An official website of the United States government
Abstract ObjectiveThis study was undertaken to evaluate the influence that subject‐specific factors have on intracranial interictal epileptiform discharge (IED) rates in persons with refractory epilepsy. MethodsOne hundred fifty subjects with intracranial electrodes performed multiple sessions of a free recall memory task; this standardized task controlled for subject attention levels. We utilized a dominance analysis to rank the importance of subject‐specific factors based on their relative influence on IED rates. Linear mixed‐effects models were employed to comprehensively examine factors with highly ranked importance. ResultsAntiseizure medication (ASM) status, time of testing, and seizure onset zone (SOZ) location were the highest‐ranking factors in terms of their impact on IED rates. The average IED rate of electrodes in SOZs was 34% higher than the average IED rate of electrodes outside of SOZs (non‐SOZ;p < .001). However, non‐SOZ electrodes had similar IED rates regardless of the subject's SOZ location (p = .99). Subjects on older generation (p < .001) and combined generation (p < .001) ASM regimens had significantly lower IED rates relative to the group taking no ASMs; newer generation ASM regimens demonstrated a nonsignificant association with IED rates (p = .13). Of the ASMs included in this study, the following ASMs were associated with significant reductions in IED rates: levetiracetam (p < .001), carbamazepine (p < .001), lacosamide (p = .03), zonisamide (p = .01), lamotrigine (p = .03), phenytoin (p = .03), and topiramate (p = .01). We observed a nonsignificant association between time of testing and IED rates (morning–afternoonp = .15, morning–eveningp = .85, afternoon–eveningp = .26). SignificanceThe current study ranks the relative influence that subject‐specific factors have on IED rates and highlights the importance of considering certain factors, such as SOZ location and ASM status, when analyzing IEDs for clinical or research purposes.
more »
« less
Interictal epileptiform discharges contribute to word‐finding difficulty in epilepsy through multiple cognitive mechanisms
Abstract ObjectiveCognitive impairment often impacts quality of life in epilepsy even if seizures are controlled. Word‐finding difficulty is particularly prevalent and often attributed to etiological (static, baseline) circuit alterations. We sought to determine whether interictal discharges convey significant superimposed contributions to word‐finding difficulty in patients, and if so, through which cognitive mechanism(s). MethodsTwenty‐three patients undergoing intracranial monitoring for drug‐resistant epilepsy participated in multiple tasks involving word production (auditory naming, short‐term verbal free recall, repetition) to probe word‐finding difficulty across different cognitive domains. We compared behavioral performance between trials with versus without interictal discharges across six major brain areas and adjusted for intersubject differences using mixed‐effects models. We also evaluated for subjective word‐finding difficulties through retrospective chart review. ResultsSubjective word‐finding difficulty was reported by the majority (79%) of studied patients preoperatively. During intracranial recordings, interictal epileptiform discharges (IEDs) in the medial temporal lobe were associated with long‐term lexicosemantic memory impairments as indexed by auditory naming (p = .009), in addition to their established impact on short‐term verbal memory as indexed by free recall (p = .004). Interictal discharges involving the lateral temporal cortex and lateral frontal cortex were associated with delayed reaction time in the auditory naming task (p = .016 andp = .018), as well as phonological working memory impairments as indexed by repetition reaction time (p = .002). Effects of IEDs across anatomical regions were strongly dependent on their precise timing within the task. SignificanceIEDs appear to act through multiple cognitive mechanisms to form a convergent basis for the debilitating clinical word‐finding difficulty reported by patients with epilepsy. This was particularly notable for medial temporal spikes, which are quite common in adult focal epilepsy. In parallel with the treatment of seizures, the modulation of interictal discharges through emerging pharmacological means and neurostimulation approaches may be an opportunity to help address devastating memory and language impairments in epilepsy.
