Heterotopic Cortex Research Articles

Reduced expression of perineuronal nets in the normotopic somatosensory cortex of the tish rat

The tish (telencephalic internal structural heterotopia) rat is a naturally occurring and unique model of a malformation of cortical development (MCD) arising from a sponeantous mutation in the Eml1 gene. Tish rats are characterized by a macroscopic bilateral heterotopic dysplastic cortex (HDCx) and an overlaying, intact normotopic neocortex (NNCx). These two cortices are functional and have been reported to innervate and establish connections with subcortical regions including the thalamus, resulting in a dual-cortical representation. Additionally, impaired GABAergic neurotransmission and early-onset spike wave discharge bursts have been reported in developing tish rats. Perineuronal nets (PNNs) are specialized extraceullar matrix structures that predominately surround and stabilize parvalbumin-positive (PV+) GABAergic interneurons and are essential components of the neural landscape. Here, we report a significant reduction in the average number of WFA+-PNNs in the normotopic somatosensory cortex (NSSCx) of the tish rat at two developmental time points, P16 and P35, corresponding to a decrease in the number of PV+ interneurons ensheathed by a PNN in the NSSCx. Compared with control animals, PNN expression was partially, but significantly restored following treatment with insulin-like growth factor 1 (IGF-1). These data suggest that the ‘dual cortical representation’ in the setting of an MCD reduces the cortical activation necessary for proper PNN expression likely contributing to the impairments in GABAergic neurotransmission and network excitability previously identified in the tish rat.

A deletion in Eml1 leads to bilateral subcortical heterotopia in the tish rat

Children with malformations of cortical development (MCD) are at risk for epilepsy, developmental delays, behavioral disorders, and intellectual disabilities. For a subset of these children, antiseizure medications or epilepsy surgery may result in seizure freedom. However, there are limited options for treating or curing the other conditions, and epilepsy surgery is not an option in all cases of pharmacoresistant epilepsy. Understanding the genetic and neurobiological mechanisms underlying MCD is a necessary step in elucidating novel therapeutic targets. The tish (telencephalic internal structural heterotopia) rat is a unique model of MCD with spontaneous seizures, but the underlying genetic mutation(s) have remained unknown. DNA and RNA-sequencing revealed that a deletion encompassing a previously unannotated first exon markedly diminished Eml1 transcript and protein abundance in the tish brain. Developmental electrographic characterization of the tish rat revealed early-onset of spontaneous spike-wave discharge (SWD) bursts beginning at postnatal day (P) 17. A dihybrid cross demonstrated that the mutant Eml1 allele segregates with the observed dysplastic cortex and the early-onset SWD bursts in monogenic autosomal recessive frequencies. Our data link the development of the bilateral, heterotopic dysplastic cortex of the tish rat to a deletion in Eml1.

Mutations in the Heterotopia Gene Eml1/EML1 Severely Disrupt the Formation of Primary Cilia

Apical radial glia (aRGs) are predominant progenitors during corticogenesis. Perturbing their function leads to cortical malformations, including subcortical heterotopia (SH), characterized by the presence of neurons below the cortex. EML1/Eml1 mutations lead to SH in patients, as well as to heterotopic cortex (HeCo) mutant mice. In HeCo mice, some aRGs are abnormally positioned away from the ventricular zone (VZ). Thus, unraveling EML1/Eml1 function will clarify mechanisms maintaining aRGs in the VZ. We pinpoint an unknown EML1/Eml1 function in primary cilium formation. In HeCo aRGs, cilia are shorter, less numerous, and often found aberrantly oriented within vesicles. Patient fibroblasts and human cortical progenitors show similar defects. EML1 interacts with RPGRIP1L, a ciliary protein, and RPGRIP1L mutations were revealed in a heterotopia patient. We also identify Golgi apparatus abnormalities in EML1/Eml1 mutant cells, potentially upstream of the cilia phenotype. We thus reveal primary cilia mechanisms impacting aRG dynamics in physiological and pathological conditions.

