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1.  Neuromagnetic Vistas into Typical and Atypical Development of Frontal Lobe Functions 
The frontal lobes are involved in many higher-order cognitive functions such as social cognition executive functions and language and speech. These functions are complex and follow a prolonged developmental course from childhood through to early adulthood. Magnetoencephalography (MEG) is ideal for the study of development of these functions, due to its combination of temporal and spatial resolution which allows the determination of age-related changes in both neural timing and location. There are several challenges for MEG developmental studies: to design tasks appropriate to capture the neurodevelopmental trajectory of these cognitive functions, and to develop appropriate analysis strategies to capture various aspects of neuromagnetic frontal lobe activity. Here, we review our MEG research on social and executive functions, and speech in typically developing children and in two clinical groups – children with autism spectrum disorder and children born very preterm. The studies include facial emotional processing, inhibition, visual short-term memory, speech production, and resting-state networks. We present data from event-related analyses as well as on oscillations and connectivity analyses and review their contributions to understanding frontal lobe cognitive development. We also discuss the challenges of testing young children in the MEG and the development of age-appropriate technologies and paradigms.
PMCID: PMC4061489  PMID: 24994980
faces; inhibition; language; connectivity; ASD; preterm; developmental cognitive neuroscience; magnetoencephalography
2.  Is it in the eyes? Dissociating the role of emotion and perceptual features of emotionally expressive faces in modulating orienting to eye gaze 
Visual cognition  2011;19(4):483-510.
This study investigated the role of the eye region of emotional facial expressions in modulating gaze orienting effects. Eye widening is characteristic of fearful and surprised expressions and may significantly increase the salience of perceived gaze direction. This perceptual bias rather than the emotional valence of certain expressions may drive enhanced gaze orienting effects. In a series of three experiments involving low anxiety participants, different emotional expressions were tested using a gaze-cueing paradigm. Fearful and surprised expressions enhanced the gaze orienting effect compared with happy or angry expressions. Presenting only the eye regions as cueing stimuli eliminated this effect whereas inversion globally reduced it. Both inversion and the use of eyes only attenuated the emotional valence of stimuli without affecting the perceptual salience of the eyes. The findings thus suggest that low-level stimulus features alone are not sufficient to drive gaze orienting modulations by emotion. Rather, they interact with the emotional valence of the expression that appears critical. The study supports the view that rapid processing of fearful and surprised emotional expressions can potentiate orienting to another person’s averted gaze in non-anxious people.
PMCID: PMC4072640  PMID: 24976782 CAMSID: cams3899
Emotional face processing; Eye gaze processing; Social attention
3.  Temporal-Spatial Neural Activation Patterns Linked to Perceptual Encoding of Emotional Salience 
PLoS ONE  2014;9(4):e93753.
It is well known that we continuously filter incoming sensory information, selectively allocating attention to what is important while suppressing distracting or irrelevant information. Yet questions remain about spatiotemporal patterns of neural processes underlying attentional biases toward emotionally significant aspects of the world. One index of affectively biased attention is an emotional variant of an attentional blink (AB) paradigm, which reveals enhanced perceptual encoding for emotionally salient over neutral stimuli under conditions of limited executive attention. The present study took advantage of the high spatial and temporal resolution of magnetoencephalography (MEG) to investigate neural activation related to emotional and neutral targets in an AB task. MEG data were collected while participants performed a rapid stimulus visual presentation task in which two target stimuli were embedded in a stream of distractor words. The first target (T1) was a number and the second (T2) either an emotionally salient or neutral word. Behavioural results replicated previous findings of greater accuracy for emotionally salient than neutral T2 words. MEG source analyses showed that activation in orbitofrontal cortex, characterized by greater power in the theta and alpha bands, and dorsolateral prefrontal activation were associated with successful perceptual encoding of emotionally salient relative to neutral words. These effects were observed between 250 and 550 ms, latencies associated with discrimination of perceived from unperceived stimuli. These data suggest that important nodes of both emotional salience and frontoparietal executive systems are associated with the emotional modulation of the attentional blink.
PMCID: PMC3984101  PMID: 24727751
4.  Is inhibitory control a ‘no-go’ in adolescents with autism spectrum disorder? 
Molecular Autism  2014;5:6.
