Publications by authors named "Leigh Sepeta"

19 Publications

  • Page 1 of 1

Functional connectivity hemispheric contrast (FC-HC): A new metric for language mapping.

Neuroimage Clin 2021 Mar 1:102598. Epub 2021 Mar 1.

Department of Neurology, Children's National Hospital, 111 Michigan Ave NW, Washington, DC 20010, United States. Electronic address:

Development of a task-free method for presurgical mapping of language function is important for use in young or cognitively impaired patients. Resting state connectivity fMRI (RS-fMRI) is a task-free method that may be used to identify cognitive networks. We developed a voxelwise RS-fMRI metric, Functional Connectivity Hemispheric Contrast (FC-HC), to map the language network and determine language laterality through comparison of within-hemispheric language network connections (Integration) to cross-hemispheric connections (Segregation). For the first time, we demonstrated robustness and efficacy of a RS-fMRI metric to map language networks across five groups (total N = 243) that differed in MRI scanning parameters, fMRI scanning protocols, age, and development (typical vs pediatric epilepsy). The resting state FC-HC maps for the healthy pediatric and adult groups showed higher values in the left hemisphere, and had high agreement with standard task language fMRI; in contrast, the epilepsy patient group map was bilateral. FC-HC has strong but not perfect agreement with task fMRI and thus, may reflect related and complementary information about language plasticity and compensation.
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http://dx.doi.org/10.1016/j.nicl.2021.102598DOI Listing
March 2021

Cortical thickness in childhood left focal epilepsy: Thinning beyond the seizure focus.

Epilepsy Behav 2020 01 6;102:106825. Epub 2019 Dec 6.

Comprehensive Pediatric Epilepsy Program, Children's National Medical Center, Washington, DC, USA; Department of Psychiatry and Behavioral Sciences, The George Washington University, Washington, DC, USA. Electronic address:

Objective: Structural brain differences are found in adults and children with epilepsy, yet pediatric samples have been heterogeneous regarding seizure type, magnetic resonance imaging (MRI) findings, and hemisphere of seizure focus. This study examines whether cortical thickness and surface area differ between children with left-hemisphere focal epilepsy (LHE) and age-matched typically developing (TD) peers. We examined whether age differentially moderated cortical thickness between groups and if cortical thickness was associated with duration of epilepsy, seizure frequency, or neuropsychological functioning.

Methods: Thirty-five children with LHE and 35 TD children completed neuropsychological testing and 3T MR imaging. Neuropsychological measures included general intelligence and executive functioning. All MRIs were normal. Surface-based morphometric processing and analyses were conducted using FreeSurfer 6.0. Regression analyses compared age by cortical thickness differences between groups. Correlational analyses examined associations between cortical thickness in these areas with neuropsychological functioning or epilepsy characteristics.

Results: Left-hemisphere focal epilepsy displayed decreased cortical thickness bilaterally compared to TD controls across 6 brain regions but no differences in surface area. Moderation analyses revealed quadratic relationships between age and cortical thickness for left frontoparietal-cingulate and right superior frontal regions. Higher performance intelligence quotient (IQ) (PIQ) and verbal IQ (VIQ) and fewer parent reported executive function problems were associated with greater cortical thickness in TD children.

Significance: Children with LHE displayed thinner cortex extending beyond the hemisphere of seizure focus. The nonlinear pattern of cortical thickness across age occurring in TD children is not evident in the same manner in children with LHE. These differences in cortical thickness patterns were greatest in children 8-12 years old. Greater cortical thickness was associated with higher IQ and fewer executive control problems in daily activities in TD children. Thus, differences in cortical thickness in the absence of differences in surface area, suggest cortical thickness may be a sensitive proxy of subtle neuroanatomical changes that are related to neuropsychological functioning.
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http://dx.doi.org/10.1016/j.yebeh.2019.106825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962541PMC
January 2020

Functional MRI and direct cortical stimulation: Prediction of postoperative language decline.

Epilepsia 2019 03 11;60(3):560-570. Epub 2019 Feb 11.

Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.

Objective: To assess the ability of functional MRI (fMRI) to predict postoperative language decline compared to direct cortical stimulation (DCS) in epilepsy surgery patients.