Adrenal Cortical Neoplasm with Uncertain Malignant Potential Arising in the Heterotopic Adrenal Cortex in the Liver of a Patient with Beckwith-Wiedemann Syndrome.

Patients with Beckwith-Wiedemann syndrome (BWS) are predisposed to developing embryonal tumors, with hepatoblastoma being the most common type. Our patient showed hemihypertrophy, macroglossia, and paternal uniparental disomy in chromosome 11 and was diagnosed with BWS. When the patient was 9 months old, a 2.5×1.5 cm oval hypoechoic exophytic mass was detected in the inferior tip of his right liver. Preoperative imaging identified it as hepatoblastoma; however, histologic, immunohistochemistry, and electron microscopic findings were compatible with adrenal cortical neoplasm with uncertain malignant potential. The origin of the adrenal tissue seemed to be heterotopic. Here, we describe for the first time an adrenal cortical neoplasm with uncertain malignant potential arising in the heterotopic adrenal cortex located in the liver of a patient with BWS.

Epileptogenic networks in nodular heterotopia: A stereoelectroencephalography study.

Defining the roles of heterotopic and normotopic cortex in the epileptogenic networks in patients with nodular heterotopia is challenging. To elucidate this issue, we compared heterotopic and normotopic cortex using quantitative signal analysis on stereoelectroencephalography (SEEG) recordings. Clinically relevant biomarkers of epileptogenicity during ictal (epileptogenicity index; EI) and interictal recordings (high-frequency oscillation and spike) were evaluated in 19 patients undergoing SEEG. These biomarkers were then compared between heterotopic cortex and neocortical regions. Seizures were classified as normotopic, heterotopic, or normoheterotopic according to respective values of quantitative analysis (EI ≥0.3). A total of 1,246 contacts were analyzed: 259 in heterotopic tissue (heterotopic cortex), 873 in neocortex in the same lobe of the lesion (local neocortex), and 114 in neocortex distant from the lesion (distant neocortex). No significant difference in EI values, high-frequency oscillations, and spike rate was found comparing local neocortex and heterotopic cortex at a patient level, but local neocortex appears more epileptogenic (p < 0.001) than heterotopic cortex analyzing EI values at a seizure level. According to EI values, seizures were mostly normotopic (48.5%) or normoheterotopic (45.5%); only 6% were purely heterotopic. A good long-term treatment response was obtained in only two patients after thermocoagulation and surgical disconnection. This is the first quantitative SEEG study providing insight into the mechanisms generating seizures in nodular heterotopia. We demonstrate that both the heterotopic lesion and particularly the normotopic cortex are involved in the epileptogenic network. This could open new perspectives on multitarget treatments, other than resective surgery, aimed at modifying the epileptic network.

Impairment of radial glial scaffold-dependent neuronal migration and formation of double cortex by genetic ablation of afadin

Studies of human brain malformations, such as lissencephaly and double cortex, have revealed the importance of neuronal migration during cortical development. Afadin, a membrane scaffolding protein, regulates the formation of adherens junctions (AJs) and cell migration to form and maintain tissue structures. Here, we report that mice with dorsal telencephalon-specific ablation of afadin gene exhibited defects similar to human double cortex, in which the heterotopic cortex was located underneath the normotopic cortex. The normotopic cortex of the mutant mice was arranged in the pattern similar to the cortex of the control mice, while the heterotopic cortex was disorganized. As seen in human patients, double cortex in the mutant mice was formed by impaired neuronal migration during cortical development. Genetic ablation of afadin in the embryonic cerebral cortex disrupted AJs of radial glial cells, likely resulting in the retraction of the apical endfeet from the ventricular surface and the dispersion of radial glial cells from the ventricular zone to the subventricular and intermediate zones. These results indicate that afadin is required for the maintenance of AJs of radial glial cells and that the disruption of AJs might cause an abnormal radial scaffold for neuronal migration. In contrast, the proliferation or differentiation of radial glial cells was not significantly affected. Taken together, these findings indicate that afadin is required for the maintenance of the radial glial scaffold for neuronal migration and that the genetic ablation of afadin leads to the formation of double cortex.

