Alexander Moiseev

Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age

Summary Neonatal pain‐related stress is associated with altered brain activity and visual‐perceptual abilities in school‐age children born at extremely low gestational age. Abstract Children born very prematurely (≤32 weeks) often exhibit visual‐perceptual difficulties at school‐age, even in the absence of major neurological impairment. The alterations in functional brain activity that give rise to such problems, as well as the relationship between adverse neonatal experience and neurodevelopment, remain poorly understood. Repeated procedural pain‐related stress during neonatal intensive care has been proposed to contribute to altered neurocognitive development in these children. Due to critical periods in the development of thalamocortical systems, the immature brain of infants born at extremely low gestational age (ELGA; ≤28 weeks) may have heightened vulnerability to neonatal pain. In a cohort of school‐age children followed since birth we assessed relations between functional brain activity measured using magnetoencephalogragy (MEG), visual‐perceptual abilities and cumulative neonatal pain. We demonstrated alterations in the spectral structure of spontaneous cortical oscillatory activity in ELGA children at school‐age. Cumulative neonatal pain‐related stress was associated with changes in background cortical rhythmicity in these children, and these alterations in spontaneous brain oscillations were negatively correlated with visual‐perceptual abilities at school‐age, and were not driven by potentially confounding neonatal variables. These findings provide the first evidence linking neonatal pain‐related stress, the development of functional brain activity, and school‐age cognitive outcome in these vulnerable children.

Altered long-range alpha-band synchronization during visual short-term memory retention in children born very preterm

Children born very preterm, even when intelligence is broadly normal, often experience selective difficulties in executive function and visual-spatial processing. Development of structural cortical connectivity is known to be altered in this group, and functional magnetic resonance imaging (fMRI) evidence indicates that very preterm children recruit different patterns of functional connectivity between cortical regions during cognition. Synchronization of neural oscillations across brain areas has been proposed as a mechanism for dynamically assigning functional coupling to support perceptual and cognitive processing, but little is known about what role oscillatory synchronization may play in the altered neurocognitive development of very preterm children. To investigate this, we recorded magnetoencephalographic (MEG) activity while 7-8 year old children born very preterm and age-matched full-term controls performed a visual short-term memory task. Very preterm children exhibited reduced long-range synchronization in the alpha-band during visual short-term memory retention, indicating that cortical alpha rhythms may play a critical role in altered patterns functional connectivity expressed by this population during cognitive and perceptual processing. Long-range alpha-band synchronization was also correlated with task performance and visual-perceptual ability within the very preterm group, indicating that altered alpha oscillatory mechanisms mediating transient functional integration between cortical regions may be relevant to selective problems in neurocognitive development in this vulnerable population at school age.

Changes in mu rhythm during action observation and execution in adults with Down syndrome : Implications for action representation

The human mirror neuron system is thought to be the underlying basis of perception-action coupling involved in imitation and action understanding. In order to examine this issue we examined the recruitment of the mirror neuron system, as reflected in mu rhythm suppression in a population of adults with Down syndrome (DS) with known strengths in imitation but with impairments in perceptual-motor coupling. Ten healthy adults and 10 age-matched adults with (DS) participated in the study. Subjects were asked to make self-paced movements (execution), and view movements made by the experimenter (observation). The action consisted of reaching with the dominant hand to grasp and lift a cup. Cortical responses were recorded with a whole head magnetoencephalography (MEG) system. Both groups demonstrated significant attenuation of the mu rhythm in bilateral sensorimotor areas when executing the action. Typical adults also demonstrated significant mu suppression in bilateral sensorimotor areas during observation of the action. In contrast, when observing the movement, adults with DS showed a significantly reduced overall attenuation of mu activity with a distinct laterality in the pattern of mu suppression. These results suggest that there is a dysfunction in the execution/observation matching system in adults with DS and has implications for the functional role of the human mirror neuron system.

Magnetoencephalography Reveals Slowing of Resting Peak Oscillatory Frequency in Children Born Very Preterm

Resting cortical activity is characterized by a distinct spectral peak in the alpha frequency range. Slowing of this oscillatory peak toward the upper theta-band has been associated with a variety of neurological and neuropsychiatric conditions and has been attributed to altered thalamocortical dynamics. Children born very preterm exhibit altered development of thalamocortical systems. To test the hypothesis that peak oscillatory frequency is slowed in children born very preterm, we recorded resting magnetoencephalography (MEG) from school age children born very preterm (≤32 wk gestation) without major intellectual or neurological impairment and age-matched full-term controls. Very preterm children exhibit a slowing of peak frequency toward the theta-band over bilateral frontal cortex, together with reduced alpha-band power over bilateral frontal and temporal cortex, suggesting that mildly dysrhythmic thalamocortical interactions may contribute to altered spontaneous cortical activity in children born very preterm.

Application of multi-source minimum variance beamformers for reconstruction of correlated neural activity.

Linearly constrained minimum variance beamformers are highly effective for analysis of weakly correlated brain activity, but their performance degrades when correlations become significant. Multiple constrained minimum variance (MCMV) beamformers are insensitive to source correlations but require a priori information about the source locations. Besides the question whether unbiased estimates of source positions and orientations can be obtained remained unanswered. In this work, we derive MCMV-based source localizers that can be applied to both induced and evoked brain activity. They may be regarded as a generalization of scalar minimum-variance beamformers for the case of multiple correlated sources. We show that for arbitrary noise covariance these beamformers provide simultaneous unbiased estimates of multiple source positions and orientations and remain bounded at singular points. We also propose an iterative search algorithm that makes it possible to find sources approximately without a priori assumptions about their locations and orientations. Simulations and analyses of real MEG data demonstrate that presented approach is superior to traditional single-source beamformers in situations where correlations between the sources are significant.

