Neural underpinnings of threat bias in relation to loss-of-control eating behaviors among adolescent girls with high weight.

Introduction: Loss-of-control (LOC) eating, a key feature of binge-eating disorder, may relate attentional bias (AB) to highly salient interpersonal stimuli. The current pilot study used magnetoencephalography (MEG) to explore neural features of AB to socially threatening cues in adolescent girls with and without LOC-eating. Methods: Girls (12-17 years old) with overweight or obesity (BMI >85th percentile) completed an AB measure on an affective dot-probe AB task during MEG and evoked neural responses to angry or happy (vs. neutral) face cues were captured. A laboratory test meal paradigm measured energy intake and macronutrient consumption patterns. Results: Girls (N = 34; Mage = 15.5 ± 1.5 years; BMI-z = 1.7 ± 0.4) showed a blunted evoked response to the presentation of angry face compared with neutral face cues in the left dorsolateral prefrontal cortex, a neural region implicated in executive control and regulation processes, during attention deployment (p < 0.01). Compared with those without LOC-eating (N = 21), girls with LOC-eating (N = 13) demonstrated a stronger evoked response to angry faces in the visual cortex during attention deployment (p < 0.001). Visual and cognitive control ROIs had trends suggesting interaction with test meal intake patterns among girls with LOC-eating (ps = 0.01). Discussion: These findings suggest that girls with overweight or obesity may fail to adaptively engage neural regions implicated in higher-order executive processes. This difficulty may relate to disinhibited eating patterns that could lead to excess weight gain.

Spatiotemporal Alterations in Working Memory-Related Beta Band Neuromagnetic Activity of Patients With Schizophrenia On and Off Antipsychotic Medication: Investigation With MEG.

BACKGROUND AND HYPOTHESIS: We used the uniquely high combined spatial and temporal resolution of magnetoencephalography to characterize working memory (WM)-related modulation of beta band activity in neuroleptic-free patients with schizophrenia in comparison to a large sample of performance-matched healthy controls. We also tested for effects of antipsychotic medication on identified differences in these same patients. STUDY DESIGN: Inpatients with schizophrenia (n = 21) or psychotic disorder not otherwise specified (n = 4) completed N-back and control tasks during magnetoencephalography while on placebo and during antipsychotic medication treatment, in a blinded, randomized, counterbalanced manner. Healthy, performance-matched controls (N = 100) completed the same tasks. WM-related neural activation was estimated as beta band (14-30 Hz) desynchronization throughout the brain in successive 400 ms time windows. Voxel-wise statistical comparisons were performed between controls and patients while off-medication at each time window. Significant clusters resulting from this between-groups analysis were then used as regions-of-interest, the activations of which were compared between on- and off-medication conditions in patients. STUDY RESULTS: Controls showed beta-band desynchronization (activation) of a fronto-parietal network immediately preceding correct button press responses-the time associated with WM updating and task execution. Altered activation in medication-free patients occurred largely during this time, in prefrontal, parietal, and visual cortices. Medication altered patients' neural responses such that the activation time courses in these regions-of-interest more closely resembled those of controls. CONCLUSIONS: These findings demonstrate that WM-related beta band alterations in schizophrenia are time-specific and associated with neural systems targeted by antipsychotic medications. Future studies may investigate this association by examining its potential neurochemical basis.

Cross-Axis Dynamic Field Compensation of Optically Pumped Magnetometer Arrays for MEG.

