comparable and probabilistic maps generated from the MRIs of the102 hemispheres. Probabilistic maps of mPFC areas were registered to MNI space and are available for regional analysis of functional magnetic resonance imaging data.     

On the involvement of prefrontal networks in cognitive ageing

Normal ageing is associated with a wide variety of disturbances in the structure and function of the human brain. Recent neuroimaging studies suggest that the prefrontal cortex (PFC) is particularly vulnerable to the effects of ageing. These findings are compatible with the so-called ‘frontal ageing hypothesis' which has been formulated on the basis of neuropsychological research on non-pathological ageing. We will argue on the basis of recent structural and functional neuroimaging studies that this hypothesis needs to be refined, especially to acknowledge the possible relevance of a distinction between subregions within the PFC. In addition, findings with regard to a differential involvement of grey versus white matter suggest that both have to be considered in relation to age- related cognitive decline. Hence, neural networks and larger systems of interconnected brain regions and the functional activity in these circuits may be more important than specific cortical regions to explain age effects on cognitive functioning. Finally, it is important to consider individual variability due to sex differences and age-extrinsic biomedical factors in research which examines the relationship between brain structure or function and cognitive ageing.     

Gamma knife radiosurgery for the treatment of recurrent seizures after incomplete anterior temporal lobectomy

To evaluate the efficacy and safety of gamma knife radiosurgery (GKS) in treating temporal lobe epilepsy, GKS was performed in four adult patients with recurrent complex partial seizures who underwent incomplete anterior temporal lobectomy (ATL) but were reluctant to undergo a second resective surgery. A marginal dose of 24.5–25 Gy, corresponding to 65–70% isodose curve, was delivered to the treatment target that included the residual amygdala and the head and anterior body of the hippocampus.None of the patients had severe acute side effects but three patients had radiation-induced MRI signal changes around the target volume 13, 20, and 24 months after GKS, respectively. All four patients had significant seizure reduction during the first 6-month period and clinical efficacy persisted throughout the 2-year follow-up period. All of the patients also had improved neuropsychological profiles, including memory function and quality-of-life, compared to their pre-GKS conditions.In conclusion, the safety and clinical efficacy of GKS make it a reasonable and suitable therapeutic alternative for patients with recurrent seizures after incomplete ATL. A higher marginal dose of >25 Gy and wider coverage may be more clinically beneficial but warrant further investigation.     

Psychomotor seizures, Penfield, Gibbs, Bailey and the development of anterior temporal lobectomy: A historical vignette

Psychomotor seizures, referred to as limbic or partial complex seizures, have had an interesting evolution in diagnosis and treatment. Hughlings Jackson was the first to clearly relate the clinical syndrome and likely etiology to lesions in the uncinate region of the medial temporal lobe. With the application of electroencephalography (EEG) to the study of human epilepsy as early as 1934 by Gibbs, Lennox, and Davis in Boston, electrical recordings have significantly advanced the study of epilepsy. In 1937, Gibbs and Lennox proposed the term "psychomotor epilepsy" to describe a characteristic EEG pattern of seizures accompanied by mental, emotional, motor, and autonomic phenomena. Concurrently, typical psychomotor auras and dreamy states were produced by electrical stimulation of medial temporal structures during epilepsy surgery by Penfield in Montreal. In 1937, Jasper joined Penfield, EEG was introduced and negative surgical explorations became less frequent. Nevertheless, Penfield preferred to operate only on space occupying lesions. A milestone in psychomotor seizure diagnosis was in the year 1946 when Gibbs, at the Illinois Neuropsychiatric Institute, Chicago, reported that the patient falling asleep during EEG was a major activator of the psychomotor discharges and electrographic ictal episodes becoming more prominently recorded. Working with Percival Bailey, Gibbs was proactive in applying EEG to define surgical excision of the focus in patients with intractable psychomotor seizures. By early 1950s, the Montreal group began to clearly delineate causative medial temporal lesions such as hippocampal sclerosis and tumors in the production of psychomotor seizures.     

