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.
faces; inhibition; language; connectivity; ASD; preterm; developmental cognitive neuroscience; magnetoencephalography
Impaired social interaction is one of the hallmarks of Autism Spectrum Disorder (ASD). Emotional faces are arguably the most critical visual social stimuli and the ability to perceive, recognize, and interpret emotions is central to social interaction and communication, and subsequently healthy social development. However, our understanding of the neural and cognitive mechanisms underlying emotional face processing in adolescents with ASD is limited. We recruited 48 adolescents, 24 with high functioning ASD and 24 typically developing controls. Participants completed an implicit emotional face processing task in the MEG. We examined spatiotemporal differences in neural activation between the groups during implicit angry and happy face processing. While there were no differences in response latencies between groups across emotions, adolescents with ASD had lower accuracy on the implicit emotional face processing task when the trials included angry faces. MEG data showed atypical neural activity in adolescents with ASD during angry and happy face processing, which included atypical activity in the insula, anterior and posterior cingulate and temporal and orbitofrontal regions. Our findings demonstrate differences in neural activity during happy and angry face processing between adolescents with and without ASD. These differences in activation in social cognitive regions may index the difficulties in face processing and in comprehension of social reward and punishment in the ASD group. Thus, our results suggest that atypical neural activation contributes to impaired affect processing, and thus social cognition, in adolescents with ASD.
•The ability to recognize and interpret emotions is central to social interaction.•Deficits in social interactions are hallmarks of autism spectrum disorder (ASD).•Adolescents with and without ASD completed an emotional face task in MEG.•MEG data showed atypical neural activity in ASD to both angry and happy faces.•Insula, cingulate, temporal and orbitofrontal activities were particularly affected in the ASD group.
Implicit face processing; Adolescents; Autism Spectrum Disorder; Magnetoencephalography; Affect processing; Anterior cingulate cortex
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social cognition. The biological basis of deficits in social cognition in ASD, and their difficulty in processing emotional face information in particular, remains unclear. Atypical communication within and between brain regions has been reported in ASD. Interregional phase-locking is a neurophysiological mechanism mediating communication among brain areas and is understood to support cognitive functions. In the present study we investigated interregional magnetoencephalographic phase synchronization during the perception of emotional faces in adolescents with ASD.
A total of 22 adolescents with ASD (18 males, mean age =14.2 ± 1.15 years, 22 right-handed) with mild to no cognitive delay and 17 healthy controls (14 males, mean age =14.4 ± 0.33 years, 16 right-handed) performed an implicit emotional processing task requiring perception of happy, angry and neutral faces while we recorded neuromagnetic signals. The faces were presented rapidly (80 ms duration) to the left or right of a central fixation cross and participants responded to a scrambled pattern that was presented concurrently on the opposite side of the fixation point. Task-dependent interregional phase-locking was calculated among source-resolved brain regions.
Task-dependent increases in interregional beta synchronization were observed. Beta-band interregional phase-locking in adolescents with ASD was reduced, relative to controls, during the perception of angry faces in a distributed network involving the right fusiform gyrus and insula. No significant group differences were found for happy or neutral faces, or other analyzed frequency ranges. Significant reductions in task-dependent beta connectivity strength, clustering and eigenvector centrality (all P <0.001) in the right insula were found in adolescents with ASD, relative to controls.
Reduced beta synchronization may reflect inadequate recruitment of task-relevant networks during emotional face processing in ASD. The right insula, specifically, was a hub of reduced functional connectivity and may play a prominent role in the inability to effectively extract emotional information from faces. These findings suggest that functional disconnection in brain networks mediating emotional processes may contribute to deficits in social cognition in this population.