We present dynamic field compensation (DFC), whereby three-axis field measurements from reference magnetometers are used to dynamically maintain null at the alkali vapor cells of an array of primary sensors that are proximal to a subject's scalp. Precision measurement of the magnetoencephalogram (MEG) by zero-field optically pumped magnetometer (OPM) sensors requires that sensor response is linear and sensor gain is constant over time. OPMs can be operated in open-loop mode, where the measured field is proportional to the output at the demodulated photodiode output, or in closed-loop, where on-board coils are dynamically driven to maintain the internal cell at zero field in the measurement direction. While OPMs can be operated in closed-loop mode along all three axes, this can increase sensor noise and poses engineering challenges. Uncompensated fluctuations in the ambient field along any statically nulled axes perturb the measured field by tipping the measurement axis and altering effective sensor gain - a phenomenon recently referred to as cross-axis projection error (CAPE). These errors are particularly problematic when OPMs are allowed to move in the remnant background field. Sensor gain-errors, if not mitigated, preclude precision measurements with OPMs operating in the presence of ambient field fluctuations within a typical MEG laboratory. In this manuscript, we present the cross-axis dynamic field compensation (DFC) method for maintaining zero field dynamically on all three axes of each sensor in an array of OPMs. Together, DFC and closed-loop operation strongly attenuate errors introduced by CAPE. This method was implemented by using three orthogonal reference sensors together with OPM electronics that permit driving each sensor's transverse field coils dynamically to maintain null field across its OPM measurement cell. These reference sensors can also be used for synthesizing 1st-gradient response to further reduce the effects of fluctuating ambient fields on measured brain activity and compensate for movement within a uniform field. We demonstrate that, using the DFC method, magnetic field measurement errors of less than 0.7% are easily achieved for an array of OPM sensors in the presence of ambient field perturbations of several nT.

On-scalp magnetocorticography with optically pumped magnetometers: Simulated performance in resolving simultaneous sources.

Currently, the gold standard for high-resolution mapping of cortical electrophysiological activity is invasive electrocorticography (ECoG), a procedure that carries with it the risk of serious morbidity and mortality. Due to these risks, the use of ECoG is largely limited to pre-surgical mapping in intractable epilepsy. Nevertheless, many seminal studies in neuroscience have utilized ECoG to explore domains such as visual perception, attention, auditory processing, and sensorimotor behavior. Studies such as these, occurring in patients with epilepsy rather than healthy controls, may lack generalizability, and are limited by the placement of the electrode arrays over the presumed seizure focus. This manuscript explores the use of optically pumped magnetometers (OPMs) to create a non-invasive alternative to ECoG, which we refer to as magnetocorticography. Because prior ECoG studies reveal that most cognitive processes are driven by multiple, simultaneous independent neuronal assemblies, we characterize the ability of a theoretical 56-channel dense OPM array to resolve simultaneous independent sources, and compare it to currently available SQUID devices, as well as OPM arrays with inter-sensor spacings more typical of other systems in development. Our evaluation of this theoretical system assesses many potential sources of error, including errors of sensor calibration and position. In addition, we investigate the influence of geometrical and anatomical factors on array performance. Our simulations reveal the potential of high-density, on-scalp OPM MEG devices to localize electrophysiological brain responses at unprecedented resolution for a non-invasive device.

A dual role of prestimulus spontaneous neural activity in visual object recognition.

Vision relies on both specific knowledge of visual attributes, such as object categories, and general brain states, such as those reflecting arousal. We hypothesized that these phenomena independently influence recognition of forthcoming stimuli through distinct processes reflected in spontaneous neural activity. Here, we recorded magnetoencephalographic (MEG) activity in participants (N = 24) who viewed images of objects presented at recognition threshold. Using multivariate analysis applied to sensor-level activity patterns recorded before stimulus presentation, we identified two neural processes influencing subsequent subjective recognition: a general process, which disregards stimulus category and correlates with pupil size, and a specific process, which facilitates category-specific recognition. The two processes are doubly-dissociable: the general process correlates with changes in criterion but not in sensitivity, whereas the specific process correlates with changes in sensitivity but not in criterion. Our findings reveal distinct mechanisms of how spontaneous neural activity influences perception and provide a framework to integrate previous findings.

Prefrontal high gamma during a magnetoencephalographic working memory task.

In human electrophysiology research, the high gamma part of the power spectrum (~>60 Hz) is a relatively new area of investigation. Despite a low signal-to-noise ratio, evidence exists that it contains significant information about activity in local cortical networks. Here, using magnetoencephalography (MEG), we found high gamma activity when comparing data from an n-back working memory task to resting data in a large sample of normal volunteers. Initial analysis of power spectra from 0-back, 2-back, and rest trials showed three frequency bands exhibiting task-related differences: alpha, beta, and high gamma. Unlike alpha and beta, the high gamma spectrum was broad, without a peak at a single frequency. In addition, power in high gamma was highest for the 2-back and lowest during rest, while the opposite pattern occurred in the other bands. Beamformer source localization of each of the three frequency bands revealed a distinct set of sources for high gamma. These included several regions of prefrontal cortex that exhibited greater power when both n-back conditions were compared to rest. A subset of these regions had more power when the 2-back was compared to 0-back, which indicates a role in working memory performance. Our results show that high gamma will be important for understanding cortical processing during cognitive and other tasks. Furthermore, data from human intracortical recordings suggest that high gamma is the aggregate of spiking in local cortical networks, which implies that MEG could serve to bridge experimental modalities by noninvasively observing task-related modulation of spiking rates.

