Developmental trajectory of face processing revealed by integrative dynamics.

Given their unique connectivity, a primary function of brain networks must be to transfer and integrate information. Therefore, the way in which information is integrated by individual nodes of the network may be an informative aspect of cognitive processing. Here we present a method inspired by telecommunications research that utilizes time-frequency fluctuations of neural activity to infer how information is integrated by individual nodes of the network. We use a queueing theoretical model to interpret empirical data in terms of information processing and integration. In particular, we demonstrate, in participants aged from 6 to 41 years, that the well-known face inversion phenomenon may be explained in terms of information integration. Our model suggests that inverted faces may be associated with shorter and more frequent neural integrative stages, indicating fractured processing and consistent with the notion that inverted faces are perceived by parts. Conversely, our model suggests that upright faces may be associated with a smaller number of sustained episodes of integration, indicating more involved processing, akin to holistic and configural processing. These differences in how upright and inverted faces are processed became more pronounced during development, indicating a gradual specialization for face perception. These effects were robustly expressed in the right fusiform gyrus (all groups), as well as right parahippocampal gyrus (children and adolescents only) and left inferior temporal cortex (adults only).

MEG measures of covert orienting and gaze processing in children.

We investigated developmental differences in the cortical attention processing network using magnetoencephalography (MEG) and a spatial cueing task in 7-8 and 12-13 year old children. The cueing paradigm consisted of a centrally presented face with left or right averted eye-gaze in the gaze cue condition, and a central face with straight gaze presented with a cue stimulus to the left or right of the face in the peripheral cue condition. Cue congruency was 50 %. MEG was recorded during the two conditions and event-related beamforming was used to determine the timing and location of the brain activity related to target detection with the two types of cueing. The MEG data showed no age differences in the eye-gaze condition, but a developmental difference characterised by slower and more diffuse activations for peripheral cues in the younger versus the older age group. In the 7-8 year olds activation peaked around 300 ms, and was localised to left inferior frontal gyrus as well as posterior areas related to visuo-spatial processing. The 12-13 year olds showed a temporoparietal pattern of activation characteristic of spatial reorientation which resembled that seen for adult participants using the same paradigm (Nagata et al. 2012). The activation peaked around 200 ms and was localised to the left superior frontal gyrus, middle frontal gyrus but bilaterally near the temporoparietal junction. The data indicate maturational changes in brain activity for peripheral cueing.

Techniques for detection and localization of weak hippocampal and medial frontal sources using beamformers in MEG.

Magnetoencephalography provides precise information about the temporal dynamics of brain activation and is an ideal tool for investigating rapid cognitive processing. However, in many cognitive paradigms visual stimuli are used, which evoke strong brain responses (typically 40-100 nAm in V1) that may impede the detection of weaker activations of interest. This is particularly a concern when beamformer algorithms are used for source analysis, due to artefacts such as "leakage" of activation from the primary visual sources into other regions. We have previously shown (Quraan et al. 2011) that we can effectively reduce leakage patterns and detect weak hippocampal sources by subtracting the functional images derived from the experimental task and a control task with similar stimulus parameters. In this study we assess the performance of three different subtraction techniques. In the first technique we follow the same post-localization subtraction procedures as in our previous work. In the second and third techniques, we subtract the sensor data obtained from the experimental and control paradigms prior to source localization. Using simulated signals embedded in real data, we show that when beamformers are used, subtraction prior to source localization allows for the detection of weaker sources and higher localization accuracy. The improvement in localization accuracy exceeded 10 mm at low signal-to-noise ratios, and sources down to below 5 nAm were detected. We applied our techniques to empirical data acquired with two different paradigms designed to evoke hippocampal and frontal activations, and demonstrated our ability to detect robust activations in both regions with substantial improvements over image subtraction. We conclude that removal of the common-mode dominant sources through data subtraction prior to localization further improves the beamformer's ability to project the n-channel sensor-space data to reveal weak sources of interest and allows more accurate localization.

Response inhibition in adults and teenagers: spatiotemporal differences in the prefrontal cortex.

