Thought disorder and frontotemporal volumes in pediatric epilepsy

Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Epilepsy & Behavior (Impact Factor: 2.26). 11/2008; 13(4):593-9. DOI: 10.1016/j.yebeh.2008.06.021
Source: PubMed


The aim of this study was to determine if volumes of frontotemporal regions associated with language were related to thought disorder in 42 children, aged 5-16 years, with cryptogenic epilepsy, all of whom had complex partial seizures (CPS). The children with CPS and 41 age- and gender-matched healthy children underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, and temporal lobe volumes were computed. Thought disorder measures, IQ, and seizure information were collected for each patient. The subjects with CPS had more thought disorder, smaller total gray matter and orbital frontal gray matter volumes, as well as larger temporal lobe white matter volumes than the control group. In the CPS group, thought disorder was significantly related to smaller orbital frontal and inferior frontal gray matter volumes, increased Heschl's gyrus gray matter volumes, and smaller superior temporal gyrus white matter volumes. However, significantly larger orbital frontal gyrus, superior temporal gyrus, and temporal lobe gray matter volumes and decreased Heschl's gyrus white matter volumes were associated with thought disorder in the control group. These findings suggest that thought disorder might represent a developmental disability involving frontotemporal regions associated with language in pediatric CPS.

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Available from: Rochelle Caplan, Dec 13, 2013
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    • "These behavioral, cognitive, linguistic, and social comorbidities can collectively exert a negative effect on daily activities, such as relationships within the family, peer interactions, school performance, and extracurricular activities (Baca et al., 2011). There is now substantial evidence indicating that childhood-onset epilepsy is associated with altered brain development (Hutchinson et al., 2010; Pulsipher et al., 2011; Tosun et al., 2011; Lin et al., 2012) and that these structural abnormalities are linked to neurobehavioral comorbidities (Daley et al., 2007; Caplan et al., 2008; Pulsipher et al., 2009; O'Muircheartaigh et al., 2011; Vollmar et al., 2011; Lin et al., 2012). In healthy growing children, cortical gray matter volume and thickness declines with increasing age (Giedd & Rapoport, 2010). "
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    ABSTRACT: Neurobehavioral comorbidities are common in pediatric epilepsy with enduring adverse effects on functioning, but their neuroanatomic underpinning is unclear. Striatal and thalamic abnormalities have been associated with childhood-onset epilepsies, suggesting that epilepsy-related changes in the subcortical circuit might be associated with the comorbidities of children with epilepsy. We aimed to compare subcortical volumes and their relationship with age in children with complex partial seizures (CPS), childhood absence epilepsy (CAE), and healthy controls (HC). We examined the shared versus unique structural-functional relationships of these volumes with behavior problems, intelligence, language, peer interaction, and epilepsy variables in these two epilepsy syndromes. We investigated volumetric differences of caudate, putamen, pallidum, and thalamus in children with CPS (N = 21), CAE (N = 20), and HC (N = 27). Study subjects underwent structural magnetic resonance imaging (MRI), intelligence, and language testing. Parent-completed Child Behavior Checklists provided behavior problem and peer interaction scores. We examined the association of age, intelligence quotient (IQ), language, behavioral problems, and epilepsy variables with subcortical volumes that were significantly different between the children with epilepsy and HC. Both children with CPS and CAE exhibited significantly smaller left thalamic volume compared to HC. In terms of developmental trajectory, greater thalamic volume was significantly correlated with increasing age in children with CPS and CAE but not in HC. With regard to the comorbidities, reduced left thalamic volumes were related to more social problems in children with CPS and CAE. Smaller left thalamic volumes in children with CPS were also associated with poor attention, lower IQ and language scores, and impaired peer interaction. Our study is the first to directly compare and detect shared thalamic structural abnormalities in children with CPS and CAE. These findings highlight the vulnerability of the thalamus and provide important new insights on its possible role in the neurobehavioral comorbidities of childhood-onset epilepsy.
    Epilepsia 12/2013; 54(12):2116-24. DOI:10.1111/epi.12428 · 4.57 Impact Factor
