Quantitative EEG improves prediction of Sturge-Weber syndrome in infants with port-wine birthmark.

OBJECTIVE: Port-wine birthmark (PWB) is a common occurrence in the newborn, and general pediatricians, dermatologists, and ophthalmologists are often called on to make an assessment of risk for Sturge-Weber syndrome (SWS) due to workforce shortages in pediatric neurologists and MRI's low sensitivity for SWS brain involvement in infants. We therefore aimed to develop a quantitative EEG (qEEG) approach to safely screen young infants with PWB for SWS risk and optimal timing of diagnostic MRI. METHODS: Forty-eight infants (prior to first birthday) underwent EEG recording. Signal processing methods compared voltage between left and right sides using a previously defined pipeline and diagnostic threshold. In this test sample, we compared sensitivity/specificity of the qEEG metric against MRI performed after the first birthday. We also used likelihood ratio testing to determine whether qEEG adds incremental information beyond topographical extent of PWB, another risk marker of brain involvement. RESULTS: qEEG helped predict SWS risk in the first year of life (p = 0.031), with a sensitivity of 50% and a specificity of 81%. It added about 40% incremental information beyond PWB extent alone (p = 0.042). CONCLUSION: qEEG adds information to risk prediction in infants with facial PWB. SIGNIFICANCE: qEEG can be used to help determine whether to obtain an MRI in the first year of life. The data collected can assist in developing a predictive model risk calculator that incorporates both PWB extent and qEEG results, which can be validated and then employed in the community.

Altered task-related modulation of long-range connectivity in children with autism.

Functional connectivity differences between children with autism spectrum disorder (ASD) and typically developing children have been described in multiple datasets. However, few studies examine the task-related changes in connectivity in disorder-relevant behavioral paradigms. In this paper, we examined the task-related changes in functional connectivity using EEG and a movement-based paradigm that has behavioral relevance to ASD. Resting-state studies motivated our hypothesis that children with ASD would show a decreased magnitude of functional connectivity during the performance of a motor-control task. Contrary to our initial hypothesis, however, we observed that task-related modulation of functional connectivity in children with ASD was in the direction opposite to that of TDs. The task-related connectivity changes were correlated with clinical symptom scores. Our results suggest that children with ASD may have differences in cortical segregation/integration during the performance of a task, and that part of the differences in connectivity modulation may serve as a compensatory mechanism. Autism Res 2018, 11: 245-257. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Decreased connectivity between brain regions is thought to cause the symptoms of autism. Because most of our knowledge comes from data in which children are at rest, we do not know how connectivity changes directly lead to autistic behaviors, such as impaired gestures. When typically developing children produced complex movements, connectivity decreased between brain regions. In children with autism, connectivity increased. It may be that behavior-related changes in brain connectivity are more important than absolute differences in connectivity in autism.

The role of alpha oscillations in deriving and maintaining spatial relations in working memory.

Previous research has demonstrated distinct neural correlates for maintenance of abstract, relational versus concrete, sensory information in working memory (WM). Storage of spatial relations in WM results in suppression of posterior sensory regions, which suggests that sensory information is task-irrelevant when relational representations are maintained in WM. However, the neural mechanisms by which abstract representations are derived from sensory information remain unclear. Here, using electroencephalography, we investigated the role of alpha oscillations in deriving spatial relations from a sensory stimulus and maintaining them in WM. Participants encoded two locations into WM, then after an initial maintenance period, a cue indicated whether to convert the spatial information to another sensory representation or to a relational representation. Results revealed that alpha power increased over posterior electrodes when sensory information was converted to a relational representation, but not when the information was converted to another sensory representation. Further, alpha phase synchrony between posterior and frontal regions increased for relational compared to sensory trials during the maintenance period. These results demonstrate that maintaining spatial relations and locations in WM rely on distinct neural oscillatory patterns.

Decreased Modulation of EEG Oscillations in High-Functioning Autism during a Motor Control Task.