Neural Integration of Stimulus History Underlies Prediction for Naturalistically Evolving Sequences.

Forming valid predictions about the environment is crucial to survival. However, whether humans are able to form valid predictions about natural stimuli based on their temporal statistical regularities remains unknown. Here, we presented subjects with tone sequences with pitch fluctuations that, over time, capture long-range temporal dependence structures prevalent in natural stimuli. We found that subjects were able to exploit such naturalistic statistical regularities to make valid predictions about upcoming items in a sequence. Magnetoencephalography (MEG) recordings revealed that slow, arrhythmic cortical dynamics tracked the evolving pitch sequence over time such that neural activity at a given moment was influenced by the pitch of up to seven previous tones. Importantly, such history integration contained in neural activity predicted the expected pitch of the upcoming tone, providing a concrete computational mechanism for prediction. These results establish humans' ability to make valid predictions based on temporal regularities inherent in naturalistic stimuli and further reveal the neural mechanisms underlying such predictive computation.SIGNIFICANCE STATEMENT A fundamental question in neuroscience is how the brain predicts upcoming events in the environment. To date, this question has primarily been addressed in experiments using relatively simple stimulus sequences. Here, we studied predictive processing in the human brain using auditory tone sequences that exhibit temporal statistical regularities similar to those found in natural stimuli. We observed that humans are able to form valid predictions based on such complex temporal statistical regularities. We further show that neural response to a given tone in the sequence reflects integration over the preceding tone sequence and that this history dependence forms the foundation for prediction. These findings deepen our understanding of how humans form predictions in an ecologically valid environment.

Heightened amygdala responsiveness in s-carriers of 5-HTTLPR genetic polymorphism reflects enhanced cortical rather than subcortical inputs: An MEG study.

Short allele carriers (S-carriers) of the serotonin transporter gene (5-HTTLPR) show an elevated amygdala response to emotional stimuli relative to long allele carriers (LL-homozygous). However, whether this reflects increased responsiveness of the amygdala generally or interactions between the amygdala and the specific input systems remains unknown. It is argued that the amygdala receives input via a quick subcortical and a slower cortical pathway. If the elevated amygdala response in S-carriers reflects generally increased amygdala responding, then group differences in amygdala should be seen across the amygdala response time course. However, if the difference is a secondary consequence of enhanced amygdala-cortical interactions, then group differences might only be present later in the amygdala response. Using magnetoencephalography (MEG), we found an enhanced amygdala response to fearful expressions starting 40-50 ms poststimulus. However, group differences in the amygdala were only seen 190-200 ms poststimulus, preceded by increased superior temporal sulcus (STS) responses in S-carriers from 130 to 140 ms poststimulus. An enhanced amygdala response to angry expressions started 260-270 ms poststimulus with group differences in the amygdala starting at 160-170 ms poststimulus onset, preceded by increased STS responses in S-carriers from 150 to 160 ms poststimulus. These suggest that enhanced amygdala responses in S-carriers might reflect enhanced STS-amygdala connectivity in S-carriers. Hum Brain Mapp 38:4313-4321, 2017. © 2017 Wiley Periodicals, Inc.

Threat of shock increases excitability and connectivity of the intraparietal sulcus.

Anxiety disorders affect approximately 1 in 5 (18%) Americans within a given 1 year period, placing a substantial burden on the national health care system. Therefore, there is a critical need to understand the neural mechanisms mediating anxiety symptoms. We used unbiased, multimodal, data-driven, whole-brain measures of neural activity (magnetoencephalography) and connectivity (fMRI) to identify the regions of the brain that contribute most prominently to sustained anxiety. We report that a single brain region, the intraparietal sulcus (IPS), shows both elevated neural activity and global brain connectivity during threat. The IPS plays a key role in attention orienting and may contribute to the hypervigilance that is a common symptom of pathological anxiety. Hyperactivation of this region during elevated state anxiety may account for the paradoxical facilitation of performance on tasks that require an external focus of attention, and impairment of performance on tasks that require an internal focus of attention.

