Marisa N. Spann

Dynamic Time Course of Typical Childhood Absence Seizures: EEG, Behavior, and Functional Magnetic Resonance Imaging

Absence seizures are 5–10 s episodes of impaired consciousness accompanied by 3–4 Hz generalized spike-and-wave discharge on electroencephalography (EEG). The time course of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG–fMRI in 88 typical childhood absence seizures from nine pediatric patients. We investigated behavior concurrently using a continuous performance task or simpler repetitive tapping task. EEG time–frequency analysis revealed abrupt onset and end of 3–4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex >5 s before seizure onset, followed by profound fMRI decreases continuing >20 s after seizure end. This time course differed markedly from the hemodynamic response function (HRF) model used in conventional fMRI analysis, consisting of large increases beginning after electrical event onset, followed by small fMRI decreases. Other regions, such as the lateral frontal cortex, showed more balanced fMRI increases followed by approximately equal decreases. The thalamus showed delayed increases after seizure onset followed by small decreases, most closely resembling the HRF model. These findings reveal a complex and long-lasting sequence of fMRI changes in absence seizures, which are not detectable by conventional HRF modeling in many regions. These results may be important mechanistically for seizure initiation and termination and may also contribute to changes in EEG and behavior.Absence seizures are 5–10 second episodes of impaired consciousness accompanied by 3–4Hz generalized spike-and-wave discharge on electroencephalography (EEG). The timecourse of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG-fMRI in 88 typical childhood absence seizures from 9 pediatric patients. We investigated behavior concurrently using a continuous performance task (CPT) or simpler repetitive tapping task (RTT). EEG time-frequency analysis revealed abrupt onset and end of 3–4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex >5s before seizure onset, followed by profound fMRI decreases continuing >20s after seizure end. This timecourse differed markedly from the hemodynamic response function (HRF) model used in conventional fMRI analysis, consisting of large increases beginning after electrical event onset, followed by small fMRI decreases. Other regions, such as the lateral frontal cortex, showed more balanced fMRI increases followed by approximately equal decreases. The thalamus showed delayed increases after seizure onset followed by small decreases, most closely resembling the HRF model. These findings reveal a complex and long lasting sequence of fMRI changes in absence seizures, which are not detectible by conventional HRF modeling in many regions. These results may be important mechanistically for seizure initiation and termination and may also contribute to changes in EEG and behavior.

Simultaneous EEG, fMRI, and behavior in typical childhood absence seizures

Purpose:  Absence seizures cause transient impairment of consciousness. Typical absence seizures occur in children, and are accompanied by 3–4‐Hz spike–wave discharges (SWDs) on electroencephalography (EEG). Prior EEG–functional magnetic resonance imaging (fMRI) studies of SWDs have shown a network of cortical and subcortical changes during these electrical events. However, fMRI during typical childhood absence seizures with confirmed impaired consciousness has not been previously investigated.

Childhood abuse and neglect and cognitive flexibility in adolescents

Childhood maltreatment (CM) has been associated with diminished executive functioning in children and adults; however, there is a relative paucity of study of executive function in adolescents exposed to CM. Yet, executive dysfunction in adolescence may have important adverse consequences including increased vulnerability to risky behaviors and impaired school functioning. This study investigates the relationship between self-reported CM and an executive function, cognitive flexibility, in adolescents without identified psychiatric disorders. Effects of physical and emotional, abuse and neglect, maltreatment subtypes were explored. Thirty adolescents ages 12–17 years, 50% females, completed the retrospective self-report Childhood Trauma Questionnaire (CTQ) and were administered the Wisconsin Card Sorting Test (WCST). Correlational analyses assessed the relationship between WCST perseverative error scores norm-referenced for age and education with CTQ total scores. The relationship with nonperseverative errors, as well as with physical and emotional abuse and neglect CM subscores, were explored. Total CTQ scores showed significant associations with perseverative errors on the WCST, but not with nonperseverative errors. Significant associations with perseverative errors were seen for physical abuse and physical neglect among the CTQ subscales. The results suggest both physical abuse and physical neglect are associated with diminished cognitive flexibility in adolescents. These effects were detected in adolescents without identified psychiatric diagnoses suggesting the importance of considering executive dysfunction in adolescents exposed to CM who may not meet diagnostic criteria for an Axis I disorder and that tests of perseverative errors, such as those of the WCST, may be sensitive indicators of this dysfunction.