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Functional connectivity; Autism spectrum disorders; Affect processing; Neural oscillation; Magnetoencephalography; Social cognition; Neural synchrony; Beta-band; Graph theory; Cognitive development; Face processing
Recent evidence suggests that disruption of integrative processes in sensation and perception may play a critical role in cognitive and behavioural atypicalities characteristic of ASD. In line with this, ASD is associated with altered structural and functional brain connectivity and atypical patterns of inter-regional communication which have been proposed to contribute to cognitive difficulties prevalent in this group. The present MEG study used atlas-guided source space analysis of inter-regional phase synchronization in ASD participants, as well as matched typically developing controls, during a dot number estimation task. This task included stimuli with globally integrated forms (animal shapes) as well as randomly-shaped stimuli which lacked a coherent global pattern. Early task-dependent increases in inter-regional phase synchrony in theta, alpha and beta frequency bands were observed. Reduced long-range beta-band phase synchronization was found in participants with ASD at 70–145 ms during presentation of globally coherent dot patterns. This early reduction in task-dependent inter-regional connectivity encompassed numerous areas including occipital, parietal, temporal, and frontal lobe regions. These results provide the first evidence for inter-regional phase synchronization during numerosity estimation, as well as its alteration in ASD, and suggest that problems with communication among brain areas may contribute to difficulties with integrative processes relevant to extraction of meaningful ‘Gestalt’ features in this population.
•MEG synchronization in ASD was investigated during number estimation.•Number estimation was associated with synchronization in theta, alpha & beta bands.•Adolescents with ASD showed reduced beta synchrony for processing of coherent images.
Autism spectrum disorder; Beta band; Feature integration; Neural oscillations; Neural synchrony; Numerosity
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.
PMID: 24976782 CAMSID: cams3899
Emotional face processing; Eye gaze processing; Social attention
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.
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.
Autism spectrum disorder; Adolescence; Brain imaging; Inhibition
Research on the neural bases of cognitive deficits in autism spectrum disorder (ASD) has shown that working memory (WM) difficulties are associated with abnormalities in the prefrontal cortex. However, cognitive load impacts these findings, and no studies have examined the relation between WM load and neural underpinnings in children with ASD. Thus, the current study determined the effects of cognitive load on WM, using a visuo-spatial WM capacity task in children with and without ASD with functional magnetic resonance imaging (fMRI).
We used fMRI and a 1-back colour matching task (CMT) task with four levels of difficulty to compare the cortical activation patterns associated with WM in children (7–13 years old) with high functioning autism (N = 19) and matched controls (N = 17) across cognitive load.
Performance on CMT was comparable between groups, with the exception of one difficulty level. Using linear trend analyses, the control group showed increasing activation as a function of difficulty level in frontal and parietal lobes, particularly between the highest difficulty levels, and decreasing activation as a function of difficulty level in the posterior cingulate and medial frontal gyri. In contrast, children with ASD showed increasing activation only in posterior brain regions and decreasing activation in the posterior cingulate and medial frontal gyri, as a function of difficulty level. Significant differences were found in the precuneus, dorsolateral prefrontal cortex and medial premotor cortex, where control children showed greater positive linear relations between cortical activity and task difficulty level, particularly at the highest difficulty levels, but children with ASD did not show these trends.
Children with ASD showed differences in activation in the frontal and parietal lobes—both critical substrates for visuo-spatial WM. Our data suggest that children with ASD rely mainly on posterior brain regions associated with visual and lower level processing, whereas controls showed activity in frontal lobes related to the classic WM network. Findings will help guide future work by localizing areas of vulnerability to developmental disturbances.
Working memory; Autism spectrum disorder; Functional magnetic resonance imaging; Executive function; Cognitive load; Frontal lobe; Parietal lobe
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.
Autism spectrum disorders; Structural MRI; Cortical thickness; Social impairment; Developmental changes
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.
Default mode; difficulty; fMRI; working memory
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.
color-word Stroop; orthographic manipulation; children; interference; facilitation
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.
ASD; autism; neural synchrony; neural oscillation; magnetoencephalography; set-shifting; executive function; functional connectivity
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.
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.
stuttering; child development; speech-motor control; auditory processing; M50; magnetic source imaging
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.
development; amygdala; fMRI; face processing; social-emotional processing
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.
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.