Methods: In this prospective case series, 17 patients with drug-resistant epilepsy had intracranial monitoring and resection from 2012 to 2016 with 1-year follow-up. All patients completed preoperative language fMRI, mapping with DCS of subdural electrodes, pre- and postoperative neuropsychological testing for language function, and resection. Changes in language function before and after surgery were assessed. fMRI activation and DCS electrodes in the resection were evaluated as potential predictors of language decline.

Results: Four of 17 patients (12 female; median [range] age, 43 [23-59] years) experienced postoperative language decline 1 year after surgery. Two of 4 patients had overlap of fMRI activation, language-positive electrodes in basal temporal regions (within 1 cm), and resection. Two had overlap between resection volume and fMRI activation, but not DCS. fMRI demonstrated 100% sensitivity and 46% specificity for outcome compared to DCS (50% and 85%, respectively). When fMRI and DCS language findings were concordant, the combined tests showed 100% sensitivity and 75% specificity for language outcome. Seizure-onset age, resection side, type, volume, or 1 year seizure outcome did not predict language decline.

Significance: Language localization overlap of fMRI and direct cortical stimulation in the resection influences postoperative language performance. Our preliminary study suggests that fMRI may be more sensitive and less specific than direct cortical stimulation. Together they may predict outcome better than either test alone.
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http://dx.doi.org/10.1111/epi.14666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467056PMC
March 2019

fMRI prediction of naming change after adult temporal lobe epilepsy surgery: Activation matters.

Epilepsia 2019 03 11;60(3):527-538. Epub 2019 Feb 11.

Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.

Objective: We aimed to predict language deficits after epilepsy surgery. In addition to evaluating surgical factors examined previously, we determined the impact of the extent of functional magnetic resonance imaging (fMRI) activation that was resected on naming ability.

Method: Thirty-five adults (mean age 37.5 ± 10.9 years, 13 male) with temporal lobe epilepsy completed a preoperative fMRI auditory description decision task, which reliably activates frontal and temporal language networks. Patients underwent temporal lobe resections (20 left resection). The Boston Naming Test (BNT) was used to determine language functioning before and after surgery. Language dominance was determined for Broca and Wernicke area (WA) by calculating a laterality index following statistical parametric mapping processing. We used an innovative method to generate anatomic resection masks automatically from pre- and postoperative MRI tissue map comparison. This mask provided the following: (a) resection volume; (b) overlap between resection and preoperative activation; and (c) overlap between resection and WA. We examined postoperative language change predictors using stepwise linear regression. Predictors included parameters described above as well as age at seizure onset (ASO), preoperative BNT score, and resection side and its relationship to language dominance.

Results: Seven of 35 adults had significant naming decline (6 dominant-side resections). The final regression model predicted 38% of the naming score change variance (adjusted r = 0.28, P = 0.012). The percentage of top 10% fMRI activation resected (P = 0.017) was the most significant contributor. Other factors in the model included WA LI, ASO, volume of WA resected, and WA LI absolute value (extent of laterality).

Significance: Resection of fMRI activation during a word-definition decision task is an important factor for postoperative change in naming ability, along with other previously reported predictors. Currently, many centers establish language dominance using fMRI. Our results suggest that the amount of the top 10% of language fMRI activation in the intended resection area provides additional predictive power and should be considered when planning surgical resection.
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http://dx.doi.org/10.1111/epi.14656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401285PMC
March 2019

Imaging episodic memory during development and childhood epilepsy.

J Neurodev Disord 2018 12 13;10(1):40. Epub 2018 Dec 13.

Center for Neuroscience Research, Children's National Medical Center, 111 Michigan Avenue NW, Washington, D.C., 20010, USA.

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.
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http://dx.doi.org/10.1186/s11689-018-9255-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292091PMC
December 2018

Everyday executive function in focal onset pediatric epilepsy on the parent-report BRIEF2.

Child Neuropsychol 2019 01 29;25(1):22-43. Epub 2018 Jan 29.

a Division of Pediatric Neuropsychology , Children's National Medical Center , Washington , DC , USA.