Symptoms of anxiety and depression in childhood absence epilepsy.

Childhood absence epilepsy (CAE) has been recently linked to a number of cognitive, behavioral, and emotional disorders. Identification of affective disorders (anxiety and depression) presents unique challenges in pediatric populations, and successful early intervention may significantly improve long‐term developmental outcomes. The current study examined the specific anxiety and depression symptoms children with CAE experience, and explored the role of disease factors in the severity of their presentation. Forty‐five subjects with CAE and 41 healthy matched controls, ages 6–16 years, participated in the study. The Behavior Assessment System for Children (BASC) was completed by parents, and the Anxiety and Depression subscales were used to characterize problems. Item analysis within the subscales revealed that children with CAE demonstrated higher rates of symptoms of anxiety (nervousness and thought rumination) and depression (sadness and crying), as well as more general psychosocial problems including isolation and low self‐esteem. Disease duration, intractability, and medication effects were not associated with higher rates of affective problems in this limited patient sample. Screening of patients with CAE for comorbid psychiatric disorders early by focusing on specific symptom profiles unique to this population may enhance overall treatment and developmental outcomes.

Differentiation of attention-related problems in childhood absence epilepsy

The current study examined the specific types of attention-related problems children with childhood absence epilepsy (CAE) experience and the role of disease factors in the development of attention-related problems. Thirty-eight subjects with CAE and 46 healthy controls, aged 6 to 16, participated in the study. The Behavior Assessment System for Children (BASC) was completed by parents, and the Attention Problems and Hyperactivity subscales were used to characterize the problems of children with CAE. Item analysis within the subscales revealed that children with CAE demonstrate higher rates of hyperactive (overactivity and fidgetiness) and inattentive (forgetfulness and distractibility) problems, and require more supervision. Within-CAE-group analyses revealed that those who were actively having seizures were more impatient and those with a longer duration of illness were less proficient in completing homework. Children with CAE are at risk for certain inattentive and hyperactive problems, which can differ depending on duration of illness and active seizure status.

Influences on the Test–Retest Reliability of Functional Connectivity MRI and its Relationship with Behavioral Utility

Abstract Best practices are currently being developed for the acquisition and processing of resting‐state magnetic resonance imaging data used to estimate brain functional organization—or “functional connectivity.” Standards have been proposed based on test‐retest reliability, but open questions remain. These include how amount of data per subject influences whole‐brain reliability, the influence of increasing runs versus sessions, the spatial distribution of reliability, the reliability of multivariate methods, and, crucially, how reliability maps onto prediction of behavior. We collected a dataset of 12 extensively sampled individuals (144 min data each across 2 identically configured scanners) to assess test‐retest reliability of whole‐brain connectivity within the generalizability theory framework. We used Human Connectome Project data to replicate these analyses and relate reliability to behavioral prediction. Overall, the historical 5‐min scan produced poor reliability averaged across connections. Increasing the number of sessions was more beneficial than increasing runs. Reliability was lowest for subcortical connections and highest for within‐network cortical connections. Multivariate reliability was greater than univariate. Finally, reliability could not be used to improve prediction; these findings are among the first to underscore this distinction for functional connectivity. A comprehensive understanding of test‐retest reliability, including its limitations, supports the development of best practices in the field.

Structure-function associations in hippocampus in bipolar disorder.

