Objective
Reorganization of the language network from typically left‐lateralized frontotemporal regions to bilaterally distributed or right‐lateralized networks occurs in anywhere from 25%–30% of ...patients with focal epilepsy. In patients who have been recently diagnosed with epilepsy, an important question remains as to whether it is the presence of seizures or the underlying epilepsy etiology that leads to atypical language representations. This question becomes even more interesting in pediatric samples, where the typical developmental processes of the language network may confer more variability and plasticity in the language network. We assessed a carefully selected cohort of children with recent‐onset epilepsy to examine whether it is the effects of seizures or their underlying cause that leads to atypical language lateralization.
Methods
We used functional magnetic resonance imaging (fMRI) to compare language laterality in children with recently diagnosed focal unaware epilepsy and age‐matched controls. Age at epilepsy onset (age 4 to 6 years vs age 7 to 12 years) was also examined to determine if age at onset influenced laterality.
Results
The majority of recent‐onset patients and controls exhibited left‐lateralized language. There was a significant interaction such that the relationship between epilepsy duration and laterality differed by age at onset. In children with onset after age 6, a longer duration of epilepsy was associated with less left‐lateralized language dominance. In contrast, in children with onset between 4 and 6 years of age, a longer duration of epilepsy was not associated with less left language dominance.
Significance
Our results demonstrate that although language remained largely left‐lateralized in children recently diagnosed with epilepsy, the impact of seizure duration depended on age at onset, indicating that the timing of developmental and disease factors are important in determining language dominance.
Focal cortical dysplasia (FCD) is the most common etiology of surgically-remediable epilepsy in children. Eighty-seven percent of patients with FCD develop epilepsy (75% is pharmacoresistant epilepsy ...PRE). Focal to bilateral tonic-clonic (FTBTC) seizures are associated with worse surgical outcomes. We hypothesized that children with FCD-related epilepsy with FTBTC seizures are more likely to develop PRE due to lesion interaction with restricted cortical neural networks.
Patients were selected retrospectively from radiology and surgical databases from Children's National Hospital.
3T magnetic resonance imaging (MRI)-confirmed FCD from January 2011 to January 2020; ages 0 days to 22 years at MRI; and 18 months of documented follow-up. FCD dominant network (Yeo 7-network parcellation) was determined. Association of FTBTC seizures with epilepsy severity, surgical outcome, and dominant network was tested. Binomial regression was used to evaluate predictors (FTBTC seizures, age at seizure onset, pathology, hemisphere, lobe) of pharmacoresistance and Engel outcome. Regression was used to evaluate predictors (age at seizure onset, pathology, lobe, percentage default mode network DMN overlap) of FTBTC seizures.
One hundred seventeen patients had a median age at seizure onset of 3.00 years (interquartile range IQR .42-5.59 years). Eighty-three patients had PRE (71%); 34 had pharmacosensitive epilepsy (PSE) (29%). Twenty patients (17%) had FTBTC seizures. Seventy-three patients underwent epilepsy surgery. Multivariate regression showed that FTBTC seizures are associated with an increased risk of PRE (odds ratio OR 6.41, 95% confidence interval CI 1.21-33.98, p = .02). FCD hemisphere/lobe was not associated with PRE. Percentage DMN overlap predicts FTBTC seizures. Seventy-two percent (n = 52) overall and 53% (n = 9) of patients with FTBTC seizures achieved Engel class I outcome.
In a heterogeneous population of surgical and non-operated patients with FCD-related epilepsy, the presence of FTBTC seizures is associated with a tremendous risk of PRE. This finding is a recognizable marker to help neurologists identify those children with FCD-related epilepsy at high risk of PRE and can flag patients for earlier consideration of potentially curative surgery. The FCD-dominant network also contributes to FTBTC seizure clinical expression.
A survey of 146 pediatric care providers (PCPs) revealed that 75.3% were unaware that children with epilepsy were at risk of death, specifically from sudden unexpected (or unexplained) death in ...epilepsy (SUDEP). PCPs assume that the treating neurologist discusses these risks. Increasing PCPs' knowledge of SUDEP will help address the care gap related to informing families about SUDEP.