Executive function (EF) difficulties are a core neuropsychological feature of pediatric epilepsy, and parent-report measures of EF concerns are an important complement to task-based EF measures. The Behavior Rating Inventory of Executive Function (BRIEF) has shown sensitivity to parent-reported EF concerns in epilepsy and other pediatric populations. We compared profiles of parent-reported EF concerns using the BRIEF and its revision, the BRIEF2, in 117 pediatric patients with focal onset epilepsy to examine the clinical utility of the revised scale. We then compared BRIEF2 profiles between patients and age- and gender-matched healthy controls. Among patients, profiles on the BRIEF did not globally differ from the BRIEF2, and agreement was very good across scales. Patients and controls differed significantly on the BRIEF2, with patients showing higher EF difficulties reported by parents across most scales. High rates of clinical elevation among patients emerged on the Task Monitor, Plan/Organize, Working Memory, and Shift scales. Younger age of epilepsy onset, chronic epilepsy, and right hemisphere seizure focus were associated with higher parent-reported EF concerns. Findings suggest that the BRIEF2 demonstrates similar performance to the BRIEF among pediatric patients with focal onset epilepsy who are most at risk in the areas of task monitoring, working memory, planning and organization, and flexibility. These findings are informative when comparing literature across versions and provide additional insight into the nature of parent-reported EF difficulties among children with focal onset epilepsy.
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http://dx.doi.org/10.1080/09297049.2018.1424326DOI Listing
January 2019

Language functional MRI and direct cortical stimulation in epilepsy preoperative planning.

Ann Neurol 2017 Apr 22;81(4):526-537. Epub 2017 Mar 22.

Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD.

Objective: Presurgical language assessment can help minimize damage to eloquent cortex during resective epilepsy surgery. Two methods for presurgical language mapping are functional MRI (fMRI) and direct cortical stimulation (DCS) of implanted subdural electrodes. We compared fMRI results to DCS to help optimize noninvasive language localization and assess its validity.

Methods: We studied 19 patients referred for presurgical evaluation of drug-resistant epilepsy. Patients completed four language tasks during preoperative fMRI. After subdural electrode implantation, we used DCS to localize language areas. For each stimulation site, we determined whether language positive electrode pairs intersected with significant fMRI activity clusters for language tasks.

Results: Sensitivity and specificity depended on electrode region of interest radii and statistical thresholding. For patients with at least one language positive stimulation site, an auditory description decision task provided the best trade-off between sensitivity and specificity. For patients with no language positive stimulation sites, fMRI was a dependable method of excluding eloquent language processing.

Interpretation: Language fMRI is an effective tool for determining language lateralization before electrode implantation and is especially useful for excluding unexpected critical language areas. It can help guide subdural electrode implantation and narrow the search for eloquent cortical areas by DCS. Ann Neurol 2017;81:526-537.
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http://dx.doi.org/10.1002/ana.24899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5401636PMC
April 2017

The role of executive functioning in memory performance in pediatric focal epilepsy.

Epilepsia 2017 02 23;58(2):300-310. Epub 2017 Jan 23.

Department of Neurosciences, Children's National Health System, Washington, District of Columbia, U.S.A.

Objective: Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population.

Methods: Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (Wechsler Abbreviated Scale of Intelligence [WASI]/Differential Ability Scales [DAS]), as well as visual Children's Memory Scale (CMS Dot Locations) and verbal episodic memory (Wide Range Assessment of Memory and Learning [WRAML] Story Memory and California Verbal Learning Test for Children [CVLT-C]). Executive functioning was measured directly (WISC-IV Digit Span Backward; Clinical Evaluation of Language Fundamentals, Fourth Edition (CELF-IV) Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function [BRIEF]).

Results: Children with focal epilepsy had lower delayed free-recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η = 0.12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η = 0.03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η = 0.08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9-19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9-10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extratemporal, frontal vs. extrafrontal).

Significance: Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization. Executive functioning accounted for significant variance in memory performance, suggesting that poor executive control negatively influences memory retrieval.
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http://dx.doi.org/10.1111/epi.13637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300699PMC
February 2017

Temporal lobe epilepsy and focal cortical dysplasia in children: A tip to find the abnormality.

Epilepsia 2017 01 16;58(1):113-122. Epub 2016 Nov 16.

Center for Neuroscience, Children's National Health System, George Washington University, Washington, District of Columbia, U.S.A.

