Cortical morphology, epileptiform discharges, and neuropsychological performance in BECTS.
ABSTRACT: OBJECTIVES:The aim of this study was to understand the relationship between cortical morphology, centrotemporal spike (CTS), and neuropsychological functioning in children with BECTS compared to their typically developing peers. MATERIALS AND METHODS:To examine whole-brain differences in cortical thickness between groups, a general linear model approach was applied to T1-weighted structural magnetic resonance imaging (MRI) in children with BECTS and typically developing children. Further region-of-interest (ROI) analyses were performed to examine the effects of frequency and lateralization of CTS. In addition, the relationship between Processing Speed Index (PSI) and cortical thickness was investigated. RESULTS:Twenty-three patients with BECTS and thirty-two controls were included. There was no statistically significant difference in global cortical thickness between groups. With ROI analyses, we found significantly thinner cortex within right pars opercularis when comparing children with right predominant CTS, and with very frequent right CTS (>10/min) to the control group (P = 0.028 and P = 0.026, respectively). A statistically significant interaction of group (controls vs BECTS) and PSI was seen in bilateral frontal and right superior parietal cortices, indicating a positive relationship between cortical thickness and PSI in healthy controls but not BECTS. CONCLUSION:A region of cortex where right CTS may originate was thinner in BECTS compared to children without BECTS. Typically developing children with faster processing speed had thicker cortices in regions supporting visuomotor integration, motor, and executive function, but this relationship was not observed in BECTS. These results suggest that BECTS is associated with atypical cortical morphology that may underlie poorer neuropsychological performance.
Project description:Benign epilepsy with centrotemporal spikes (BECTS), the most common focal childhood epilepsy, is associated with subtle abnormalities in cognition and possible developmental alterations in brain structure when compared to healthy participants, as indicated by previous cross-sectional studies. To examine the natural history of BECTS, we investigated cognition, cortical thickness, and subcortical volumes in children with new/recent onset BECTS and healthy controls (HC).Participants were 8-15 years of age, including 24 children with new-onset BECTS and 41 age- and gender-matched HC. At baseline and 2 years later, all participants completed a cognitive assessment, and a subset (13 BECTS, 24 HC) underwent T1 volumetric magnetic resonance imaging (MRI) scans focusing on cortical thickness and subcortical volumes.Baseline cognitive abnormalities associated with BECTS (object naming, verbal learning, arithmetic computation, and psychomotor speed/dexterity) persisted over 2 years, with the rate of cognitive development paralleling that of HC. Baseline neuroimaging revealed thinner cortex in BECTS compared to controls in frontal, temporal, and occipital regions. Longitudinally, HC showed widespread cortical thinning in both hemispheres, whereas BECTS participants showed sparse regions of both cortical thinning and thickening. Analyses of subcortical volumes showed larger left and right putamens persisting over 2 years in BECTS compared to HC.Cognitive and structural brain abnormalities associated with BECTS are present at onset and persist (cognition) and/or evolve (brain structure) over time. Atypical maturation of cortical thickness antecedent to BECTS onset results in early identified abnormalities that continue to develop abnormally over time. However, compared to anatomic development, cognition appears more resistant to further change over time.
Project description:BECTS (benign epilepsy with centro-temporal spikes) is one of the most common childhood-onset epilepsy syndromes. We investigated quantitative evidence for brain morphological variation associated with BECTS to provide insights into the neuroanatomical basis of this disorder.Three independent BECTS groups were imaged at different stages: (a) near onset (n=16, mean age 9.3±1.6 years), (b) ~9 years after onset (n=9, mean age 15.8±2.3 years), and (c) ~15 years after onset (n=10, mean age 22.7±2.7 years). Age-matched controls were imaged with each group. Whole brain T1-weighted MRI was acquired. Voxel-based morphometry (groups a-c) and cortical thickness analyses (groups b and c) were undertaken within each group and for the groups combined. The relationship between cortical morphology and age was investigated.The voxel-based morphometry analysis indicated increased bilateral grey matter volume in the superior frontal gyrus, insula and right inferior frontal gyrus regions in BECTS. The magnitude of the increase lessened with age of the cases. Cortical thickness analysis revealed thicker cortex in BECTS along middle and inferior frontal gyri bilaterally, left insula and bilateral supramarginal gyrus in the 9-year-after-onset group, that normalised with age. The rate of cortical thickness changes with age were greater in BECTS cases than in controls.Increased cortical gray matter associated with BECTS was found. The decreasing magnitude of the effect with increasing age parallels the natural history of the disorder. The areas affected are consistent with neurocognitive dysfunction in BECTS.