Inhibition is a core executive function reliant on the frontal lobes that shows protracted maturation through to adulthood. We investigated the spatiotemporal characteristics of response inhibition during a visual go/no-go task in 14 teenagers and 14 adults using magnetoencephalography (MEG) and a contrast between two no-go experimental conditions designed to eliminate a common confound in earlier studies comparing go with no-go trials. Source analyses were performed using an event-related beamformer algorithm with co-registered individual structural MRIs. Performance was controlled to be similar across subjects. Analyses of MEG data revealed bilateral prefrontal activity in the inhibitory condition for both age groups, but with different spatiotemporal patterns: around 300ms after stimulus onset in middle frontal gyri in teenagers vs. around 260ms in inferior frontal gyri in adults. Moreover, the inhibition of a prepotent motor response showed a stronger recruitment of the left hemisphere in teenagers than in adults and of the right hemisphere in adults than in teenagers. These findings provide high-resolution temporal and spatial information regarding response inhibition in adolescents compared to adults, independent of motor components and performance differences.

Spatio-temporal localisation of attentional orienting to gaze and peripheral cues.

Another person's eye gaze often triggers our attention such that we follow their direction of gaze. We investigated how the neural mechanisms for processing eye-gaze and spatial attention interact using magnetoencephalography (MEG) in young adults. In a cueing paradigm, a face was presented centrally with left or right averted eye-gaze serving as the directional cue in the eye-gaze condition. In the peripheral cue condition, the face with a straight gaze was presented with a cue stimulus appearing on the left or right of the face. Cue validity was 50%. MEG was recorded during the two conditions and event-related beamforming was used to determine the timing and location of the brain activity related to the two types of cueing. The MEG data indicated that generally the network of activation in response to our two cue types was similar. In contrast, MEG responses to the targets demonstrated one main peak at 286-306 ms for the eye-gaze cue condition while two peaks were found at 238-258 ms and 286-306 ms for the peripheral cue condition. Activation was also consistently larger for the invalid than valid trials. Source images for the invalid minus valid contrasts for the 238-258 ms window showed significant activation only in the peripheral cueing condition, in the left temporoparietal junction and left inferior frontal gyrus. In the 286-306 ms window, both conditions showed left medial frontal activations. Thus, peripheral cues showed more rapid neural processing than the eye-gaze cues, with the second component being common to both, reflecting in part common processing. We suggest that attentional processing was maximal in the left hemisphere, as the right hemisphere was likely engaged in processing the face information.

Characterizing the normal developmental trajectory of expressive language lateralization using magnetoencephalography.

To characterize the developmental trajectory for expressive language representation and to test competing explanations for the relative neuroplasticity of language in childhood, we studied 28 healthy children and adolescents (aged 5-19 years) participating in a covert verb generation task in magnetoencephalography. Lateralization of neuromagnetic responses in the frontal lobe was quantified using a bootstrap statistical thresholding procedure for differential beamformer analyses. We observed a significant positive correlation between left hemisphere lateralization and age. Findings suggest that adult-typical left hemisphere lateralization emerges from an early bilateral language network, which may explain the pediatric advantage for interhemispheric plasticity of language.

The development of face recognition; hippocampal and frontal lobe contributions determined with MEG.

Face recognition skills improve steadily across childhood, yet few studies have investigated the development of the neural sources underlying these processes. We investigated the developmental changes in brain activity related specifically to face recognition, using magnetoencephalography (MEG). We studied 70 children (6-19 years) and 20 young adults. Photographs of 240 neutral faces were used in two blocks of 1-back recognition tasks; one block contained faces upright and in the other block, faces were presented inverted. MEG activity was recorded on a 151 sensor CTF/MISL system. A structural MRI was acquired for all subjects. We focussed on the repetition effects of the faces, in a 280-680 ms window, contrasting the repeated faces with the first presentation of the faces. The analyses showed reliable right hippocampal activation across all age groups, and a right inferior frontal activation that emerged for repeated, recognised faces at 10-11 years of age. The hippocampi are implicated in memory function and we demonstrate that the right hippocampus is specifically involved for face recognition. Further, we determined that this comes on-line by early school age, which is consistent with the known early maturation of the hippocampi. In contrast, we show that the right inferior frontal areas do not come on-line until later in childhood, consistent with the protracted development of the frontal cortices. These data support the hypothesis that different age groups use different strategies and neural structures for face recognition.

Detection and localization of hippocampal activity using beamformers with MEG: a detailed investigation using simulations and empirical data.