Objective: To demonstrate an association between magnetic resonance imaging (MRI) findings and pathologic characteristics in children who had surgery for medically refractory epilepsy due to focal cortical dysplasia (FCD).

Methods: We retrospectively studied 110 children who had epilepsy surgery. Twenty-seven patients with FCD were included. Thirteen had temporal lobe epilepsy (TLE) and 14 had extra-temporal lobe epilepsy (ETLE). Three patients had associated mesial temporal sclerosis. Preoperative 3T MRIs interleaved with nine controls were blindly re-reviewed and categorized according to signal alteration. Pathologic specimens were classified according to the 2011 International League Against Epilepsy (ILAE) classification and compared to MRI studies.

Results: Rates of pathology subtypes differed between TLE and ETLE (χ (3) = 8.57, p = 0.04). FCD type I was more frequent in TLE, whereas FCD type II was more frequent in ETLE. In the TLE group, nine patients had temporal tip abnormalities. They all exhibited gray-white matter blurring with decreased myelination and white matter hyperintense signal. Blurring involved the whole temporal tip, not just the area of dysplasia. These patients were less likely to demonstrate cortical thickening compared to those without temporal tip findings (χ (1) = 9.55, p = 0.002). Three of them had FCD Ib, three had FCD IIa, two had FCD IIIa, and one had FCD IIb; MRI features could not entirely distinguish between FCD subtypes. TLE patients showed more pronounced findings than ETLE on MRI (χ (1) = 11.95, p = 0.003, odds ratio [OR] 18.00). In all cases of FCD, isolated blurring was more likely to be associated with FCD II, whereas blurring with decreased myelination was seen with FCD I (χ (6) = 13.07, p = 0.042).

Significance: Our study described associations between MRI characteristics and pathology in children with FCD and offered a detailed analysis of temporal lobe tip abnormalities and FCD subtypes in children with TLE. These findings may contribute to the presurgical evaluation of patients with refractory epilepsy.
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http://dx.doi.org/10.1111/epi.13615DOI Listing
January 2017

Age-dependent mesial temporal lobe lateralization in language fMRI.

Epilepsia 2016 Jan 23;57(1):122-30. Epub 2015 Dec 23.

Children's National Health System, Washington, District of Columbia, U.S.A.

Objective: Functional magnetic resonance imaging (fMRI) activation of the mesial temporal lobe (MTL) may be important for epilepsy surgical planning. We examined MTL activation and lateralization during language fMRI in children and adults with focal epilepsy.

Methods: One hundred forty-two controls and patients with left hemisphere focal epilepsy (pediatric: epilepsy, n = 17, mean age = 9.9 ± 2.0; controls, n = 48; mean age = 9.1 ± 2.6; adult: epilepsy, n = 20, mean age = 26.7 ± 5.8; controls, n = 57, mean age = 26.2 ± 7.5) underwent 3T fMRI using a language task (auditory description decision task). Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8); regions of interest (ROIs) included MTL, Broca's area, and Wernicke's area. We assessed group and individual MTL activation, and examined degree of lateralization.

Results: Patients and controls (pediatric and adult) demonstrated group and individual MTL activation during language fMRI. MTL activation was left lateralized for adults, but less so in children (p's < 0.005). Patients did not differ from controls in either age group. Stronger left-lateralized MTL activation was related to older age (p = 0.02). Language lateralization (Broca's and Wernicke's) predicted 19% of the variance in MTL lateralization for adults (p = 0.001), but for not children.

Significance: Language fMRI may be used to elicit group and individual MTL activation. The developmental difference in MTL lateralization and its association with language lateralization suggests a developmental shift in lateralization of MTL function, with increased left lateralization across the age span. This shift may help explain why children have better memory outcomes following resection compared to adults.
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http://dx.doi.org/10.1111/epi.13258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749038PMC
January 2016

Speed and complexity characterize attention problems in children with localization-related epilepsy.

Epilepsia 2015 Jun 4;56(6):833-40. Epub 2015 May 4.

Children's National Health System (CNHS), Washington, District of Columbia, U.S.A.

Objective: Children with epilepsy (EPI) have a higher rate of attention-deficit/hyperactivity disorder (ADHD; 28-70%) than typically developing (TD) children (5-10%); however, attention is multidimensional. Thus, we aimed to characterize the profile of attention difficulties in children with epilepsy.