Project description:The ventromedial prefrontal cortex (VMPFC) is a key center of affect regulation and processing, fundamental aspects of emotional competence which are disrupted in mood disorders. Structural alterations of VMPFC have consistently been observed in adult major depression and are associated with depression severity, yet it is unknown whether young children with depression demonstrate similar abnormalities. We investigated cortical thickness differences in the VMPFC of children with a history of preschool-onset depression (PO-MDD).Participants in a longitudinal study of PO-MDD underwent structural brain imaging between the ages of 7 and 12 years. Using local cortical distance metrics, cortical thickness of the VMPFC was compared in children with and without a history of PO-MDD.Children previously diagnosed with PO-MDD (n=34) had significantly thinner right VMPFC vs. children without a history of PO-MDD [(n=95); F(1,126)=5.97, (p=.016)]. This effect was specific to children with a history of PO-MDD vs. other psychiatric conditions and was independent of comorbid anxiety or externalizing disorders. Decreases in right VMPFC thickness were predicted by preschool depressive symptoms independent of depressive symptoms in school age.Results are cross-sectional and cannot distinguish whether thinner right VMPFC represents a vulnerability marker of MDD, consequence of MDD, or marker of remitted MDD. Longitudinal imaging is needed to contextualize how this difference relates to normative VMPFC structural development.Onset of depression at preschool age was associated with decreased cortical thickness of right VMPFC. This finding implicates the VMPFC in depression from very early stages of brain development.
Project description:Children born extremely preterm (<?28 weeks gestation, EPT) are at increased risk for language and other neurocognitive deficits compared to term controls (TC). Prior studies have reported both increases and decreases in cortical thickness in EPT across the cerebrum. These studies have not formally normalized for intracranial volume (ICV), which is especially important as EPT children often have smaller stature, head size, and ICV. We previously reported increased interhemispheric functional and structural connectivity in a well-controlled group of school-aged EPT children with no known brain injury or neurological deficits. Functional and structural hyperconnectivity between left and right temporoparietal regions was positively related with language scores in EPT, which may be reflected in measures of cortical thickness. To characterize possible language network cortical thickness effects, 15 EPT children and 15 TC underwent standardized assessments of language and structural magnetic resonance imaging at 4 to 6 years of age. Images were subjected to volumetric and cortical thickness analyses using FreeSurfer. Whole-brain analyses of cortical thickness were conducted both with and without normalization by ICV. Non-normalized results showed thinner temporal cortex for EPT, while ICV-normalized results showed thicker cortical regions in the right temporal lobe (FDRq?=?0.05). Only ICV-normalized results were significantly related to language scores, with right temporal cortical thickness being positively correlated with performance.
Project description:Tau pathology has been associated with neuronal loss at autopsy, but the temporal evolution of tau pathology and atrophy remains unclear. Here, we investigate the association between cross-sectional AV-1451-PET as a marker of tau pathology and cortical thickness cross-sectionally. We also investigated retrospective rates of cortical thinning over the three years preceding the AV-1451 scan in a clinically normal cohort of 103 older adults from the Harvard Aging Brain Study. Tau measurements were Geometric Transfer Matrix partial volume corrected standardized uptake value ratios (SUVRs) with a cerebellar gray reference region. Thirty-four FreeSurfer-defined cortical regions of interest (ROIs) were used for both thickness and AV-1451 in each hemisphere, with seven additional volumetric ROIs. We examined "local" relationships between AV-1451 and cortical thickness in the same ROI, as well as inferior temporal AV-1451 and all thickness ROIs. All models included baseline age and sex, both interacting with time in retrospective longitudinal models, as covariates. Cross-sectional models controlled for the number of days between the two scans. Cross-sectional local comparisons revealed significant associations between elevated AV-1451 and thinner cortical ROIs predominantly in temporal regions, while analyses associating inferior temporal AV-1451 with all cortical ROIs showed a widespread pattern of significant relationships, which was strongest in temporal and parietal cortices. In our retrospective longitudinal analyses, we saw significant relationships in temporal and parietal regions. Significant local relationships were seen in right superior temporal, middle temporal, temporal pole, and fusiform, as well as the left cuneus and banks of the left superior temporal sulcus. Significant relationships between inferior temporal AV-1451 and faster thinning were observed in right temporal regions (middle temporal and fusiform) and bilateral parahippocampal cortices. We observed significant negative relationships between local and inferior temporal AV-1451 signal and both cross-sectional cortical thickness and rates of thinning in lateral and medial temporal regions. This is an important early step toward elucidating the relationship between tau pathology and retrospective longitudinal atrophy in aging and preclinical AD.