Spatial-temporal dynamics of cortical activity underlying reaching and grasping

How humans understand the actions and intentions of others remains poorly understood. Here we report the results of a magnetoencephalography (MEG) experiment to determine the temporal dynamics and spatial distribution of brain regions activated during execution and observation of a reach to grasp motion using real world stimuli. We show that although both conditions activate similar brain areas, there are distinct differences in the timing, pattern and location of activation. Specifically, observation of motion revealed a right hemisphere dominance with activation involving a network of regions that include frontal, temporal and parietal areas. In addition, the latencies of activation showed a task specific pattern. During movement execution, the earliest activation was observed in the left premotor and somatosensory regions, followed closely by left primary motor and STG at the time of movement onset. During observation, there was a shift in the timing of activation with the earliest activity occurring in the right temporal region followed by activity in the left motor areas. Activity within these areas was also characterized by a shift to a lower frequency in comparison with action execution. These results add to the growing body of evidence indicating a complex interaction within a distributed network involving motor and nonmotor regions during observation of real actions. Hum Brain Mapp, 2010.

Region-Specific Slowing of Alpha Oscillations is Associated with Visual-Perceptual Abilities in Children Born Very Preterm

Children born very preterm (≤32 weeks gestational age) without major intellectual or neurological impairments often express selective deficits in visual-perceptual abilities. The alterations in neurophysiological development underlying these problems, however, remain poorly understood. Recent research has indicated that spontaneous alpha oscillations are slowed in children born very preterm, and that atypical alpha-mediated functional network connectivity may underlie selective developmental difficulties in visual-perceptual ability in this group. The present study provides the first source-resolved analysis of slowing of spontaneous alpha oscillations in very preterm children, indicating alterations in a distributed set of brain regions concentrated in areas of posterior parietal and inferior temporal regions associated with visual perception, as well as prefrontal cortical regions and thalamus. We also uniquely demonstrate that slowing of alpha oscillations is associated with selective difficulties in visual-perceptual ability in very preterm children. These results indicate that region-specific slowing of alpha oscillations contribute to selective developmental difficulties prevalent in this population.

Multi-core beamformers: derivation, limitations and improvements

Minimum variance beamformers are popular tools used in EEG and MEG for analysis of brain activity. In recent years new multi-source beamformer methods were developed, including the Dual-Core Beamformer (DCBF) and its enhanced version (eDCBF). Both techniques should allow modeling of correlated brain activity under a wide range of conditions. However, the mathematical justification given is based on single-source results and computer simulations, which do not provide an insight into the assumptions involved and the limits of their applicability. Current work addresses this problem. Analytical expressions relating actual source parameters to those obtained with the DCBF and eDCBF are derived, and rigorous conclusions regarding the accuracy of the DCBF/eDCBF reconstructions are made. In particular, it is shown that DCBF accurately identifies source coordinates, but amplitudes and orientations are only correct for high SNRs and fully correlated sources. In contrast, eDCBF source localization is inaccurate, but if the source positions are found precisely, eDCBF allows perfect reconstruction for arbitrary SNRs. If the source positions are approximate, the reconstruction errors are generally larger for higher SNR values. The eDCBF results can be improved by using global unbiased localizer functions and an alternative way of estimating source orientations.

Altered Long-Range Phase Synchronization and Cortical Activation in Children Born Very Preterm

Children born very preterm, even with broadly normal IQ, commonly show selective difficulties in visuospatial processing and executive functioning. Very little, however, is known what alterations in cortical processing underlie these deficits. We recorded MEG while eight children born very preterm (≤32 weeks gestational age) and eight full-term controls performed a visual short-term memory task at mean age 7.5 years (range 6.4 - 8.4). Previously, we demonstrated increased long-range alpha and beta band phase synchronization between MEG sensors during STM retention in a group of 17 full-term children age 6-10 years. Here we present preliminary evidence that long-range phase synchronization in very preterm children, relative to controls, is reduced in the alpha-band but increased in the theta-band. In addition, we investigated cortical activation during STM retention employing synthetic aperture magnetometry (SAM) beamformer to localize changes in gamma-band power. Preliminary results indicate sequential activation of occipital, parietal and frontal cortex in control children, as well as reduced activation in very preterm children relative to controls. These preliminary results suggest that children born very preterm exhibit altered inter-regional functional connectivity and cortical activation during cognitive processing.

A variational Bayes spatiotemporal model for electromagnetic brain mapping

In this article, we present a new variational Bayes approach for solving the neuroelectromagnetic inverse problem arising in studies involving electroencephalography (EEG) and magnetoencephalography (MEG). This high-dimensional spatiotemporal estimation problem involves the recovery of time-varying neural activity at a large number of locations within the brain, from electromagnetic signals recorded at a relatively small number of external locations on or near the scalp. Framing this problem within the context of spatial variable selection for an underdetermined functional linear model, we propose a spatial mixture formulation where the profile of electrical activity within the brain is represented through location-specific spike-and-slab priors based on a spatial logistic specification. The prior specification accommodates spatial clustering in brain activation, while also allowing for the inclusion of auxiliary information derived from alternative imaging modalities, such as functional magnetic resonance imaging (fMRI). We develop a variational Bayes approach for computing estimates of neural source activity, and incorporate a nonparametric bootstrap for interval estimation. The proposed methodology is compared with several alternative approaches through simulation studies, and is applied to the analysis of a multimodal neuroimaging study examining the neural response to face perception using EEG, MEG, and fMRI.