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ABSTRACT: PURPOSE: To elucidate differences in the disruption of language network function, as measured by blood oxygenation level-dependent (BOLD) contrast functional MRI (fMRI), attributable to two common sedative agents administered to infants under clinical imaging protocols. MATERIALS AND METHODS: The sedatives pentobarbital (Nembutal) and Propofol, administered clinically to infants at 1 year of age, were compared with respect to BOLD activation profiles in response to passive story-listening stimulation. An intermittent event-related imaging protocol was used with which the temporal evolution of language processing resulting from this stimulation was explored. RESULTS: Propofol and Nembutal were found to have distinct and complementary responses to story-listening. Propofol exhibited more activation in higher processing networks with increasing response toward the end of narrative stimulus. Nembutal, in contrast, had much more robust activation of primary and secondary sensory cortices but a decreasing response over time in fronto-parietal default-mode regions. This may suggest a breakdown of top-down feedback for Propofol versus the lack of bottom-up feed-forward processing for Nembutal. CONCLUSION: Two popular sedative agents for use in children for clinical fMRI were found to induce distinct alteration of activation patterns from a language stimulus. This has ramifications for clinical fMRI of sedated infants and encourages further study to build a framework for more confident interpretation. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.
Journal of Magnetic Resonance Imaging 03/2013; · 2.70 Impact Factor
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ABSTRACT: Semantic association, an essential element of human language, enables discourse and inference. Neuroimaging studies have revealed localization and lateralization of semantic circuitry, making substantial contributions to cognitive neuroscience. However, because of methodological limitations, these investigations have only identified individual functional components rather than capturing the behavior of the entire network. To overcome these limitations, we have implemented group independent component analysis (ICA) to investigate the cognitive modules used by healthy adults performing the fMRI semantic decision task. When compared with the results of a standard general linear modeling (GLM) analysis, ICA detected several additional brain regions subserving semantic decision. Eight task-related group ICA maps were identified, including left inferior frontal gyrus (BA44/45), middle posterior temporal gyrus (BA39/22), angular gyrus/inferior parietal lobule (BA39/40), posterior cingulate (BA30), bilateral lingual gyrus (BA18/23), inferior frontal gyrus (L>R, BA47), hippocampus with parahippocampal gyrus (L>R, BA35/36), and anterior cingulate (BA32/24). Although most of the components were represented bilaterally, we found a single, highly left-lateralized component that included the inferior frontal gyrus and the medial and superior temporal gyri, the angular and supramarginal gyri, and the inferior parietal cortex. The presence of these spatially independent ICA components implies functional connectivity and can be equated with their modularity. These results are analyzed and presented in the framework of a biologically plausible theoretical model in preparation for similar analyses in patients with right- or left-hemispheric epilepsies.
Epilepsy & Behavior 02/2011; 20(4):613-22. · 2.34 Impact Factor
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ABSTRACT: Chronic and progressive brain injury, as seen in epilepsy, may alter brain networks that underlie cognitive functions. To evaluate the effect of epilepsy on language functions we investigated the neuroanatomical basis of semantic processing in patients with left (LHE) or right (RHE) hemispheric onset epilepsy using semantic decision fMRI paradigm and group independent component analysis (ICA); we then compared the results of our investigations with language networks in healthy subjects examined with the same language task (Kim K, Karunanayaka P, Privitera M, Holland S, Szaflarski J. Semantic association investigated with fMRI and independent component analysis. In press). Group ICA is a data-driven technique capable of revealing the functional organization of the human brain based on fMRI data. In addition to providing functional connectivity information, ICA can also provide information about the temporal dynamics of underlying networks subserving specific cognitive functions. In this study, we implemented two complementary analyses to investigate group differences in underlying network dynamics based on associated independent component (IC) time courses (a priori defined criterion or a posteriori identified maximum likelihood descriptor). We detected several differences between healthy controls and patients with epilepsy not previously observed with standard fMRI analysis methods. Our analyses confirmed the presence of different effects of LHE or RHE on the behavior of the language network. In particular, a major difference was noted in the nodes subserving verbal encoding and retrieval in the bilateral medial temporal regions. These effects were dependent on the side of the epilepsy onset; that is, effects were different with left or right hemispheric epilepsy. These findings may explain the differences in verbal and nonverbal memory abilities between patients with left and those with right hemispheric epilepsy. Further, although the effects on other nodes of the network were more subtle, several deviations from normal network function were observed in patients with LHE (e.g., alterations in the functions of the primarily left frontotemporal network module) or in patients with RHE (e.g., differences in the medial retrosplenial module responsible for mental imagery or in the anterior cingulate module subserving attention control). These findings not only highlight the negative effects of epilepsy on the main left hemispheric language network nodes in patients with LHE, but also document the effects of epilepsy on other language network nodes whether exerted by LHE or RHE. Further, these results document the advantages of using group ICA for investigating the effects of disease state (e.g., epilepsy) on the network subserving cognitive processing and provide an interesting avenue for further exploration.
Epilepsy & Behavior 01/2011; 20(4):623-32. · 2.34 Impact Factor
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ABSTRACT: Human language is a complex and protean cognitive ability. Young children, following well defined developmental patterns learn language rapidly and effortlessly producing full sentences by the age of 3 years. However, the language circuitry continues to undergo significant neuroplastic changes extending well into teenage years. Evidence suggests that the developing brain adheres to two rudimentary principles of functional organization: functional integration and functional specialization. At a neurobiological level, this distinction can be identified with progressive specialization or focalization reflecting consolidation and synaptic reinforcement of a network (Lenneberg, 1967; Muller et al., 1998; Berl et al., 2006). In this paper, we used group independent component analysis and linear structural equation modeling (McIntosh and Gonzalez-Lima, 1994; Karunanayaka et al., 2007) to tease out the developmental trajectories of the language circuitry based on fMRI data from 336 children ages 5-18 years performing a blocked, covert verb generation task. The results are analyzed and presented in the framework of theoretical models for neurocognitive brain development. This study highlights the advantages of combining both modular and connectionist approaches to cognitive functions; from a methodological perspective, it demonstrates the feasibility of combining data-driven and hypothesis driven techniques to investigate the developmental shifts in the semantic network.