Congenital cerebellar dysplasia in White Leghorn chickens (Gallus gallus domesticus)

Congenital cerebellar anomalies have been rarely reported in birds. We examined cerebellums with disorganized folia from seven specific-pathogen-free White Leghorn chickens (Gallus gallus domesticus). Islands of heterotopic cortex were distributed from the deeper cortices to the medulla in the cerebellum. The characteristic lesions were composed of randomly admixed components of the cerebellar cortex, including Purkinje cells, a molecular layer and granular cells. Immunofluorescent analysis revealed Purkinje cells with haphazardly extended dendrites and a lack of Bergmann's glial fibres in the foci. Chicken parvovirus, Aino virus and avian retrovirus were not detected in the affected birds by polymerase chain reaction. This is the first report of cerebellar dysplasia in chickens possibly caused by a genetic abnormality.

A Radial Glia-Specific Role of RhoA in Double Cortex Formation

The positioning of neurons in the cerebral cortex is of crucial importance for its function as highlighted by the severe consequences of migrational disorders in patients. Here we show that genetic deletion of the small GTPase RhoA in the developing cerebral cortex results in two migrational disorders: subcortical band heterotopia (SBH), a heterotopic cortex underlying the normotopic cortex, and cobblestone lissencephaly, in which neurons protrude beyond layer I at the pial surface of the brain. Surprisingly, RhoA(-/-) neurons migrated normally when transplanted into wild-type cerebral cortex, whereas the converse was not the case. Alterations in the radial glia scaffold are demonstrated to cause these migrational defects through destabilization of both the actin and the microtubules cytoskeleton. These data not only demonstrate that RhoA is largely dispensable for migration in neurons but also showed that defects in radial glial cells, rather than neurons, can be sufficient to produce SBH.

Experimental Neuronal Migration Disorders Following the Administration of Ibotenate in Hamsters: The Role of the Subventricular Zone in the Development of Cortical Dysplasia

To examine the role of subventricular zone in cortical dysplasia, an experimental model was established using a neuronal tracing study. Ibotenate is a glutamate receptor agonist, and its intracerebral injection produces excitotoxic lesions mimicking microgyria and heterotopia. A total of 72 newborn hamsters were subjected. Biotinylated dextran amine was injected into the ganglionic eminence for the neuronal tracer. The cortical lesions and apoptotic cells were analyzed. In the microgyric cortex, terminal deoxynucleotidyl transferase-mediated 2' -deoxyuridine 5'-triphosphate-biotin end labeling-positive cells were increased and accumulated in the cortical folding. Biotinylated dextran amine-positive cells and fibers were derived from the dorsolateral subventricular zone and directed toward the cortical folding. In the heterotopic cortex, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate- biotin end labeling-positive cells were distributed around the heterotopia, but number of cells was not remarkable. Our findings suggest that the subventricular zone plays an important role in the formation of cortical dysplasia, especially in the microgyria, after excitatory neuronal injury.

Different structures involved during ictal and interictal epileptic activity in malformations of cortical development: an EEG-fMRI study

Malformations of cortical development (MCDs) are commonly complicated by intractable focal epilepsy. Epileptogenesis in these disorders is not well understood and may depend on the type of MCD. The cellular mechanisms involved in interictal and ictal events are notably different, and could be influenced independently by the type of pathology. We evaluated the relationship between interictal and ictal zones in eight patients with different types of MCD in order to better understand the generation of these activities: four had nodular heterotopia, two focal cortical dysplasia and two subcortical band heterotopia (double-cortex). We used the non-invasive EEG-fMRI technique to record simultaneously all cerebral structures with a high spatio-temporal resolution. We recorded interictal and ictal events during the same session. Ictal events were either electrical only or clinical with minimal motion. BOLD changes were found in the focal cortical dysplasia during interictal and ictal epileptiform events in the two patients with this disorder. Heterotopic and normal cortices were involved in BOLD changes during interictal and ictal events in the two patients with double cortex, but the maximum BOLD response was in the heterotopic band in both patients. Only two of the four patients with nodular heterotopia showed involvement of a nodule during interictal activity. During seizures, although BOLD changes affected the lesion in two patients, the maximum was always in the overlying cortex and never in the heterotopia. For two patients intracranial recordings were available and confirm our findings. The dysplastic cortex and the heterotopic cortex of band heterotopia were involved in interictal and seizure processes. Even if the nodular gray matter heterotopia may have the cellular substrate to produce interictal events, the often abnormal overlying cortex is more likely to be involved during the seizures. The non-invasive BOLD study of interictal and ictal events in MCD patients may help to understand the role of the lesion in epileptogenesis and also determine the potential surgical target.

