Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficits
Open accessAbstract
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.
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Childhood frontal lobe epilepsy (FLE) has various clinical outcomes but most often results in multi-cognitive symptoms.
“Epilepsy, specifically childhood frontal lobe epilepsy (FLE) has various clinical outcomes but most often resulting in multi-cognitive symptoms [384–387].”
From Development of prefrontal cortex (2022) · cites this paper as [387]
The Introduction (page not provided) describes varied cognitive and behavioral impairments in children with epilepsy, and the paper's prefrontal rat model shows later attention and social deficits. It does not establish that childhood frontal lobe epilepsy specifically most often causes multiple cognitive symptoms; the Introduction instead says almost 40% of children with epilepsy have comorbid behavioral deficits. (LLM, conf=0.88)
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- Authors
- Hernan, A. E., Alexander, A., Jenks, K. R., Barry, J., Lenck-Santini, P.-P., Isaeva, E., Holmes, G. L., & Scott, R. C.
- Affiliations
- Dartmouth College (US)
- University of Vermont (US)
- Corresponding author
- Hernan, Amanda E.
- Scott, Rod C.
- ORCID
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 63
- Pages
- 25-34
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC4397918
- OpenAlex
- W2045096194
- Cited by
- 73
- References
- 46
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 7 · 2021: 2 · 2020: 5 · 2019: 8 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 11 · 2014: 4
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Emmory R. Shapses Research Fund
- Great Ormond Street Children's Charity
- State Foundation of Fundamental Research of Ukraine (F46.2/001)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- interictal epileptiform discharges, prefrontal cortex, short-term plasticity, pediatric epilepsy, inattention, social behavior deficits, working memory, attention deficit hyperactivity disorder, autism spectrum disorder, rat model
- MeSH terms
- Animals, Animals, Newborn, Attention Deficit Disorder with Hyperactivity, Disease Models, Animal, Electroencephalography, Epilepsy, Exploratory Behavior, Male, Memory, Short-Term, Motivation, Neuronal Plasticity, Social Behavior Disorders, Time Factors, Rats, Sprague-Dawley, Prefrontal Cortex, Rats, In Vitro Techniques
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