Autism spectrum disorder (ASD) refers to a range of neurodevelopmental conditions characterized by social communication deficits, repetitive behaviours, and restrictive interests. Impaired inhibition has been suggested to exacerbate the core symptoms of ASD. This is particularly critical during adolescence when social skills are maturing to adult levels. Using magnetoencephalography (MEG), we identified the location and timing pattern of neural activity associated with inhibition in adolescents with autism, compared to typically developing adolescents.
The MEG data from 15 adolescents with ASD and 15 age-matched controls (13 to 17 years) were collected during a go/no-go task with inverse ratios of go/no-go trials in two conditions: an inhibition condition (1:2) and a baseline condition (2:1). No-go trials from the two conditions were analyzed using beamformer source localizations from 200 ms to 400 ms post-stimulus onset. Significant activations were determined using permutation testing.
Adolescents with ASD recruited first the right middle frontal gyrus (200 to 250 ms) followed by the left postcentral gyrus (250 to 300 ms) and finally the left middle frontal and right medial frontal gyri (300 to 400 ms). Typically developing adolescents recruited first the left middle frontal gyrus (200 to 250 ms), followed by the left superior and inferior frontal gyri (250 to 300 ms), then the right middle temporal gyrus (300 to 350 ms), and finally the superior and precentral gyri and right inferior lobule (300 to 400 ms).
Adolescents with ASD showed recruitment limited largely to the frontal cortex unlike typically developing adolescents who recruited parietal and temporal regions as well. These findings support the presence of an atypical, restricted inhibitory network in adolescents with ASD compared to controls.
PMCID: PMC3939401  PMID: 24485230
Autism spectrum disorder; Adolescence; Brain imaging; Inhibition
6.  Effects of age and symptomatology on cortical thickness in autism spectrum disorders 
Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with ASD, between the ages of 7 and 39 years in comparison to typically developing controls. Additionally, we examined differences in cortical thickness in relation to symptomatology in the ASD group, and their association with age. Analyses were conducted using a general linear model, controlling for sex. Social and communication scores from the Autism Diagnostic Interview-Revised (ADI-R) were correlated with the thickness of regions implicated in those functions. Controls showed widespread cortical thinning relative to the ASD group. Within regions-of-interest, increased thickness in the rostral anterior cingulate cortex was associated with poorer social scores. Additionally, a significant interaction between age and social impairment was found in the orbitofrontal cortex, with more impaired younger children having decreased thickness in this region. These results suggest that differential neurodevelopmental trajectories are present in individuals with ASD and some differences are associated with diagnostic behaviours.
PMCID: PMC3652338  PMID: 23678367
Autism spectrum disorders; Structural MRI; Cortical thickness; Social impairment; Developmental changes
7.  A balancing act of the brain: activations and deactivations driven by cognitive load 
Brain and Behavior  2013;3(3):273-285.
The majority of neuroimaging studies focus on brain activity during performance of cognitive tasks; however, some studies focus on brain areas that activate in the absence of a task. Despite the surge of research comparing these contrasted areas of brain function, their interrelation is not well understood. We systematically manipulated cognitive load in a working memory task to examine concurrently the relation between activity elicited by the task versus activity during control conditions. We presented adults with six levels of task demand, and compared those with three conditions without a task. Using whole-brain analysis, we found positive linear relations between cortical activity and task difficulty in areas including middle frontal gyrus and dorsal cingulate; negative linear relations were found in medial frontal gyrus and posterior cingulate. These findings demonstrated balancing of activation patterns between two mental processes, which were both modulated by task difficulty. Frontal areas followed a graded pattern more closely than other regions. These data also showed that working memory has limited capacity in adults: an upper bound of seven items and a lower bound of four items. Overall, working memory and default-mode processes, when studied concurrently, reveal mutually competing activation patterns.
PMCID: PMC3683287  PMID: 23785659
Default mode; difficulty; fMRI; working memory
8.  “I Can Read These Colors.” Orthographic Manipulations and the Development of the Color-Word Stroop 
The color-word Stroop is a popular measure in psychological assessments. Evidence suggests that Stroop performance relies heavily on reading, an ability that improves over childhood. One way to influence reading proficiency is by orthographic manipulations. To determine the degree of interference posed by orthographic manipulations with development, in addition to standard color-Words (purple) we manipulated letter-positions: First/last letter in correct place (prulpe) and Scrambled (ulrpep). We tested children 7–16 years (n = 128) and adults (n = 23). Analyses showed that Word- and First/last-incongruent were qualitatively similar, whereas Word-congruent was different than other conditions. Results suggest that for children and adults, performance was hindered the most for incongruent and incorrectly spelled words and was most facilitated when words were congruent with the ink color and correctly spelled. Implications on visual word recognition and reading are discussed.