Project description:Long-term remitted Cushing's disease (LTRCD) patients commonly continue to present persistent psychological and cognitive deficits, and alterations in brain function and structure. Although previous studies have conducted gray matter volume analyses, assessing cortical thickness and surface area of LTRCD patients may offer further insight into the neuroanatomical substrates of Cushing's disease. Structural 3T magnetic resonance images were obtained from 25 LTRCD patients, and 25 age-, gender-, and education-matched healthy controls (HCs). T1-weighted images were segmented using FreeSurfer software to extract mean cortical thickness and surface area values of 68 cortical gray matter regions and two whole hemispheres. Paired sample t tests explored differences between the anterior cingulate cortex (ACC; region of interest), and the whole brain. Validated scales assessed psychiatric symptomatology, self-reported cognitive functioning, and disease severity. After correction for multiple comparisons, ROI analyses indicated that LTRCD-patients showed reduced cortical thickness of the left caudal ACC and the right rostral ACC compared to HCs. Whole-brain analyses indicated thinner cortices of the left caudal ACC, left cuneus, left posterior cingulate cortex, right rostral ACC, and bilateral precuneus compared to HCs. No cortical surface area differences were identified. Cortical thickness of the left caudal ACC and left cuneus were inversely associated with anxiety symptoms, depressive symptoms, and disease duration, although certain associations did not persist after correction for multiple testing. In six of 68 regions examined, LTRCD patients had reduced cortical thickness in comparison to HCs. Cortical thickness of the left caudal ACC was inversely associated with disease duration. This suggests that prolonged and excessive exposure to glucocorticoids may be related to cortical thinning of brain structures involved in emotional and cognitive processing.
Project description:Few studies have focused on the neuroanatomy of aggressive behavior in children younger than 10 years. Here, we explored the neuroanatomical correlates of aggression in a population-based sample of 6- to 9-year-old children using a multiple-informant approach.Magnetic resonance (MR) scans were acquired from 566 children from the Generation R study who participated in the Berkeley Puppet Interview and whose parents had completed the Child Behavior Checklist. Linear regression analyses were used to examine associations between aggression and amygdala and hippocampal volume. We performed surface-based analyses to study the association between aggression and cortical thickness, surface area, and gyrification.Aggressive behavior was associated with smaller amygdala (p < .05) but not hippocampal volume. Aggression was associated with a thinner cortex in the left precentral cortex (p < .01) and in a cluster including the right inferior parietal, supramarginal, and postcentral cortex (p < .001). Gender moderated the association between aggression and cortical thickness in the right medial posterior cortex (p = .001) and the right prefrontal cortex (p < .001). Aggression was associated with decreased gyrification in a large cluster including the right precentral, postcentral, frontal, and parietal cortex (p = .01). Moreover, aggression was associated with decreased gyrification in the right occipital and parietal cortex (p = .02).We found novel evidence that childhood aggressive behavior is related to decreased amygdala volume, decreased sensorimotor cortical thickness, and decreased global right hemisphere gyrification. Aggression is related to cortical thickness in regions associated with the default mode network, with negative associations in boys and positive associations in girls.