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    • "Epilepsy and seizures in infancy and/or early childhood is associated with increased risk for a variety of psychiatric disorders including schizophrenia and schizophrenia-like psychoses (Bredkjaer et al. 1998; Caplan et al. 1991, 1997, 1998; Jalava and Sillanpaa 1996; Qin et al. 2005; Sachdev 1998; Schwartz and Marsh 2000; Vestergaard et al. 2005). Furthermore, psychiatric comorbidity in children with epilepsy is significantly more prevalent than in children with other chronic health conditions (Caplan et al. 2008; Jones et al. 2008; for a review see Plioplys et al. 2007). "
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    ABSTRACT: Previous work has indicated an association between seizures early in life and increased risk of psychiatric disorders, including schizophrenia. However, because early-life seizures are commonly treated with antiepileptic drugs (AEDs) such as phenobarbital, the possibility that drug treatment may affect later-life psychiatric outcomes needs to be evaluated. We therefore tested the hypothesis that phenobarbital exposure in the neonatal rat increases the risk of schizophrenia-like behavioral abnormalities in adulthood. Thus, in this study, we examined the effects of a single acute neonatal exposure to phenobarbital on adult behavioral outcomes in the rat neonatal ventral hippocampal (nVH) lesion model of schizophrenia. We compared these outcomes to those in rats a) without nVH lesions and b) with nVH lesions, without phenobarbital. The tasks used for behavioral evaluation were: amphetamine-induced locomotion, prepulse inhibition, elevated plus-maze, and novel object recognition task. We found that neonatal phenobarbital treatment (in the absence of nVH lesions) was sufficient to disrupt sensorimotor gating (as tested by prepulse inhibition) in adulthood to an extent equivalent to nVH lesions. Additionally, neonatal phenobarbital exposure enhanced the locomotor response to amphetamine in adult animals with and without nVH lesions. Our findings suggest that neonatal exposure to phenobarbital can predispose to schizophrenia-like behavioral abnormalities. Our findings underscore the importance of examining AED exposure early in life as a potential risk factor for later-life neuropsychiatric abnormalities in clinical populations.
    Neuropharmacology 02/2012; 62(7):2337-45. DOI:10.1016/j.neuropharm.2012.02.001 · 5.11 Impact Factor
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    • "This far lateral cerebral region is perhaps underexplored because homogeneous sampling of this region is poorly achieved with the typically large voxels of localized MRS or with the axial orientation of conventional MRSI arrays. We focused on inferior frontal gyrus in the present study because of prior findings in other neuroimaging modalities in this region in schizophrenia (McGuire et al., 1998; Assaf et al., 2006; Cerullo et al., 2007; Borofsky et al., 2010) and pediatric epilepsy (Caplan et al., 2008). Our unconventional sagittal-oblique MRSI prescription did access the inferior frontal gyrus and found that tNAA deficits in CPS may afflict this region as well, at least in the right hemisphere. Figure 3. MRSI findings involving NAA + NAAG (tNAA) and choline compounds (Cho) in right inferior frontal gyrus in pediatric complex partial seizure (CPS) patients and age-and gender-matched healthy controls. "
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    ABSTRACT: To investigate relationships between regional brain metabolites, social communication deficits, and seizure frequency in children and adolescents with cryptogenic epilepsy with complex partial seizures (CPS). In 12 children and adolescents with CPS and 23 age- and gender-matched healthy controls, we acquired proton magnetic resonance spectroscopic imaging (MRSI) at 1.5 T and 30 ms echo-time from bilateral inferior frontal and superior temporal gyri, regions associated with social communication deficits. Videotaped speech samples of all the subjects were coded for social communication deficits and parents provided information on seizure frequency. Four MRSI findings emerged in right inferior frontal gyrus. N-acetyl-aspartate (NAA) plus N-acetyl-aspartyl-glutamate (NAAG)--together called "tNAA"--was 11.4% lower in patients with CPS than in controls. Choline-compounds (Cho) were 15.4% lower in CPS than in controls. Within CPS, higher tNAA was associated with more frequent seizures and abnormal social communication. Localization of findings to right inferior frontal cortex supports the involvement of this area in social communication deficits and may be related to atypical lateralization of expressive language in pediatric epilepsy. Lower levels of tNAA and Cho may indicate local neuronal or glial damage or underpopulation due to excitotoxicity or other causes. The sensitivity of tNAA to seizure frequency suggests effects of ongoing CPS on neuronal and glial function in this brain region.
    Epilepsia 06/2011; 52(9):1705-14. DOI:10.1111/j.1528-1167.2011.03114.x · 4.57 Impact Factor
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