PMCID: PMC3539116  PMID: 23316179
color-word Stroop; orthographic manipulation; children; interference; facilitation
9.  Reduced Theta Connectivity during Set-Shifting in Children with Autism 
Autism spectrum disorder (ASD) is a characterized by deficits in social cognition and executive function. An area of particular difficulty for children with ASD is cognitive flexibility, such as the ability to shift between attentional or response sets. The biological basis of such deficits remains poorly understood, although atypical development of structural and functional brain connectivity have been reported in ASD, suggesting that disruptions of normal patterns of inter-regional communication may contribute to cognitive problems in this group. The present magnetoencephalography study measured inter-regional phase synchronization while children with ASD and typically developing matched controls (6–14 years of age) performed a set-shifting task. Reduced theta-band phase synchronization was observed in children with ASD during extradimensional set-shifting. This reduction in task-dependent inter-regional connectivity encompassed numerous areas including multiple frontal lobe regions, and indicates that problems with communication among brain areas may contribute to difficulties with executive function in ASD.
PMCID: PMC3827625  PMID: 24294201
ASD; autism; neural synchrony; neural oscillation; magnetoencephalography; set-shifting; executive function; functional connectivity
10.  Disruption of Rolandic Gamma-Band Functional Connectivity by Seizures is Associated with Motor Impairments in Children with Epilepsy 
PLoS ONE  2012;7(6):e39326.
Although children with epilepsy exhibit numerous neurological and cognitive deficits, the mechanisms underlying these impairments remain unclear. Synchronization of oscillatory neural activity in the gamma frequency range (>30 Hz) is purported to be a mechanism mediating functional integration within neuronal networks supporting cognition, perception and action. Here, we tested the hypothesis that seizure-induced alterations in gamma synchronization are associated with functional deficits. By calculating synchrony among electrodes and performing graph theoretical analysis, we assessed functional connectivity and local network structure of the hand motor area of children with focal epilepsy from intracranial electroencephalographic recordings. A local decrease in inter-electrode phase synchrony in the gamma bands during ictal periods, relative to interictal periods, within the motor cortex was strongly associated with clinical motor weakness. Gamma-band ictal desychronization was a stronger predictor of deficits than the presence of the seizure-onset zone or lesion within the motor cortex. There was a positive correlation between the magnitude of ictal desychronization and impairment of motor dexterity in the contralateral, but not ipsilateral hand. There was no association between ictal desynchronization within the hand motor area and non-motor deficits. This study uniquely demonstrates that seizure-induced disturbances in cortical functional connectivity are associated with network-specific neurological deficits.
PMCID: PMC3380842  PMID: 22737233
11.  Speech-induced suppression of evoked auditory fields in children who stutter 
NeuroImage  2010;54(4):2994-3003.
Auditory responses to speech sounds that are self-initiated are suppressed compared to responses to the same speech sounds during passive listening. This phenomenon is referred to as speech-induced suppression, a potentially important feedback-mediated speech-motor control process. In an earlier study, we found that both adults who do and do not stutter demonstrated reduced amplitude of the auditory M50 and M100 responses to speech during active production relative to passive listening. It is unknown if auditory responses to self-initiated speech-motor acts are suppressed in children or if the phenomenon differs between children who do and do not stutter. As stuttering is a developmental speech disorder, examining speech-induced suppression in children may identify possible neural differences underlying stuttering close to its time of onset. We used magnetoencephalography to determine the presence of speech-induced suppression in children and to characterize the properties of speech-induced suppression in children who stutter. We examined the auditory M50 as this was the earliest robust response reproducible across our child participants and the most likely to reflect a motor-to-auditory relation. Both children who do and do not stutter demonstrated speech-induced suppression of the auditory M50. However, children who stutter had a delayed auditory M50 peak latency to vowel sounds compared to children who do not stutter indicating a possible deficiency in their ability to efficiently integrate auditory speech information for the purpose of establishing neural representations of speech sounds.