Methods: Seventy-five children with localization-related epilepsy ages 6-16 years and 75 age-matched controls were evaluated using multimodal, multidimensional measures of attention including direct performance and parent ratings of attention as well as intelligence testing. We assessed group differences across attention measures, determined if parent rating predicted performance on attention measures, and examined if epilepsy characteristics were associated with attention skills.

Results: The EPI group performed worse than the TD group on timed and complex attention aspects of attention (p < 0.05), whereas performance on simple visual and simple auditory attention tasks was comparable. Children with EPI were 12 times as likely as TD children to have clinically elevated symptoms of inattention as rated by parents, but ratings were a weak predictor of attention performance. Earlier age of onset was associated with slower motor speed (p < 0.01), but no other epilepsy-related clinical characteristics were associated with attention skills.

Significance: This study clarifies the nature of the attention problems in pediatric epilepsy, which may be under-recognized. Children with EPI had difficulty with complex attention and rapid response, not simple attention. As such, they may not exhibit difficulty until later in primary school when demands increase. Parent report with standard ADHD screening tools may under-detect these higher-order attention difficulties. Thus, monitoring through direct neuropsychological performance is recommended.
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http://dx.doi.org/10.1111/epi.12985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457628PMC
June 2015

Reduced language connectivity in pediatric epilepsy.

Epilepsia 2015 Feb 17;56(2):273-82. Epub 2014 Dec 17.

Children's National Medical Center, Washington, District of Columbia, U.S.A.

Objective: Functional connectivity (FC) among language regions is decreased in adults with epilepsy compared to controls, but less is known about FC in children with epilepsy. We sought to determine if language FC is reduced in pediatric epilepsy, and examined clinical factors that associate with language FC in this population.

Methods: We assessed FC during an age-adjusted language task in children with left-hemisphere focal epilepsy (n = 19) compared to controls (n = 19). Time series data were extracted for three left regions of interest (ROIS) and their right homologues: inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and Wernicke's area (WA) using SPM8. Associations between FC and factors such as cognitive performance, language dominance, and epilepsy duration were assessed.

Results: Children with epilepsy showed decreased interhemispheric connectivity compared to controls, particularly between core left language regions (IFG, WA) and their right hemisphere homologues, as well as decreased intrahemispheric right frontal FC. Increased intrahemispheric FC between left IFG and left WA was a positive predictor of language skills overall, and naming ability in particular. FC of language areas was not affected by language dominance, as the effects remained only when examining participants with left language dominance. Overall FC did not differ according to duration of epilepsy or age of onset.

Significance: FC during a language task is reduced in children, similar to findings in adults. In specific, children with left focal epilepsy demonstrated decreased interhemispheric FC in temporal and frontal language connections and decreased intrahemispheric right frontal FC. These differences were present near the onset of epilepsy. Greater FC between left language centers is related to better language ability. Our results highlight that connectivity of language areas has a developmental pattern and is related to cognitive ability.
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http://dx.doi.org/10.1111/epi.12859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340750PMC
February 2015

Vulnerability of the ventral language network in children with focal epilepsy.

Brain 2014 Aug 17;137(Pt 8):2245-57. Epub 2014 Jun 17.

1 Institute of Child Health, University College London, London, UK1 Institute of Child Health, University College London, London, UK.