The ability to detect neuronal activity emanating from deep brain structures such as the hippocampus using magnetoencephalography has been debated in the literature. While a significant number of recent publications reported activations from deep brain structures, others reported their inability to detect such activity even when other detection modalities confirmed its presence. In this article, we relied on realistic simulations to show that both sides of this debate are correct and that these findings are reconcilable. We show that the ability to detect such activations in evoked responses depends on the signal strength, the amount of brain noise background, the experimental design parameters, and the methodology used to detect them. Furthermore, we show that small signal strengths require contrasts with control conditions to be detected, particularly in the presence of strong brain noise backgrounds. We focus on one localization technique, the adaptive spatial filter (beamformer), and examine its strengths and weaknesses in reconstructing hippocampal activations, in the presence of other strong brain sources such as visual activations, and compare the performance of the vector and scalar beamformers under such conditions. We show that although a weight-normalized beamformer combined with a multisphere head model is not biased in the presence of uncorrelated random noise, it can be significantly biased in the presence of correlated brain noise. Furthermore, we show that the vector beamformer performs significantly better than the scalar under such conditions. We corroborate our findings empirically using real data and demonstrate our ability to detect and localize such sources.

Brain noise is task dependent and region specific.

The emerging organization of anatomical and functional connections during human brain development is thought to facilitate global integration of information. Recent empirical and computational studies have shown that this enhanced capacity for information processing enables a diversified dynamic repertoire that manifests in neural activity as irregularity and noise. However, transient functional networks unfold over multiple time, scales and the embedding of a particular region depends not only on development, but also on the manner in which sensory and cognitive systems are engaged. Here we show that noise is a facet of neural activity that is also sensitive to the task context and is highly region specific. Children (6-16 yr) and adults (20-41 yr) performed a one-back face recognition task with inverted and upright faces. Neuromagnetic activity was estimated at several hundred sources in the brain by applying a beamforming technique to the magnetoencephalogram (MEG). During development, neural activity became more variable across the whole brain, with most robust increases in medial parietal regions, such as the precuneus and posterior cingulate cortex. For young children and adults, activity evoked by upright faces was more variable and noisy compared with inverted faces, and this effect was reliable only in the right fusiform gyrus. These results are consistent with the notion that upright faces engender a variety of integrative neural computations, such as the relations among facial features and their holistic constitution. This study shows that transient changes in functional integration modulated by task demand are evident in the variability of regional neural activity.

Feature-space-based FMRI analysis using the optimal linear transformation.

The optimal linear transformation (OLT), an image analysis technique of feature space, was first presented in the field of MRI. This paper proposes a method of extending OLT from MRI to functional MRI (fMRI) to improve the activation-detection performance over conventional approaches of fMRI analysis. In this method, first, ideal hemodynamic response time series for different stimuli were generated by convolving the theoretical hemodynamic response model with the stimulus timing. Second, constructing hypothetical signature vectors for different activity patterns of interest by virtue of the ideal hemodynamic responses, OLT was used to extract features of fMRI data. The resultant feature space had particular geometric clustering properties. It was then classified into different groups, each pertaining to an activity pattern of interest; the applied signature vector for each group was obtained by averaging. Third, using the applied signature vectors, OLT was applied again to generate fMRI composite images with high SNRs for the desired activity patterns. Simulations and a blocked fMRI experiment were employed for the method to be verified and compared with the general linear model (GLM)-based analysis. The simulation studies and the experimental results indicated the superiority of the proposed method over the GLM-based analysis in detecting brain activities.

Unattended emotional faces elicit early lateralized amygdala-frontal and fusiform activations.

Human adaptive behaviour to potential threats involves specialized brain responses allowing rapid and reflexive processing of the sensory input and a more directed processing for later evaluation of the nature of the threat. The amygdalae are known to play a key role in emotion processing. It is suggested that the amygdalae process threat-related information through a fast subcortical route and slower cortical feedback. Evidence from human data supporting this hypothesis is lacking. The present study investigated event-related neural responses during processing of facial emotions in the unattended hemifield using magnetoencephalography (MEG) and found activations of the amygdala and anterior cingulate cortex to fear as early as 100 ms. The right amygdala exhibited temporally dissociated activations to input from different visual fields, suggesting early subcortical versus later cortical processing of fear. We also observed asymmetrical fusiform activity related to lateralized feed-forward processing of the faces in the visual-ventral stream. Results demonstrate fast, automatic, and parallel processing of unattended emotional faces, providing important insights into the specific and dissociated neural pathways in emotion and face perception.