Characterization of the HeCo Mutant Mouse: A New Model of Subcortical Band Heterotopia Associated with Seizures and Behavioral Deficits

In human, neuronal migration disorders are commonly associated with developmental delay, mental retardation, and epilepsy. We describe here a new mouse mutant that develops a heterotopic cortex (HeCo) lying in the dorsolateral hemispheric region, between the homotopic cortex (HoCo) and subcortical white matter. Cross-breeding demonstrated an autosomal recessive transmission. Birthdating studies and immunochemistry for layer-specific markers revealed that HeCo formation was due to a transit problem in the intermediate zone affecting both radially and tangentially migrating neurons. The scaffold of radial glial fibers, as well as the expression of doublecortin is not altered in the mutant. Neurons within the HeCo are generated at a late embryonic age (E18) and the superficial layers of the HoCo have a correspondingly lower cell density and layer thickness. Parvalbumin immunohistochemistry showed the presence of gamma-aminobutyric acidergic cells in the HeCo and the mutant mice have a lowered threshold for the induction of epileptic seizures. The mutant showed a developmental delay but, in contrast, memory function was relatively spared. Therefore, this unique mouse model resembles subcortical band heterotopia observed in human. This model represents a new and rare tool to better understand cortical development and to investigate future therapeutic strategies for refractory epilepsy.

VASCULAR MALFORMATION AND CHOROID PLEXUS ADRENAL HETEROTOPIA: NEW FINDINGS IN BECKWITH-WIEDEMANN SYNDROME?

Large congenital arteriovenous malformations (AVM) may result in heart failure and death. We are reporting such combination with the AVM localized to the right thoracobrachial region. Remarkable postmortem findings included right renal and adrenal hemihyperplasia; the right adrenal fetal cortex presenting cytomegaly, endocrine pancreas hyperplasia, and heterotopic adrenal cortex with cytomegaly in the left lateral ventricle choroids plexus. The combination appears to be unique. The only previously reported example of adrenal cortex in the choroid plexus presented several features strongly suggestive of Beckwith-Wiedemann syndrome. Therefore, we postulate that additional uncommon findings in Beckwith-Wiedemann syndrome may include arteriovenous malformations and heterotopic adrenal tissue in choroids plexus.

Laparoscopic upper pole partial nephrectomy with concomitant en bloc adrenalectomy

Objectives To report our experience with laparoscopic partial nephrectomy for renal tumor with concomitant adrenalectomy. An upper pole renal tumor may contiguously involve the adrenal gland, requiring concomitant adrenalectomy. Although commonly performed in the setting of laparoscopic radical nephrectomy, concomitant adrenalectomy has not been described during laparoscopic partial nephrectomy. Methods Four patients with an upper pole renal tumor and suspected adrenal involvement underwent laparoscopic partial nephrectomy with concomitant ipsilateral adrenalectomy. Preoperative three-dimensional computed tomography revealed the renal tumor to be closely abutting the adrenal gland in 3 patients and a 4-cm adrenal mass in 1 patient. The mean renal tumor size was 3.2 cm (range 1.4 to 6.6). To maintain oncologic principles, our transperitoneal laparoscopic technique excises the adrenal gland en bloc with the renal tumor. As such, adrenalectomy is performed first, followed by partial nephrectomy, incorporating hilar control, tumor excision, and sutured renal reconstruction. Results All four procedures were performed without open conversion or intraoperative complications. The mean renal warm ischemia time was 36 minutes, estimated blood loss 169 mL, total operating time 3.9 hours, and hospital stay 3.2 days. One patient developed a transient urinary leak postoperatively. Pathologic examination of the renal tumor revealed renal cell carcinoma (n = 1), dystrophic calcification with ectopic bone formation (n = 1), adult mesoblastic nephroma (n = 1), and subcapsular heterotopic adrenal cortex with cyst (n = 1), all with negative surgical margins. Pathologic examination of the adrenal gland revealed adenoma in 1 case and a normal adrenal gland without malignant involvement in 3 cases. All patients were disease free at last follow-up (mean 6.2 months, range 2 to 12). Conclusions In patients with an upper pole renal tumor and radiologically suspected adrenal involvement, laparoscopic partial nephrectomy with concomitant adrenalectomy can be performed efficaciously respecting oncologic principles.