Localization of Interictal Epileptic Spikes With MEG: Optimization of an Automated Beamformer Screening Method (SAMepi) in a Diverse Epilepsy Population.

PURPOSE: To describe and optimize an automated beamforming technique followed by identification of locations with excess kurtosis (g2) for efficient detection and localization of interictal spikes in patients with medically refractory epilepsy. METHODS: Synthetic aperture magnetometry with g2 averaged over a sliding time window (SAMepi) was performed in seven patients with focal epilepsy and five healthy volunteers. The effect of varied window lengths on detection of spiking activity was evaluated. RESULTS: Sliding window lengths of 0.5 to 10 seconds performed similarly, with 0.5- and 1-second windows detecting spiking activity in 1 of the 3 virtual sensor locations with highest kurtosis. These locations were concordant with the region of eventual surgical resection in these seven patients who remained seizure-free at 1 year. Average g2 values increased with increasing sliding window length in all subjects. In healthy volunteers, kurtosis values stabilized in data sets longer than 2 minutes. CONCLUSIONS: SAMepi using g2 averaged over 1-second sliding time windows in data sets of at least 2 minutes of duration reliably identified interictal spiking and the presumed seizure focus in these seven patients. Screening the five locations with highest kurtosis values for spiking activity is an efficient and accurate technique for localizing interictal activity using magnetoencephalography. SIGNIFICANCE: SAMepi should be applied using the parameter values and procedure described for optimal detection and localization of interictal spikes. Use of this screening procedure could significantly improve the efficiency of magnetoencephalography analysis if clinically validated.

Detecting Functional Connectivity During Audiovisual Integration with MEG: A Comparison of Connectivity Metrics.

In typical magnetoencephalography and/or electroencephalography functional connectivity analysis, researchers select one of several methods that measure a relationship between regions to determine connectivity, such as coherence, power correlations, and others. However, it is largely unknown if some are more suited than others for various types of investigations. In this study, the authors investigate seven connectivity metrics to evaluate which, if any, are sensitive to audiovisual integration by contrasting connectivity when tracking an audiovisual object versus connectivity when tracking a visual object uncorrelated with the auditory stimulus. The authors are able to assess the metrics' performances at detecting audiovisual integration by investigating connectivity between auditory and visual areas. Critically, the authors perform their investigation on a whole-cortex all-to-all mapping, avoiding confounds introduced in seed selection. The authors find that amplitude-based connectivity measures in the beta band detect strong connections between visual and auditory areas during audiovisual integration, specifically between V4/V5 and auditory cortices in the right hemisphere. Conversely, phase-based connectivity measures in the beta band as well as phase and power measures in alpha, gamma, and theta do not show connectivity between audiovisual areas. The authors postulate that while beta power correlations detect audiovisual integration in the current experimental context, it may not always be the best measure to detect connectivity. Instead, it is likely that the brain utilizes a variety of mechanisms in neuronal communication that may produce differential types of temporal relationships.

Convergent BOLD and Beta-Band Activity in Superior Temporal Sulcus and Frontolimbic Circuitry Underpins Human Emotion Cognition.

The processing of social information in the human brain is widely distributed neuroanatomically and finely orchestrated over time. However, a detailed account of the spatiotemporal organization of these key neural underpinnings of human social cognition remains to be elucidated. Here, we applied functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in the same participants to investigate spatial and temporal neural patterns evoked by viewing videos of facial muscle configurations. We show that observing the emergence of expressions elicits sustained blood oxygenation level-dependent responses in the superior temporal sulcus (STS), a region implicated in processing meaningful biological motion. We also found corresponding event-related changes in sustained MEG beta-band (14-30 Hz) oscillatory activity in the STS, consistent with the possible role of beta-band activity in visual perception. Dynamically evolving fearful and happy expressions elicited early (0-400 ms) transient beta-band activity in sensorimotor cortex that persisted beyond 400 ms, at which time it became accompanied by a frontolimbic spread (400-1000 ms). In addition, individual differences in sustained STS beta-band activity correlated with speed of emotion recognition, substantiating the behavioral relevance of these signals. This STS beta-band activity showed valence-specific coupling with the time courses of facial movements as they emerged into full-blown fearful and happy expressions (negative and positive coupling, respectively). These data offer new insights into the perceptual relevance and orchestrated function of the STS and interconnected pathways in social-emotion cognition.