PMCID: PMC3042852  PMID: 21095231
stuttering; child development; speech-motor control; auditory processing; M50; magnetic source imaging
12.  The changing face of emotion: age-related patterns of amygdala activation to salient faces 
The present study investigated age-related differences in the amygdala and other nodes of face-processing networks in response to facial expression and familiarity. fMRI data were analyzed from 31 children (3.5–8.5 years) and 14 young adults (18–33 years) who viewed pictures of familiar (mothers) and unfamiliar emotional faces. Results showed that amygdala activation for faces over a scrambled image baseline increased with age. Children, but not adults, showed greater amygdala activation to happy than angry faces; in addition, amygdala activation for angry faces increased with age. In keeping with growing evidence of a positivity bias in young children, our data suggest that children find happy faces to be more salient or meaningful than angry faces. Both children and adults showed preferential activation to mothers’ over strangers’ faces in a region of rostral anterior cingulate cortex associated with self-evaluation, suggesting that some nodes in frontal evaluative networks are active early in development. This study presents novel data on neural correlates of face processing in childhood and indicates that preferential amygdala activation for emotional expressions changes with age.
PMCID: PMC3023079  PMID: 20194512
development; amygdala; fMRI; face processing; social-emotional processing
13.  Review of neuroimaging in autism spectrum disorders: what have we learned and where we go from here 
Molecular Autism  2011;2:4.
Autism spectrum disorder (ASD) refers to a syndrome of social communication deficits and repetitive behaviors or restrictive interests. It remains a behaviorally defined syndrome with no reliable biological markers. The goal of this review is to summarize the available neuroimaging data and examine their implication for our understanding of the neurobiology of ASD.
Although there is variability in the literature on structural magnetic resonance literature (MRI), there is evidence of volume abnormalities in both grey and white matter, with a suggestion of some region-specific differences. Early brain overgrowth is probably the most replicated finding in a subgroup of people with ASD, and new techniques, such as cortical-thickness measurements and surface morphometry have begun to elucidate in more detail the patterns of abnormalities as they evolve with age, and are implicating specific neuroanatomical or neurodevelopmental processes. Functional MRI and diffusion tensor imaging techniques suggest that such volume abnormalities are associated with atypical functional and structural connectivity in the brain, and researchers have begun to use magnetic resonance spectroscopy (MRS) techniques to explore the neurochemical substrate of such abnormalities. The data from multiple imaging methods suggests that ASD is associated with an atypically connected brain. We now need to further clarify such atypicalities, and start interpreting them in the context of what we already know about typical neurodevelopmental processes including migration and organization of the cortex. Such an approach will allow us to relate imaging findings not only to behavior, but also to genes and their expression, which may be related to such processes, and to further our understanding of the nature of neurobiologic abnormalities in ASD.
PMCID: PMC3102613  PMID: 21501488
14.  Top-down and bottom-up modulation in processing bimodal face/voice stimuli 
BMC Neuroscience  2010;11:36.
Processing of multimodal information is a critical capacity of the human brain, with classic studies showing bimodal stimulation either facilitating or interfering in perceptual processing. Comparing activity to congruent and incongruent bimodal stimuli can reveal sensory dominance in particular cognitive tasks.
We investigated audiovisual interactions driven by stimulus properties (bottom-up influences) or by task (top-down influences) on congruent and incongruent simultaneously presented faces and voices while ERPs were recorded. Subjects performed gender categorisation, directing attention either to faces or to voices and also judged whether the face/voice stimuli were congruent in terms of gender. Behaviourally, the unattended modality affected processing in the attended modality: the disruption was greater for attended voices. ERPs revealed top-down modulations of early brain processing (30-100 ms) over unisensory cortices. No effects were found on N170 or VPP, but from 180-230 ms larger right frontal activity was seen for incongruent than congruent stimuli.
Our data demonstrates that in a gender categorisation task the processing of faces dominate over the processing of voices. Brain activity showed different modulation by top-down and bottom-up information. Top-down influences modulated early brain activity whereas bottom-up interactions occurred relatively late.
PMCID: PMC2850913  PMID: 20222946

Results 1-14 (14)