Hippocampus volume decreases and verbal memory deficits have been reported in bipolar disorder (BD) as independent observations. We investigated potential associations between these deficits in subjects with BD. Hippocampus volumes were measured on magnetic resonance images of 31 subjects with BD and 32 healthy comparison (HC) subjects. The California Verbal Learning Test-Second Edition (CVLT) assessed verbal memory function in these subjects. Compared to the HC group, the BD group showed both significantly smaller hippocampus volumes and impaired performance on CVLT tests of immediate, short delay and long delay cued and free recall. Further, smaller hippocampus volume correlated with impaired performance in BD. Post hoc analyses revealed a trend towards improved memory in BD subjects taking antidepressant medications. These results support associations between morphological changes in hippocampus structure in BD and verbal memory impairment. They provide preliminary evidence pharmacotherapy may reverse hippocampus-related memory deficits.

Consequence of Preterm Birth in Early Adolescence: The Role of Language on Auditory Short-term Memory

This study tested the hypothesis that preterm early adolescents’ short-term memory is compromised when presented with increasingly complex verbal information and that associated neuroanatomical volumes would differ between preterm and term groups. Forty-nine preterm and 20 term subjects were evaluated at age 12 years with neuropsychological measures and magnetic resonance imaging (MRI). There were no differences between groups in simple short-term and working memory. Preterm subjects performed lower on learning and short-term memory tests that included increased verbal complexity. They had reduced right parietal, left temporal, and right temporal white matter volumes and greater bilateral frontal gray and right frontal white matter volumes. There was a positive association between complex working memory and the left hippocampus and frontal white matter in term subjects. While not correlated, memory scores and volumes of cortical regions known to subserve language and memory were reduced in preterm subjects. This study provides evidence of possible mechanisms for learning problems in former preterm infants.

Summary of the update session on clinical neurotoxicity studies

During the Fifth Pediatric Anesthesia Neurodevelopmental Assessment Symposium, experts and stakeholders met to present and discuss recent advances made in the study of neurodevelopmental outcomes after exposure to anesthetic drugs in infants and children. This article summarizes the update of 5 ongoing clinical studies: General Anesthesia compared to Spinal Anesthesia, Toxicity of Remifentanil and Dexmedetomidine, Mayo Anesthesia Safety in Kids, the University of California San Francisco human cohort study, and Columbia University Medical Center Neonatal Magnetic Resonance Imaging study. The purpose of this summary is to discuss the contributions and limitations of these studies, how they fit into the published literature, and what questions remain to be answered.

Morphological features of the neonatal brain support development of subsequent cognitive, language, and motor abilities.

Knowledge of the role of brain maturation in the development of cognitive abilities derives primarily from studies of school‐age children to adults. Little is known about the morphological features of the neonatal brain that support the subsequent development of abilities in early childhood, when maturation of the brain and these abilities are the most dynamic. The goal of our study was to determine whether brain morphology during the neonatal period supports early cognitive development through 2 years of age. We correlated morphological features of the cerebral surface assessed using deformation‐based measures (surface distances) of high‐resolution MRI scans for 33 healthy neonates, scanned between the first to sixth week of postmenstrual life, with subsequent measures of their motor, language, and cognitive abilities at ages 6, 12, 18, and 24 months. We found that morphological features of the cerebral surface of the frontal, mesial prefrontal, temporal, and occipital regions correlated with subsequent motor scores, posterior parietal regions correlated with subsequent language scores, and temporal and occipital regions correlated with subsequent cognitive scores. Measures of the anterior and middle portions of the cingulate gyrus correlated with scores across all three domains of ability. Most of the significant findings were inverse correlations located bilaterally in the brain. The inverse correlations may suggest either that a more protracted morphological maturation or smaller local volumes of neonatal brain tissue supports better performance on measures of subsequent motor, language, and cognitive abilities throughout the first 2 years of postnatal life. The correlations of morphological measures of the cingulate with measures of performance across all domains of ability suggest that the cingulate supports a broad range of skills in infancy and early childhood, similar to its functions in older children and adults. Hum Brain Mapp 35:4459–4474, 2014.