Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficits
There is a well-described association between childhood epilepsy and pervasive cognitive and behavioral deficits. Often these children not only have ictal EEG events, but also frequent interictal abnormalities. The precise role of these interictal discharges in cognition remains unclear. In order to...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-03-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996113003240 |
| _version_ | 1818724444682584064 |
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| author | Amanda E. Hernan Abigail Alexander Kyle R. Jenks Jeremy Barry Pierre-Pascal Lenck-Santini Elena Isaeva Gregory L. Holmes Rod C. Scott |
| author_facet | Amanda E. Hernan Abigail Alexander Kyle R. Jenks Jeremy Barry Pierre-Pascal Lenck-Santini Elena Isaeva Gregory L. Holmes Rod C. Scott |
| author_sort | Amanda E. Hernan |
| collection | DOAJ |
| description | There is a well-described association between childhood epilepsy and pervasive cognitive and behavioral deficits. Often these children not only have ictal EEG events, but also frequent interictal abnormalities. The precise role of these interictal discharges in cognition remains unclear. In order to understand the relationship between frequent epileptiform discharges during neurodevelopment and cognition later in life, we developed a model of frequent focal interictal spikes (IIS). Postnatal day (p) 21 rats received injections of bicuculline methiodine into the prefrontal cortex (PFC). Injections were repeated in order to achieve 5 consecutive days of transient inhibitory/excitatory imbalance resulting in IIS. Short-term plasticity (STP) and behavioral outcomes were studied in adulthood. IIS is associated with a significant increase in STP bilaterally in the PFC. IIS rats did not show working memory deficits, but rather showed marked inattentiveness without significant alterations in motivation, anxiety or hyperactivity. Rats also demonstrated significant deficits in social behavior. We conclude that GABAergic blockade during early-life and resultant focal IIS in the PFC disrupt neural networks and are associated with long-term consequences for behavior at a time when IIS are no longer present, and thus may have important implications for ADHD and autism spectrum disorder associated with childhood epilepsy. |
| first_indexed | 2024-12-17T21:26:31Z |
| format | Article |
| id | doaj.art-ce7b2806d1fd475ea262edd552d279a0 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T21:26:31Z |
| publishDate | 2014-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-ce7b2806d1fd475ea262edd552d279a02022-12-21T21:32:02ZengElsevierNeurobiology of Disease1095-953X2014-03-01632534Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficitsAmanda E. Hernan0Abigail Alexander1Kyle R. Jenks2Jeremy Barry3Pierre-Pascal Lenck-Santini4Elena Isaeva5Gregory L. Holmes6Rod C. Scott7Department of Neurology, Program in Experimental and Molecular Medicine Dartmouth, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA 05405; Correspondence to: A. Hernan, 95 Carrigan Drive, Stafford 118F, Burlington, VT 05405, USA.Department of Neurology, Program in Experimental and Molecular Medicine Dartmouth, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USADepartment of Neurology, Program in Experimental and Molecular Medicine Dartmouth, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USADepartment of Neurology, Program in Experimental and Molecular Medicine Dartmouth, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA 05405Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA 05405State Key Laboratory for Molecular and Cellular Biology, Kiev 01601, Ukraine; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA 05405Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA 05405Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA 05405; University College London, Institute of Child Health, London WC1N 1EH, UK; Correspondence to: R. Scott, 95 Carrigan Drive, Stafford 118D, Burlington, VT 05405, USA.There is a well-described association between childhood epilepsy and pervasive cognitive and behavioral deficits. Often these children not only have ictal EEG events, but also frequent interictal abnormalities. The precise role of these interictal discharges in cognition remains unclear. In order to understand the relationship between frequent epileptiform discharges during neurodevelopment and cognition later in life, we developed a model of frequent focal interictal spikes (IIS). Postnatal day (p) 21 rats received injections of bicuculline methiodine into the prefrontal cortex (PFC). Injections were repeated in order to achieve 5 consecutive days of transient inhibitory/excitatory imbalance resulting in IIS. Short-term plasticity (STP) and behavioral outcomes were studied in adulthood. IIS is associated with a significant increase in STP bilaterally in the PFC. IIS rats did not show working memory deficits, but rather showed marked inattentiveness without significant alterations in motivation, anxiety or hyperactivity. Rats also demonstrated significant deficits in social behavior. We conclude that GABAergic blockade during early-life and resultant focal IIS in the PFC disrupt neural networks and are associated with long-term consequences for behavior at a time when IIS are no longer present, and thus may have important implications for ADHD and autism spectrum disorder associated with childhood epilepsy.http://www.sciencedirect.com/science/article/pii/S0969996113003240Pediatric epilepsyInterictal spikesAttentionSocial behaviorShort-term plasticityPrefrontal cortex |
| spellingShingle | Amanda E. Hernan Abigail Alexander Kyle R. Jenks Jeremy Barry Pierre-Pascal Lenck-Santini Elena Isaeva Gregory L. Holmes Rod C. Scott Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficits Neurobiology of Disease Pediatric epilepsy Interictal spikes Attention Social behavior Short-term plasticity Prefrontal cortex |
| title | Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficits |
| title_full | Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficits |
| title_fullStr | Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficits |
| title_full_unstemmed | Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficits |
| title_short | Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficits |
| title_sort | focal epileptiform activity in the prefrontal cortex is associated with long term attention and sociability deficits |
| topic | Pediatric epilepsy Interictal spikes Attention Social behavior Short-term plasticity Prefrontal cortex |
| url | http://www.sciencedirect.com/science/article/pii/S0969996113003240 |
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