Autism spectrum disorders (ASD) are thought to result in part from altered cortical excitatory-inhibitory balance; this pathophysiology may impact the generation of oscillations on electroencephalogram (EEG). We investigated premotor-parietal cortical physiology associated with praxis, which has strong theoretical and empirical associations with ASD symptomatology. Twenty five children with high-functioning ASD (HFA) and 33 controls performed a praxis task involving the pantomiming of tool use, while EEG was recorded. We assessed task-related modulation of signal power in alpha and beta frequency bands. Compared with controls, subjects with HFA showed 27% less left central (motor/premotor) beta (18-22 Hz) event-related desynchronization (ERD; p = 0.030), as well as 24% less left parietal alpha (7-13 Hz) ERD (p = 0.046). Within the HFA group, blunting of central ERD attenuation was associated with impairments in clinical measures of praxis imitation (r = -0.4; p = 0.04) and increased autism severity (r = 0.48; p = 0.016). The modulation of central beta activity is associated, among other things, with motor imagery, which may be necessary for imitation. Impaired imitation has been associated with core features of ASD. Altered modulation of oscillatory activity may be mechanistically involved in those aspects of motor network function that relate to the core symptoms of ASD.

Practicing Novel, Praxis-Like Movements: Physiological Effects of Repetition.

Our primary goal was to develop and validate a task that could provide evidence about how humans learn praxis gestures, such as those involving the use of tools. To that end, we created a video-based task in which subjects view a model performing novel, meaningless one-handed actions with kinematics similar to praxis gestures. Subjects then imitated the movements with their right hand. Trials were repeated six times to examine practice effects. EEG was recorded during the task. As a control, subjects watched videos of a model performing a well-established (over learned) tool-use gesture. These gestures were also imitated six times. Demonstrating convergent validity, EEG measures of task-related cortical activation were similar in topography and frequency between the novel gesture task and the overlearned, praxis gesture task. As in studies assessing motor skill learning with simpler tasks, cortical activation during novel gesture learning decreased as the same gestures were repeated. In the control condition, repetition of overlearned tool-use gestures were also associated with reductions in activation, though to a lesser degree. Given that even overlearned, praxis gestures show constriction of EEG activity with repetition, it is possible that that attentional effects drive some of the repetition effects seen in EEG measures of activation during novel gesture repetition.

Dynamics of functional and effective connectivity within human cortical motor control networks.

OBJECTIVE: Praxis, the performance of complex motor gestures, is crucial to the development of motor and social/communicative capacities. Praxis relies on a network consisting of inferior parietal and premotor regions, particularly on the left, and is thought to require transformation of spatio-temporal representations (parietal) into movement sequences (premotor). METHOD: We examined praxis network dynamics by measuring EEG effective connectivity while healthy subjects performed a praxis task. RESULTS: Propagation from parietal to frontal regions was not statistically greater on the left than the right. However, propagation from left parietal regions to all other regions was significantly greater during gesture preparation than execution. Moreover, during gesture preparation only, propagation from the left parietal region to bilateral frontal regions was greater than reciprocal propagations to the left parietal region. This directional specificity was not observed for the right parietal region. CONCLUSIONS: These findings represent direct electrophysiological evidence for directionally predominant propagation in left frontal-parietal networks during praxis behavior, which may reflect neural mechanisms by which representations in the human brain select appropriate motor sequences for subsequent execution. SIGNIFICANCE: In addition to bolstering the classic view of praxis network function, these results also demonstrate the relevance of additional information provided by directed connectivity measures.

Maintenance of relational information in working memory leads to suppression of the sensory cortex.

Working memory (WM) for sensory-based information about individual objects and their locations appears to involve interactions between lateral prefrontal and sensory cortexes. The mechanisms and representations for maintenance of more abstract, nonsensory information in WM are unknown, particularly whether such actively maintained information can become independent of the sensory information from which it was derived. Previous studies of WM for individual visual items found increased electroencephalogram (EEG) alpha (8-13 Hz) power over posterior electrode sites, which appears to correspond to the suppression of cortical areas that represent irrelevant sensory information. Here, we recorded EEG while participants performed a visual WM task that involved maintaining either concrete spatial coordinates or abstract relational information. Maintenance of relational information resulted in higher alpha power in posterior electrodes. Furthermore, lateralization of alpha power due to a covert shift of attention to one visual hemifield was marginally weaker during storage of relational information than during storage of concrete information. These results suggest that abstract relational information is maintained in WM differently from concrete, sensory representations and that during maintenance of abstract information, posterior sensory regions become task irrelevant and are thus suppressed.

Inhibition drives early feature-based attention.