Frontiers in Systems Neuroscience 01/2011; 5:29.
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ABSTRACT: Narrative comprehension is a fundamental cognitive skill that involves the coordination of different functional brain regions. We develop a spectral graphical model with model averaging to study the connectivity networks underlying these brain regions using fMRI data collected from a story comprehension task. Based on the spectral density matrices in the frequency domain, this model captures the temporal dependency of the entire fMRI time series between brain regions. A Bayesian model averaging procedure is then applied to select the best directional links that constitute the brain network. Using this model, brain networks of three distinct age groups are constructed to assess the dynamic change of network connectivity with respect to age.
Brain connectivity. 01/2011; 1(5):389-400.
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ABSTRACT: Semantic language skills are an integral part of early childhood language development. The semantic association between verbs and nouns constitutes an important building block for the construction of sentences. In this large-scale functional magnetic resonance imaging (fMRI) study, involving 336 subjects between the ages of 5 and 18 years, we investigated the neural correlates of covert verb generation in children. Using group independent component analysis (ICA), seven task-related components were identified including the mid-superior temporal gyrus, the most posterior aspect of the superior temporal gyrus, the parahippocampal gyrus, the inferior frontal gyrus, the angular gyrus, and medial aspect of the parietal lobule (precuneus/posterior cingulate). A highly left-lateralized component was found including the medial temporal gyrus, the frontal gyrus, the inferior frontal gyrus, and the angular gyrus. The associated independent component (IC) time courses were analyzed to investigate developmental changes in the neural elements supporting covert verb generation. Observed age effects may either reflect specific local neuroplastic changes in the neural substrates supporting language or a more global transformation of neuroplasticity in the developing brain. The results are analyzed and presented in the framework of two theoretical models for neurocognitive brain development. In this context, group ICA of fMRI data from our large sample of children aged 5-18 years provides strong evidence in support of the regionally weighted model for cognitive neurodevelopment of language networks.
NeuroImage 05/2010; 51(1):472-87. · 5.89 Impact Factor
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ABSTRACT: Attentional deficits are common and significant sequelae of pediatric traumatic brain injury (TBI). However, little is known about how the underlying neural processes that support different components of attention are affected. The present study examined brain activation patterns using fMRI in a group of young children who sustained a TBI in early childhood (n = 5; mean age = 9.4), and a group of age-matched control children with orthopedic injuries (OI) (n = 8) during a continuous performance task (CPT). Four children in the TBI group had moderate injuries, and one had a severe injury. Performance on the CPT task did not differ between groups. Both TBI and OI children activated similar networks of brain regions relevant to sustained attention processing, but the TBI group demonstrated several areas of significantly greater activation relative to controls, including frontal and parietal regions. These findings of over-activation of the relevant attention network in the TBI group contrast with those obtained in imaging studies of Attention-Deficit/Hyperactivity Disorder where under-activation of the attention network has been documented. This study provides evidence that young children's brains function differently following a traumatic brain injury, and that these differences persist for years after the injury.
Journal of the International Neuropsychological Society 06/2008; 14(3):424-35. · 2.76 Impact Factor
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ABSTRACT: Structural Equation Modeling (SEM) or path analysis is a multivariate analytic tool that is used to test hypothesis about causal influences among measured or latent variables. When applied to functional neuroimaging (fMRI) data, SEM combines interregional covariance and neuroanatomy to investigate brain connectivity and the dynamic flow of information across neural networks. We have investigate Linear SEM or LSEM as a first step in estimating connection strengths from fMRI data in children during acoustic stimulation with stories in English. An average LSEM was constructed based on the concatenated fMRI data from N=313 children, age 5 to 18, listening to stories. Time courses from the fMRI data is used as input to the LSEM as computed in AMOS (v.5.1, SmallWaters, Corp. Chicago, IL) to yield an average model for the entire group. The LSEM path coefficients were examined between brain regions involved in auditory speech perception and language processing. Connectivities estimated by LSEM are significantly age dependent in some brain areas, while the connectivity coefficient between other brain regions is not a function of age.
The Journal of the Acoustical Society of America 06/2008; 123(5):3425. · 1.55 Impact Factor
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ABSTRACT: Functional MRI (fMRI) performed in infants with congenital hearing loss provides evidence that auditory language stimulation produces activation of the central auditory system in the brain. Babies are normally sedated for clinical MRI scans. With IRB approval we have added a 10 minute fMRI scanning procedure to clinically indicated MRI scans in infants with severe to profound hearing impairment (n=18) or normal hearing (n=22). Sedation is performed according to clinical guidelines at our institution using either Propofol ((200-250 mcgkgmin i.v.) or pentobarbital (5 mgkg orally). fMRI scanning is performed using Echo-planar gradient echo acquisitions on a 3 Tesla clinical MRI system while a mothers voice reads stories to the babies at a sound level 10 dB above the measured hearing threshold. Brain activation is measured in primary auditory cortex and planum temporale speech recognition areas. Results in the normal hearing group of infants demonstrates that the central auditory system is stimulated by speech in infants, although sedation does attenuate brain activation in a dose dependent manner. Central auditory and language activation is also detected in hearing impaired infants with levels of activation correlating to measured hearing thresholds.
The Journal of the Acoustical Society of America 06/2008; 123(5):3319. · 1.55 Impact Factor