Magnetoencephalographic studies of two cases of diffuse subcortical laminar heterotopia or so-called double cortex

Two cases (a young male and a girl, suffering intractable epilepsy) of diffuse subcortical laminar heterotopia, or so-called double cortex (DC) have been investigated using magnetoencephalography (MEG). MEG confirmed involvement of both cortices (hetero- and normocortex) in the genesis of interictal spikes, and, according to the heterogeneity of DC syndrome, some differences were observed: spike initiation in the normocortex and latter involvement of the heterotopic cortex in the man, and rather a cancellation in both cortices in the girl. In addition, participation of heterotopic cortex in physiological activities could be demonstrated in the man.

Reduction of spontaneous inhibitory synaptic activity in experimental heterotopic gray matter.

Neuronal heterotopia has a strong association with epilepsy, but the mechanisms that underlie this relationship are largely unknown. We have utilized the in utero irradiated rat model to study circuit abnormalities in experimentally induced subcortical heterotopic gray matter. Spontaneous and miniature inhibitory (IPSCs) and excitatory (EPSCs) postsynaptic currents were recorded from visualized heterotopic pyramidal neurons in in vitro hemispheric slices and compared with control neocortical pyramidal neurons using the whole cell patch-clamp technique. The frequency of spontaneous and miniature IPSCs was significantly reduced in pyramidal neurons from heterotopic cortex. Amplitude and kinetics of IPSCs were not different between the two groups. Spontaneous and miniature EPSCs were not different between the two groups. Short-term synaptic plasticity of stimulus-evoked EPSCs showed depression in heterotopic neurons and facilitation in control pyramidal neurons. This study shows a selective impairment of the GABAergic circuitry in experimental heterotopic gray matter. We have reported similar findings in normotopic dysplastic cortex from this model. Taken together, these studies demonstrate a pervasive defect in inhibition throughout the cortex of irradiated rats with cortical dysplasia and neuronal heterotopia. This may have important implications regarding cortical development and function following in utero injuries.

HETEROTOPIC ADRENAL CORTICAL ADENOMA MASQUERADING AS METASTATIC RENAL CELL CARCINOMA

It is known that a heterotopic adrenal gland may be located in the upper abdomen or anywhere along the path of descent of the gonads.'.* Such adrenal glands may undergo hyperplasia in response to increased levels of adrenocorticotropic hormone, and they may serve as a site of origin of a cortical neoplasm.3 Conceivably heterotopic adrenal cortical hyperplasia and/or adenoma may be confused with certain primary or metastatic tumors. We report a case of adrenal cortical adenoma arising from the heterotopic adrenal cortex in the gastroesophageal junction that was misdiagnosed as metastatic renal cell carcinoma before and during radical nephrectomy for primary renal cell carcinoma. To our knowledge our case represents the first report of heterotopic adrenal cortical adenoma at the gastroesophageal junction mimicking metastatic renal cell carcinoma. CASE REPORT A 60-year-old black man presented with hematuria. Subsequently excretory urography and computerized tomography (CT) revealed a 12 x 12 cm. mass in the upper pole of the right kidney consistent with renal cell carcinoma (fig. 1). In addition, CT and esophagogastroduodenoscopic ultrasound showed a solid 2 x 3 cm. lesion at the gastroesophageal junction immediately outside the gastroesophageal wall. Transgastric fine needle aspiration of the mass demonstrated clusters of epithelial cells with clear cytoplasm consistent with metastatic renal cell carcinoma. Biopsy of the gastric mucosa revealed chronic active gastritis with no evidence of tumor in the gastric wall. Therapeutic approaches were significantly complicated by these apparent gastroesophageal metastases. After considering the risks, benefits and alternatives the patient elected right radical nephrectomy followed by exploration of the lesion at the gastroesophageal junction. During surgery the 2.5 to 3.0 cm., soft, rubbery, bright yellow-orange mass was not

Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of thetish mutant rat

Orthograde and retrograde tracers were used to examine subcortical connections of neurons in the neurological mutant tish rat. This animal exhibits bilateral heterotopia similar to those observed in epileptic humans with subcortical band heterotopia. Terminal varicosities were labeled in the striatum, thalamus, brainstem, and spinal cord following injections of the anterograde tracer biotinylated dextran amine (BDA) into the heterotopic cortex. The general topography of corticothalamic projections was evaluated by injecting the retrograde tracer Fluoro-Gold (FG) into ventral thalamic nuclei. Retrograde labeling of small-to-medium sized neurons was observed in layer VI of topographically restricted portions of the normotopic cortex. Similar appearing cells were labeled in the neighboring portions of the underlying heterotopia; however, these neurons did not display characteristic lamination or radial orientation. Thalamocortical terminals labeled by injecting BDA into the ventroposterolateral nucleus (VPL) were observed primarily in layer IV of the medial aspect of the normotopic somatosensory cortex. In contrast, a radial column of terminals was present in the underlying heterotopia. Typical barrel labeling was found in the lateral aspect of the normotopic somatosensory cortex after injecting the ventroposteromedial nucleus (VPM), whereas more diffuse patches of labeling were observed in the underlying heterotopia. Heterotopic neurons in the tish cortex, thus, exhibit characteristic features of subcortical connectivity. Both normotopic and heterotopic neurons in the tish brain project to appropriate subcortical sites and establish bidirectional topographic connections with the thalamus. These results suggest that primary sensory-motor information is represented in a parallel manner in the normotopic and heterotopic cortices of the tish rat.

Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of the tish mutant rat

Orthograde and retrograde tracers were used to examine subcortical connections of neurons in the neurological mutant tish rat. This animal exhibits bilateral heterotopia similar to those observed in epileptic humans with subcortical band heterotopia. Terminal varicosities were labeled in the striatum, thalamus, brainstem, and spinal cord following injections of the anterograde tracer biotinylated dextran amine (BDA) into the heterotopic cortex. The general topography of corticothalamic projections was evaluated by injecting the retrograde tracer Fluoro-Gold (FG) into ventral thalamic nuclei. Retrograde labeling of small-to-medium sized neurons was observed in layer VI of topographically restricted portions of the normotopic cortex. Similar appearing cells were labeled in the neighboring portions of the underlying heterotopia; however, these neurons did not display characteristic lamination or radial orientation. Thalamocortical terminals labeled by injecting BDA into the ventroposterolateral nucleus (VPL) were observed primarily in layer IV of the medial aspect of the normotopic somatosensory cortex. In contrast, a radial column of terminals was present in the underlying heterotopia. Typical barrel labeling was found in the lateral aspect of the normotopic somatosensory cortex after injecting the ventroposteromedial nucleus (VPM), whereas more diffuse patches of labeling were observed in the underlying heterotopia. Heterotopic neurons in the tish cortex, thus, exhibit characteristic features of subcortical connectivity. Both normotopic and heterotopic neurons in the tish brain project to appropriate subcortical sites and establish bidirectional topographic connections with the thalamus. These results suggest that primary sensory-motor information is represented in a parallel manner in the normotopic and heterotopic cortices of the tish rat. J. Comp. Neurol. 395:29–42, 1998. © 1998 Wiley-Liss, Inc.