Attention can modulate processing of visual input according to task-relevant features, even as early as approximately 100 ms after stimulus presentation. In the present study, event-related potential and behavioral data revealed that inhibition of distractor features, rather than activation of target features, is the primary driver of early feature-based selection in human observers. This discovery of inhibition consistent with task goals during early visual processing suggests that inhibition plays a much larger role at an earlier stage of target selection than previously recognized. It also highlights the importance of understanding the role of inhibition (in addition to activation) in attention.

Multiple task interference is greater in children with ADHD.

There is considerable lay discussion that children with attention deficit hyperactivity disorder (ADHD) have increased difficulty with multitasking, but there are few experimental data. In the current study, we examine the simultaneous processing of two stimulus-response tasks using the Psychological Refractory Period (PRP) effect. We hypothesized that children with ADHD would show a greater PRP effect, suggesting a prolonged "bottleneck" in stimulus-response processing. A total of 19 school-aged children with ADHD showed a prolonged PRP effect compared with 25 control children, suggesting a higher cognitive cost in ADHD for multitasking.

Use of quantitative EEG in infants with port-wine birthmark to assess for Sturge-Weber brain involvement.

OBJECTIVE: Many infants born with a facial port-wine (PW) birthmark will not develop brain involvement of Sturge-Weber syndrome (SWS). Previous studies have shown asymmetry in quantitative EEG (qEEG) correlates with degree of clinical impairment in children and adults with known SWS. We hope to determine if quantitative qEEG can be used as a method to predict which infants are most likely to develop SWS brain involvement on MRI. The current study looks at the ability of qEEG to differentiate between infants with radiographically demonstrated SWS and those without. METHODS: We first performed an observational study of qEEG results on eight infants with facial PW birthmark (four had SWS brain involvement). We recorded standard clinical EEGs and then derived a measure of asymmetry. We subsequently validated this threshold through a study of an additional nine infants with PW birthmark (five with SWS brain involvement). RESULTS: Quantitative EEG correctly identified infants with SWS brain involvement in all cases in the Validation cohort. This technique was at least as good as a pediatric electroencephalographer with extensive experience reading SWS EEGs. CONCLUSIONS: This study demonstrates the ability for qEEG to discriminate between those infants with SWS brain involvement and those with neurologically asymptomatic PW birthmark. SIGNIFICANCE: This study represents an important step toward the development of a qEEG technique able to predict which infants with PW birthmark will develop SWS brain involvement.

Functional magnetic resonance imaging reveals neuroanatomical dissociations during semantic integration in schizophrenia.

BACKGROUND: Schizophrenia symptoms can be conceptualized in terms of a breakdown of a balance between 1) activating, retrieving, and matching stored representations to incoming information (semantic memory-based processing) and 2) fully integrating activated semantic representations with one another and with other types of representations to form a gestalt representation of meaning (semantic integration). Semantic memory-based processes are relatively more dependent on inferior frontal and temporal cortices, whereas particularly demanding integrative processes additionally recruit the dorsolateral prefrontal cortex (DLPFC) and sometimes parietal cortices. We used functional magnetic resonance imaging (fMRI) to determine whether the modulation of temporal/inferior frontal cortices and the DLPFC can be neuroanatomically dissociated in schizophrenia, as semantic integration demands increase. Integration demands were manipulated by varying the nature (concrete vs. abstract) and the congruity (incongruous vs. congruous) of words within sentences. METHODS: Sixteen right-handed schizophrenia patients and 16 healthy volunteers, matched on age and parental socioeconomic status, underwent event-related fMRI scanning while they read sentences. Blood oxygen level dependent (BOLD) effects were contrasted to words within sentences that were 1) concrete versus abstract and 2) semantically incongruous versus congruous with their preceding contexts. RESULTS: In both contrasts, large networks mediating the activation and retrieval of verbal and imagistic representations were normally modulated in patients. However, unlike control subjects, patients failed to recruit the DLPFC, medial frontal and parietal cortices to incongruous (relative to congruous) sentences, and failed to recruit the DLPFC to concrete (relative to abstract) sentences. CONCLUSIONS: As meaning is built from language, schizophrenia patients demonstrate a neuroanatomical dissociation in the modulation of temporal/inferior frontal cortices and the DLPFC.

Neuroanatomical distinctions within the semantic system during sentence comprehension: evidence from functional magnetic resonance imaging.