Epilepsy affects 2.2 million adults in the USA, with 1 in 26 people developing epilepsy at some point in their lives. Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy as medial ...structures, and the hippocampus in particular, are prone to generating seizures. Selective anterior temporal resection (which removes the hippocampus) is the most effective intractable TLE treatment, but given the critical role of the mesial temporal lobe in memory functioning, resection can have negative effects on this crucial cognitive skill. To minimize the adverse impact of temporal lobe surgery on memory functioning, reliable pre-surgical guides are needed. Clinical functional magnetic resonance imaging (fMRI) provides reliable, noninvasive guidance of language functioning and plays a growing role in the pre-surgical evaluation for epilepsy patients; however, localization of memory function in children with epilepsy using fMRI has not been established. Aside from the lack of neuroimaging memory studies in children with TLE, studies of typical development are limited. This review will focus on the functional anatomy of memory systems throughout development, with a focus on TLE. TLE provides the ideal model from which to understand memory function and the limits of plasticity and compensation/reorganization throughout development.
Listening and reading comprehension of paragraph-length material are considered higher-order language skills fundamental to social and academic functioning. Using ecologically relevant language ...stimuli that were matched for difficulty according to developmental level, we analyze the effects of task, age, neuropsychological skills, and post-task performance on fMRI activation and hemispheric laterality. Areas of supramodal language processing are identified, with the most robust region being left-lateralized activation along the superior temporal sulcus. Functionally, this conjunction has a role in semantic and syntactic processing, leading us to refer to this conjunction as “comprehension cortex.” Different from adults, supramodal areas for children include less extensive inferior frontal gyrus but more extensive right cerebellum and right temporal pole. Broader neuroanatomical pathways are recruited for reading, reflecting the more active processing and larger set of cognitive demands needed for reading compared to listening to stories. ROI analyses reveal that reading is a less lateralized language task than listening in inferior frontal and superior temporal areas, which likely reflects the difficulty of the task as children in this study are still developing their reading skills. For listening to stories, temporal activation is stable by age four with no correlations with age, neuropsychological skills or post-task performance. In contrast, frontal activation during listening to stories occurs more often in older children, and frontal activation is positively correlated with better performance on comprehension questions, suggesting that the activation of frontal networks may reflect greater integration and depth of story processing.
Functional MRI provides a powerful means to identify and trace the evolution, development, and consolidation of cognitive neural networks through normal childhood. Neural network perturbations due to ...disease and other adverse factors during development can also be explored. Studies performed to date suggest that normal children older than 5 years show activation maps comparable to adults for similar cognitive paradigms. Minor differences in adult and pediatric activation maps may reflect age dependent strategies or maturation of cognitive networks. However, there are important physiologic and anatomic differences in children, varying with age, that may affect the acquisition, analysis, and interpretation of pediatric fMRI data. Differences between children and adult fMRI comparison studies may reflect technical aspects of data acquisition as much as developmental and brain maturation factors.
Introduction
The relationship between language abilities and language lateralization in the developing brain is important for our understanding of the neural architecture of language development.
...Methods
We investigated 35 right‐handed children and adolescents aged 7–16 years with a functional magnetic resonance imaging language paradigm and a comprehensive language and verbal memory examination.
Results
We found that less lateralized language was significantly correlated with better language performance across areas of the brain and across different language tasks. Less lateralized language in the overall brain was associated with better in‐scanner task accuracy on a semantic language decision task and out‐of‐scanner vocabulary and verbal fluency. Specifically, less lateralized frontal lobe language dominance was associated with better in‐scanner task accuracy and out‐of‐scanner verbal fluency. Furthermore, less lateralized parietal language was associated with better out‐of‐scanner verbal memory across learning, short‐ and long‐delay trials. In contrast, we did not find any relationship between temporal lobe language laterality and verbal performance.
Conclusions
This study suggests that semantic language performance is better with some involvement of the nondominant hemisphere.
This study in 35 healthy children and adolescents shows that less lateralized language in the brain is favorable for better language performance.
Characterization of brain–behavior relationships through functional magnetic imaging (fMRI) within typically or atypically developing populations poses methodological and interpretational challenges. ...We consider theoretical, methodological, and artifactual factors that influence characterization of developmental and adaptive changes in childhood. Findings from anatomical and physiological brain development studies are highlighted as they may influence functional imaging results. Then, we consider several patterns of functional activation within the context of developmental processes as well as neurologic disease. Hypotheses regarding the development of cognitive networks are proposed to account for the individual differences seen in normal and atypical development. We also identify potential sources of unwanted variability related to experimental design and task performance and suggest possible solutions to help minimize these effects. Lastly, a challenge for current studies is a lack of group and individual analysis methods that can be reliably applied to capture and quantify factors that contribute to variability introduced by developmental and disease processes. We review current methods and propose potential solutions.
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