Project description:Developmental dyslexia is frequently associated with atypical brain structure and function within regions of the left hemisphere reading network. To date, few studies have employed surface-based techniques to evaluate cortical thickness and local gyrification in dyslexia. Of the existing cortical thickness studies in children, many are limited by small sample size, variability in dyslexia identification, and the recruitment of prereaders who may or may not develop reading impairment. Further, no known study has assessed local gyrification index (LGI) in dyslexia, which may serve as a sensitive indicator of atypical neurodevelopment. In this study, children with dyslexia (n = 31) and typically decoding peers (n = 45) underwent structural magnetic resonance imaging to assess whole-brain vertex-wise cortical thickness and LGI. Children with dyslexia demonstrated reduced cortical thickness compared with controls within previously identified reading areas including bilateral occipitotemporal and occipitoparietal regions. Compared with controls, children with dyslexia also showed increased gyrification in left occipitotemporal and right superior frontal cortices. The convergence of thinner and more gyrified cortex within the left occipitotemporal region among children with dyslexia may reflect its early temporal role in processing word forms, and highlights the importance of the ventral stream for successful word reading.
Project description:Benign epilepsy with centrotemporal spikes (BECTS) is the most common idiopathic childhood epilepsy, which is often associated with developmental disorders in children. In the present study, we analyzed resting state EEG spectral changes in the sensor and source spaces in eight BECTS patients compared with nine age-matched controls. Using high-resolution scalp EEG data, we assessed statistical differences in spatial distributions of EEG power spectra and cortical sources of resting state EEG rhythms in five frequency bands: ? (0.5-3.5 Hz), ? (4-8 Hz), ? (8.5-13 Hz), ?1 (13.5-20 Hz) and ?2 (20.5-30 Hz) under the eyes-closed resting state condition. To further investigate the impact of centrotemporal spikes on EEG spectra, we split the EEG data of the patient group into EEG portions with and without spikes. Source localization demonstrated the homogeneity of our population of BECTS patients with a common epileptic zone over the right centrotemporal region. Significant differences in terms of both spectral power and cortical source densities were observed between controls and patients. Patients were characterized by significantly increased relative power in ?, ?, ?1 and ?2 bands in the right centrotemporal areas over the spike zone and in the right temporo-parieto-occipital junction. Furthermore, the relative power in all bands significantly decreased in the bilateral frontal and parieto-occipital areas of patients regardless of the presence or absence of spikes in EEG segments. However, the spectral differences between patients and controls were more pronounced in the presence of spikes. This observation emphasized the impact of benign epilepsy on cortical source power, especially in the right centrotemporal regions. Spectral changes in bilateral frontal and parieto-occipital areas may also suggest alterations in the default mode network in BECTS patients.
Project description:OBJECTIVE:Children with attention-deficit/hyperactivity disorder (ADHD) have delayed cortical maturation, evidenced by regionally specific slower cortical thinning. However, the relationship between cortical maturation and attention capacities in typically developing children is unknown. This study examines cortical thickness correlates of inattention symptoms in a large sample of healthy children. METHOD:Data from 357 healthy subjects (6.0-18.4 years of age) were obtained from the NIH MRI Study of Normal Brain Development. In cross-sectional analysis (first visit, n = 257), Child Behavior Checklist Attention Problems (AP) scores were linearly regressed against cortical thickness, controlling for age, gender, total brain volume, and site. For longitudinal data (up to three visits, n = 357/672 scans), similar analyses were performed using mixed-effects linear regressions. Interactions of AP with age and gender were tested. RESULTS:A cross-sectional "AP by age" interaction was found in bilateral orbito-frontal cortex, right inferior frontal cortex, bilateral ventromedial prefrontal cortex, bilateral dorsolateral prefrontal cortex, and several additional attention network regions. The interaction was due to negative associations between AP and thickness in younger subjects (6-10 years of age) that gradually disappeared over time secondary to slower cortical thinning. Similar trends were present in longitudinal analyses. CONCLUSIONS:Higher AP scores were associated with thinner cortex at baseline and slower cortical thinning with aging in multiple areas involved in attention processes. Similar patterns have been identified in ADHD, suggesting a dimensional component to the link between attention and cortical maturation. The identified association between cortical maturation and attention in healthy development will help to inform studies of neuroimaging biomarkers of ADHD.