To make sense of a sentence, we must compute morphosyntactic and semantic-thematic relationships between its verbs and arguments and evaluate the resulting propositional meaning against any preceding context and our real-world knowledge. Recent electrophysiological studies suggest that, in comparison with non-violated verbs (e.g. "...at breakfast the boys would eat..."), animacy semantic-thematically violated verbs (e.g. "...at breakfast the eggs would eat...") and morphosyntactically violated verbs (e.g. "...at breakfast the boys would eats...") evoke a similar neural response. This response is distinct from that evoked by verbs that only violate real-world knowledge (e.g. "...at breakfast the boys would plant..."). Here we used fMRI to examine the neuroanatomical regions engaged in response to these three violations. Real-world violations, relative to other sentence types, led to increased activity within the left anterior inferior frontal cortex, reflecting participants' increased and prolonged efforts to retrieve semantic knowledge about the likelihood of events occurring in the real world. In contrast, animacy semantic-thematic violations of the actions depicted by the central verbs engaged a frontal/inferior parietal/basal ganglia network known to mediate the execution and comprehension of goal-directed action. We suggest that the recruitment of this network reflected a semantic-thematic combinatorial process that involved an attempt to determine whether the actions described by the verbs could be executed by their NP Agents. Intriguingly, this network was also activated to morphosyntactic violations between the verbs and their subject NP arguments. Our findings support the pattern of electrophysiological findings in suggesting (a) that a clear division within the semantic system plays out during sentence comprehension, and (b) that semantic-thematic and syntactic violations of verbs within simple active sentences are treated similarly by the brain.

Task and semantic relationship influence both the polarity and localization of hemodynamic modulation during lexico-semantic processing.

This study examined how task (implicit vs. explicit) and semantic relationship (direct vs. indirect) modulated hemodynamic activity during lexico-semantic processing. Participants viewed directly related, indirectly related, and unrelated prime-target word-pairs as they performed (a) an implicit lexical decision (LD) task in which they decided whether each target was a real word or a nonword, and (b) an explicit relatedness judgment (RJ) task in which they determined whether each word-pair was related or unrelated in meaning. Task influenced both the polarity and neuroanatomical localization of hemodynamic modulation. Semantic relationship influenced the neuroanatomical localization of hemodynamic modulation. The implicit LD task was primarily associated with inferior prefrontal and ventral inferior temporal/fusiform hemodynamic response suppression to directly related (relative to unrelated) word-pairs, and with more widespread temporal-occipital response suppression to indirectly related (relative to unrelated) word-pairs. In contrast, the explicit RJ task was primarily associated with left inferior parietal hemodynamic response enhancement to both directly and indirectly related (relative to unrelated) word-pairs, as well as with additional left inferior prefrontal hemodynamic response enhancement to indirectly related (relative to unrelated) word-pairs. These findings are discussed in relation to the specific neurocognitive processes thought to underlie implicit and explicit semantic processes. Hum Brain Mapp, 2008. (c) 2007 Wiley-Liss, Inc.

Making sense of discourse: an fMRI study of causal inferencing across sentences.

To build up coherence between sentences (comprehend discourse), we must draw inferences, i.e. activate and integrate information that is not actually stated. We used event-related fMRI to determine the localization and extent of brain activity mediating causal inferencing across short, three-sentence scenarios. Participants read and made causal coherence judgments to sentences that were highly causally related, intermediately related or unrelated to their preceding two-sentence contexts. The highly related and intermediately related scenarios were matched in terms of semantic similarities between their individual component words. A pre-rating study established that causal inferences were generated to the intermediately related but not to the highly related or unrelated scenarios. In the scanner, sentences that were intermediately related (relative to highly related or unrelated) to their preceding contexts were associated with longer judgment reaction times and sustained increases in hemodynamic activity within left lateral temporal/inferior parietal/prefrontal cortices, the right inferior prefrontal gyrus and bilateral superior medial prefrontal cortices. In contrast, sentences that were unrelated (relative to highly related) to their preceding contexts were associated with only transient increases in activity (at, but not after, the peak of the hemodynamic response) within the right lateral temporal cortex and the right inferior prefrontal gyrus. These data suggest that, to make sense of discourse, we activate a large bilateral cortical network in response to what is not explicitly stated. We suggest that this network reflects the activation, retrieval and integration of information from long-term semantic memory into incoming discourse structure during causal inferencing.