more »
« less
- Award ID(s):
- 2148753
- PAR ID:
- 10468885
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Epilepsia
- Volume:
- 64
- Issue:
- 12
- ISSN:
- 0013-9580
- Format(s):
- Medium: X Size: p. 3266-3278
- Size(s):
- p. 3266-3278
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Implantable sensors for recording neural activity are often used for a variety of applications, including epilepsy studies. Current versions of these recorders are highly-invasive impractical implants and undesirable in daily life. To address this, for the first time we present a novel fully- implantable and passive system for recording characteristic epileptic activity. In this paper, we focus on recording interictal epileptiform discharges (IEDs), known indicators of clinical significance. IEDs can serve to identify the location of seizure onset zones. Notably, in the case of temporal lobe epilepsy (TLE). Here, we present IED signals recorded using neural probes previously tested with our system and demonstrated to be capable of sensing signals as low as 15 μVpp in amplitude. These recordings refer to actual animal experiments and are indicative of the broad spectrum of neural signals that can be recorded.more » « less
-
Abstract This study examined putative benefits of testing and production for learning new languages. Undergraduates (N= 156) were exposed to Turkish spoken dialogues under varying learning conditions (retrieval practice, comprehension, verbal repetition) in a computer‐assisted language learning session. Participants completed pre‐ and posttests of number‐ and case‐marking comprehension, a vocabulary test, and an explicit awareness questionnaire. Controlling for nonverbal ability and pretest scores, the retrieval‐practice group performed highest overall. For number/case marking, the comprehension and retrieval‐practice groups outperformed the verbal‐repetition group, suggesting benefits of either recognition‐ or recall‐based testing. For vocabulary, the verbal‐repetition and retrieval‐practice groups outperformed the comprehension group, indicating benefits of overt production. Case marking was easier to learn than number marking, suggesting advantages for learning word‐final inflections. Explicit awareness correlated with comprehension accuracy, yet some participants demonstrated above‐chance comprehension without showing awareness. Findings indicate the value of incorporating both practice tests and overt production in language pedagogy.more » « less
-
null (Ed.)Using electroencephalography (EEG) data from epileptic patients 1 , we investigated and compared functional connectivity networks of three various types of epileptiform discharges (ED; single, complex & repetitive spikes) in 4 regions of the brain. Our results showed different connectivity patterns among three ED types within-and between-brain regions. The one-way ANOVA test indicated significant differences between the mean of the average connectivity matrices (ACMs) of the single spike, which characterize focal epilepsy, and the other two ED types (complex & repetitive) which characterize generalized epilepsy. The interictal EEG segments, through the connectivity patterns they yield, could be considered as one of the key indicators for the diagnosis of focal or generalized epilepsy.more » « less
-
Influence of age at seizure onset on the acquisition of neurodevelopmental skills in an SCN8A cohortAbstract ObjectiveTo characterize a cohort of patients withSCN8A‐related epilepsy and to perform analyses to identify correlations involving the acquisition of neurodevelopmental skills. MethodsWe analyzed patient data (n = 91) submitted to an online registry tailored to characteristics of children withSCN8Avariants. Participants provided information on the history of their child's seizures, medications, comorbidities, and developmental skills based on the DenverIIitems. Spearman rank tests were utilized to test for correlations among a variety of aspects of seizures, medications, and neurodevelopmental progression. ResultsThe 91 participants carried 71 missense variants (41 newly reported) and three truncating variants. Ages at seizure onset ranged from birth to >12 months of age (mean ± SD = 5 months 21 days ± 7 months 14 days). Multiple seizure types with multimodal onset times and developmental delay were observed as general features of this cohort. We found a positive correlation between a developmental score based upon percentage of acquired skills and the age at seizure onset, current seizure freedom, and initial febrile seizures. Analyses of cohort subgroups revealed clear distinctions between patients who had a single reported variant inSCN8Aand those with an additional variant reported in a gene other thanSCN8A, as well as between patients with different patterns of regression before and at seizure onset. SignificanceThis is the first study of anSCN8A patient cohort of this size and for which correlations between age at seizure onset and neurodevelopment were investigated. Our correlation studies suggest that variants of uncertain significance should be considered in assessing children withSCN8A‐related disorders. This study substantially improves the characterization of this patient population and our understanding of the neurodevelopmental effects associated with seizures forSCN8A patients, and provides a clinical context at initial presentation that may be prognostic for developmental outcome.more » « less