Vision despite tomographic absence of the occipital cortex

A 14-month-old boy with developmental delay showed microcephaly, spastic diplegia, central visual fixation and an esotropia. A head tomographic scan disclosed absence of normal occipital cortex and electroencephalography showed markedly reduced voltages over the occipital region. Visual development in this patient may be related to heterotopic occipital cortex of a functioning non-striate system of visual processing. Visual function cannot be predicted when severe developmental anomalies of the occipital cortex are detected with computerized tomography.

Neuroimaging studies of connectivity in epileptic neural networks

Event Abstract Back to Event Neuroimaging studies of connectivity in epileptic neural networks N. J. Thai1*, D. Brazzo1, P. L. Furlong1, 2 and S. Seri1, 2 1 MRI Research Unit, Aston Brain Centre, United Kingdom 2 Aston University , Wellcome trust laboratory for MEG studies, United Kingdom Aim: The recent theoretical shift towards understanding the brain in terms of neural network/systems in neuroimaging studies has provided a means towards understanding how these neural networks interact and underpin function in both the healthy and pathological brain. Here we report two case studies that demonstrate how the application of functional and effective connectivity analysis can enhance our understanding of epileptic neural networks. Methods: In the first case study we report on a presurgical patient with unilateral right hemisphere Periventricular Nodular Heterotopia (PNH) using fMRI for localisation of externally cued and internally generated finger movements, and compared the patient results with her twin sister. Functional interactions were computed with PPIs in SPM8. MEG data was collected for the patient for a total recording time of 1 hour to capture interictal MEG sharp waves, spikes and bursts of rhythmic activity. SAMg2 analysis was performed to identify the brain regions reaching statistical significance for the presence of increased kurtosis. In the second case study, simultaneous EEG and fMRI was recorded on a patient with Landau Kleffner Syndrome (LKS) to identify whether the brain regions showing interictal EEG epileptic spikes presented haemodynamic signal changes that correspond to the time course of the 3D source distribution of cortical activation during the focal EEG discharges. Effective connectivity was computed on the fMRI data with dynamic causal modeling in SPM8. Results: In the PNH patient, there were significant functional interactions between the heterotopic cortex, motor cortex and a right frontal region that was highly concordant with the MEG epileptogenic source localisation. In the LKS patient, results show high concordance between hemodynamic changes and EEG source localization. The connectivity analysis suggests a primary involvement of the superior temporal gyrus (STG) spreading to lateral frontal cortex associated with interictal spikes. Conclusion: In the first case study connectivity analysis identified an epileptic network which includes heterotopic and the irritative zone in the frontal areas. In the second case study, connectivity patterns suggest that the functional underpinnings of LKS syndrome is related to a widespread dysfunction which extends beyond the STG. Neuroimaging connectivity studies can provide valuable clinical insights into the epileptic neural networks underlying the syndrome. Acknowledgments: Dr. N. J. Thai was partly supported by The Birmingham Children's Hospital, MRI scan costs were supported by the Lord Dowding Fund for Humane Research and MEG scan costs were supported by the Dr. Hadwen Trust for Humane Research. Conference: NeuroMath COST Action BM0601: Neurodynamic Insight into Functional Connectivity, Cognition, and Consciousness, Dubrovnik, Croatia, 27 Mar - 28 Mar, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Thai NJ, Brazzo D, Furlong PL and Seri S (2010). Neuroimaging studies of connectivity in epileptic neural networks. Front. Neurosci. Conference Abstract: NeuroMath COST Action BM0601: Neurodynamic Insight into Functional Connectivity, Cognition, and Consciousness. doi: 10.3389/conf.fnins.2010.05.00031 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Jul 2010; Published Online: 24 Jul 2010. * Correspondence: N. J Thai, MRI Research Unit, Aston Brain Centre, Birmingham, United Kingdom, j.n.thai@aston.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers N. J Thai D. Brazzo P. L Furlong S. Seri Google N. J Thai D. Brazzo P. L Furlong S. Seri Google Scholar N. J Thai D. Brazzo P. L Furlong S. Seri PubMed N. J Thai D. Brazzo P. L Furlong S. Seri Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.