Children with focal epilepsy are at increased risk of language impairment, yet the neural substrate of this dysfunction is not yet known. Using functional magnetic resonance imaging we investigated the impact of focal epilepsy on the developing language system using measures of network topology (spatial organization of activation) and synchrony (functional connectivity). We studied healthy children (n = 48, 4-12 years, 24 females) and children with focal epilepsy (n = 21, 5-12 years, nine females) with left hemisphere language dominance. Participants performed an age-adjusted auditory description decision task during functional magnetic resonance imaging, to identify perisylvian language regions. Mean signal change was extracted from eight left perisylvian regions of interest and compared between groups. Paired region of interest functional connectivity analysis was performed on time course data from the same regions, to investigate left network synchrony. Two principal component analyses were performed to extract (i) patterns of activation (using mean signal change data); and (ii) patterns of synchronized regions (using functional connectivity data). For both principal component analyses two components (networks) were extracted, which mapped onto the functional anatomy of dorsal and ventral language systems. Associations among network variables, age, epilepsy-related factors and verbal ability were assessed. Activated networks were affected by age and epilepsy [F(2,60) = 3.74, P = 0.03]: post hoc analyses showed, for healthy children, activation in both ventral and dorsal networks decreased with age (P = 0.02). Regardless of age and task performance, children with epilepsy showed reduced activation of the ventral network (P < 0.001). They also showed a trend for increased activation of the dorsal network (P = 0.08) associated with improved task performance (r = 0.62, P = 0.008). Crucially, decreased activation of the ventral network in patients predicted poorer language outcome ([Formula: see text] = 0.47, P = 0.002). This suggests childhood onset epilepsy preferentially alters maturation of the ventral language system, and this is related to poorer language ability.
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http://dx.doi.org/10.1093/brain/awu154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107744PMC
August 2014

Watch the hands: infants can learn to follow gaze by seeing adults manipulate objects.

Dev Sci 2014 Mar 4;17(2):270-81. Epub 2014 Jan 4.

Department of Cognitive Science, University of California at San Diego, USA.

Infants gradually learn to share attention, but it is unknown how they acquire skills such as gaze-following. Deák and Triesch (2006) suggest that gaze-following could be acquired if infants learn that adults' gaze direction is likely to be aligned with interesting sights. This hypothesis stipulates that adults tend to look at things that infants find interesting, and that infants could learn by noticing this tendency. We tested the plausibility of this hypothesis through video-based micro-behavioral analysis of naturalistic parent-infant play. The results revealed that 3- to 11-month-old infants strongly preferred watching caregivers handle objects. In addition, when caregivers looked away from their infant they tended to look at their own object-handling. Finally, when infants looked toward the caregiver while she was looking at her own hands, the infant's next eye movement was often toward the caregiver's object-handling. In this way infants receive adequate naturalistic input to learn associations between their parent's gaze direction and the locations of interesting sights.
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http://dx.doi.org/10.1111/desc.12122DOI Listing
March 2014

Functional status of children with encephalitis in an inpatient rehabilitation setting: a case series.

J Pediatr Rehabil Med 2013 ;6(3):163-73

Department of Physical Medicine and Rehabilitation, Sinai Hospital of Baltimore, Baltimore, MD, USA.

Introduction: Patterns and predictors of recovery from encephalitis are poorly understood.

Methods: This study examined functional status and reviewed charts of all children who presented to a pediatric inpatient rehabilitation facility with encephalitis between 1996 and 2010. Functional status at admission and discharge from inpatient rehabilitation was evaluated using the Functional Independence Measure for Children (WeeFIM) Self-care, Mobility, Cognitive, and Total Developmental Functional Quotient scores (DFQ, % of age-appropriate function). Charts were reviewed to characterize key clinical features and findings.

Results: Of the 13 children identified, the mean age was 9 years (range 5-16) with 54% males. Mean WeeFIM Total DFQ at admission was 37 (range: 15-90) and at discharge was 64 (range: 16-96). Average change in WeeFIM Total DFQ from admission to discharge was 26.7 (range 0-55, p < 0.001). WeeFIM domain scores improved between admission and discharge (Self-Care: p < 0.001, Cognition: p < 0.01, Mobility: p < 0.001). Eleven children displayed significant impairments in functional skills, defined as DFQ of < or =85, at discharge. Key clinical features and findings were diverse and not related to functional outcome.

Conclusions: Results suggest that significant functional improvement in children with encephalitis occurs during inpatient rehabilitation. Further research is necessary to identify predictors of outcome in children with encephalitis.
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http://dx.doi.org/10.3233/PRM-130248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114105PMC
July 2014

Characterization of atypical language activation patterns in focal epilepsy.

Ann Neurol 2014 Jan 2;75(1):33-42. Epub 2014 Jan 2.

Pediatric Imaging and Tissue Sciences Section on Tissue Biophysics and Biomimetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; Center for Neuroscience Research, Children's National Medical Center, George Washington University, Washington, DC.

Objective: Functional magnetic resonance imaging is sensitive to the variation in language network patterns. Large populations are needed to rigorously assess atypical patterns, which, even in neurological populations, are a minority.