A new subdivision of anterior piriform cortex and associated deep nucleus with novel features of interest for olfaction and epilepsy

The anterior part of the piriform cortex (the APC) has been the focus of cortical-level studies of olfactory coding and associative processes and has attracted considerable attention as a result of a unique capacity to initiate generalized tonic-clonic seizures. Based on analysis of cytoarchitecture, connections, and immunocytochemical markers, a new subdivision of the APC and an associated deep nucleus are distinguished in the rat. As a result of its ventrorostral location in the APC, the new subdivision is termed the APC(VR). The deep nucleus is termed the pre-endopiriform nucleus (pEn) based on location and certain parallels to the endopiriform nucleus. The APC(VR) has unique features of interest for normal function: immunostaining suggests that it receives input from tufted cells in the olfactory bulb in addition to mitral cells, and it provides a heavy, rather selective projection from the piriform cortex to the ventrolateral orbital cortex (VLO), a prefrontal area where chemosensory, visual, and spatial information converges. The APC(VR) also has di- and tri-synaptic projections to the VLO via the pEn and the submedial thalamic nucleus. The pEn is of particular interest from a pathological standpoint because it corresponds in location to the physiologically defined "deep piriform cortex" ("area tempestas") from which convulsants initiate temporal lobe seizures, and blockade reduces ischemic damage to the hippocampus. Immunostaining revealed novel features of the pEn and APC(VR) that could alter excitability, including a near-absence of gamma-aminobutyric acid (GABA)ergic "cartridge" endings on axon initial segments, few cholecystokinin (CCK)-positive basket cells, and very low gamma-aminobutyric acid transporter-1 (GAT1)-like immunoreactivity. Normal functions of the APC(VR)-pEn may require a shaping of neuronal activity by inhibitory processes in a fashion that renders this region susceptible to pathological behavior.     

Hippocampal neurodegeneration, spontaneous seizures, and mossy fiber sprouting in the F344 rat model of temporal lobe epilepsy

The links among the extent of hippocampal neurodegeneration, the frequency of spontaneous recurrent motor seizures (SRMS), and the degree of aberrant mossy fiber sprouting (MFS) in temporal lobe epilepsy (TLE) are a subject of contention because of variable findings in different animal models and human studies. To understand these issues further, we quantified these parameters at 3-5 months after graded injections of low doses of kainic acid (KA) in adult F344 rats. KA was administered every 1 hr for 4 hr, for a cumulative dose of 10.5 mg/kg bw, to induce continuous stages III-V motor seizures for >3 hr. At 4 days post-KA, the majority of rats (77%) exhibited moderate bilateral neurodegeneration in different regions of the hippocampus; however, 23% of rats exhibited massive neurodegeneration in all hippocampal regions. All KA-treated rats displayed robust SRMS at 3 months post-KA, and the severity of SRMS increased over time. Analyses of surviving neurons at 5 months post-KA revealed two subgroups of rats, one with moderate hippocampal injury (HI; 55% of rats) and another with widespread HI (45%). Rats with widespread HI exhibited greater loss of CA3 pyramidal neurons and robust aberrant MFS than rats with moderate HI. However, the frequency of SRMS (approximately 3/hr) was comparable between rats with moderate and widespread HI. Thus, in comparison with TLE model using Sprague-Dawley rats (Hellier et al. [1998] Epilepsy Res. 31:73-84), a much lower cumulative dose of KA leads to robust chronic epilepsy in F344 rats. Furthermore, the occurrence of SRMS in this model is always associated with considerable bilateral hippocampal neurodegeneration and aberrant MFS. However, more extensive hippocampal CA3 cell loss and aberrant MFS do not appear to increase the frequency of SRMS. Because most of the features are consistent with mesial TLE in humans, the F344 model appears ideal for testing the efficacy of potential treatment strategies for mesial TLE.     

High susceptibility of the anterior and posterior piriform cortex to induction of convulsions by bicuculline

Accumulating evidence suggests that the piriform cortex (PC) plays a critical role in the development of limbic motor seizures. In the anterior piriform cortex (aPC), a functionally defined, discrete epileptogenic site has been previously identified by unilateral microinjection of bicuculline in Sprague-Dawley (SD) rats and termed the 'area tempestas' (AT). Compared to this site in the aPC, more posterior PC sites, particularly a site in the transition zone between the posterior and aPC (central PC) exhibited a greater susceptibility to electrical stimulation. However, it is not known whether central and posterior sites in the PC differ from the aPC, including the AT, with regard to their sensitivity to bicuculline. In the present study, unilateral focal microinfusion of picomole quantities of bicuculline induced behavioural (focal and generalized) seizures in deep layers of all parts of the PC in two rat strains, Wistar and SD. The incidence of generalized seizures was higher in the AT of SD rats, but no such difference was seen in Wistar rats, arguing against the previous proposal that the rat AT is unique in its sensitivity to induction of seizures by bicuculline compared to other locations within or outside of the PC. Injection of biotin-dextran in PC seizure-sensitive sites in SD rats showed clear differences in anterograde and retrograde labelling between the different PC sites. Therefore, although it was possible to evoke generalized seizures from all parts of the PC, the anatomical connections of the bicuculline injection sites were qualitatively different. The results suggest that the deep layers of the entire PC are highly sensitive to seizure induction by bicuculline, thus substantiating the notion that the PC may be important in seizure generation and propagation.