Methods: We studied 220 patients with focal epilepsy and 118 healthy volunteers who performed an auditory description decision task. We compared a data-driven hierarchical clustering approach to the commonly used a priori laterality index (LI) threshold (LI < 0.20 as atypical) to classify language patterns within frontal and temporal regions of interest. We explored (n = 128) whether IQ varied with different language activation patterns.

Results: The rate of atypical language among healthy volunteers (2.5%) and patients (24.5%) agreed with previous studies; however, we found 6 patterns of atypical language: a symmetrically bilateral, 2 unilaterally crossed, and 3 right dominant patterns. There was high agreement between classification methods, yet the cluster analysis revealed novel correlations with clinical features. Beyond the established association of left-handedness, early seizure onset, and vascular pathology with atypical language, cluster analysis identified an association of handedness with frontal lateralization, early seizure onset with temporal lateralization, and left hemisphere focus with a unilateral right pattern. Intelligence quotient was not significantly different among patterns.

Interpretation: Language dominance is a continuum; however, our results demonstrate meaningful thresholds in classifying laterality. Atypical language patterns are less frequent but more variable than typical language patterns, posing challenges for accurate presurgical planning. Language dominance should be assessed on a regional rather than hemispheric basis, and clinical characteristics should inform evaluation of atypical language dominance. Reorganization of language is not uniformly detrimental to language functioning.
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http://dx.doi.org/10.1002/ana.24015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209919PMC
January 2014

Abnormal social reward processing in autism as indexed by pupillary responses to happy faces.

J Neurodev Disord 2012 Jun 7;4(1):17. Epub 2012 Jun 7.

Ahmanson-Lovelace Brain Mapping Center, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, 90095, USA.

Background: Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding.

Methods: We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects.

Results: Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group.

Conclusions: We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli.
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http://dx.doi.org/10.1186/1866-1955-4-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461481PMC
June 2012

Neural bases of gaze and emotion processing in children with autism spectrum disorders.

Brain Behav 2011 Sep;1(1):1-11

Abnormal eye contact is a core symptom of autism spectrum disorders (ASD), though little is understood of the neural bases of gaze processing in ASD. Competing hypotheses suggest that individuals with ASD avoid eye contact due to the anxiety-provoking nature of direct eye gaze or that eye-gaze cues hold less interest or significance to children with ASD. The current study examined the effects of gaze direction on neural processing of emotional faces in typically developing (TD) children and those with ASD. While undergoing functional magnetic resonance imaging (fMRI), 16 high-functioning children and adolescents with ASD and 16 TD controls viewed a series of faces depicting emotional expressions with either direct or averted gaze. Children in both groups showed significant activity in visual-processing regions for both direct and averted gaze trials. However, there was a significant group by gaze interaction such that only TD children showed reliably greater activity in ventrolateral prefrontal cortex for direct versus averted gaze. The ASD group showed no difference between direct and averted gaze in response to faces conveying negative emotions. These results highlight the key role of eye gaze in signaling communicative intent and suggest altered processing of the emotional significance of direct gaze in children with ASD.
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http://dx.doi.org/10.1002/brb3.6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217668PMC
September 2011

Early childhood predictors of the social competence of adults with autism.

J Autism Dev Disord 2012 Feb;42(2):161-74

Department of Psychology, University of California, Los Angeles, CA, USA.

Longitudinal research into adult outcomes in autism remains limited. Unlike previous longitudinal examinations of adult outcome in autism, the twenty participants in this study were evaluated across multiple assessments between early childhood (M = 3.9 years) and adulthood (M = 26.6 years). In early childhood, responsiveness to joint attention (RJA), language, and intelligence were assessed. In adulthood, the parents of participants responded to interviews assessing the adaptive functioning, autistic symptomology and global functioning of their children. RJA and early childhood language predicted a composite measure of adult social functioning and independence. Early childhood language skills and intelligence predicted adult adaptive behaviors. RJA predicted adult non-verbal communication, social skills and symptoms. Adaptive behaviors changed with development, but symptoms of autism did not. Additional factors associated with adult outcomes are discussed.
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http://dx.doi.org/10.1007/s10803-011-1222-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265725PMC
February 2012