Graph theoretical analysis of resting magnetoencephalographic functional connectivity networks.

Complex networks have been observed to comprise small-world properties, believed to represent an optimal organization of local specialization and global integration of information processing at reduced wiring cost. Here, we applied magnitude squared coherence to resting magnetoencephalographic time series in reconstructed source space, acquired from controls and patients with schizophrenia, and generated frequency-dependent adjacency matrices modeling functional connectivity between virtual channels. After configuring undirected binary and weighted graphs, we found that all human networks demonstrated highly localized clustering and short characteristic path lengths. The most conservatively thresholded networks showed efficient wiring, with topographical distance between connected vertices amounting to one-third as observed in surrogate randomized topologies. Nodal degrees of the human networks conformed to a heavy-tailed exponentially truncated power-law, compatible with the existence of hubs, which included theta and alpha bilateral cerebellar tonsil, beta and gamma bilateral posterior cingulate, and bilateral thalamus across all frequencies. We conclude that all networks showed small-worldness, minimal physical connection distance, and skewed degree distributions characteristic of physically-embedded networks, and that these calculations derived from graph theoretical mathematics did not quantifiably distinguish between subject populations, independent of bandwidth. However, post-hoc measurements of edge computations at the scale of the individual vertex revealed trends of reduced gamma connectivity across the posterior medial parietal cortex in patients, an observation consistent with our prior resting activation study that found significant reduction of synthetic aperture magnetometry gamma power across similar regions. The basis of these small differences remains unclear.

Neuronal avalanches in the resting MEG of the human brain.

What constitutes normal cortical dynamics in healthy human subjects is a major question in systems neuroscience. Numerous in vitro and in vivo animal studies have shown that ongoing or resting cortical dynamics are characterized by cascades of activity across many spatial scales, termed neuronal avalanches. In experiment and theory, avalanche dynamics are identified by two measures: (1) a power law in the size distribution of activity cascades with an exponent of -3/2 and (2) a branching parameter of the critical value of 1, reflecting balanced propagation of activity at the border of premature termination and potential blowup. Here we analyzed resting-state brain activity recorded using noninvasive magnetoencephalography (MEG) from 124 healthy human subjects and two different MEG facilities using different sensor technologies. We identified large deflections at single MEG sensors and combined them into spatiotemporal cascades on the sensor array using multiple timescales. Cascade size distributions obeyed power laws. For the timescale at which the branching parameter was close to 1, the power law exponent was -3/2. This relationship was robust to scaling and coarse graining of the sensor array. It was absent in phase-shuffled controls with the same power spectrum or empty scanner data. Our results demonstrate that normal cortical activity in healthy human subjects at rest organizes as neuronal avalanches and is well described by a critical branching process. Theory and experiment have shown that such critical, scale-free dynamics optimize information processing. Therefore, our findings imply that the human brain attains an optimal dynamical regime for information processing.

Theta band activity in response to emotional expressions and its relationship with gamma band activity as revealed by MEG and advanced beamformer source imaging.

Neuronal oscillations in the theta and gamma bands have been shown to be important for cognition. Here we examined the temporal and spatial relationship between the two frequency bands in emotional processing using magnetoencephalography and an advanced dynamic beamformer source imaging method called synthetic aperture magnetometry. We found that areas including the amygdala, visual and frontal cortex showed significant event-related synchronization in both bands, suggesting a functional association of neuronal oscillations in the same areas in the two bands. However, while the temporal profile in both bands was similar in the amygdala, the peak in gamma band power was much earlier within both visual and frontal areas. Our results do not support a traditional view that the localizations of lower and higher frequencies are spatially distinct. Instead, they suggest that in emotional processing, neuronal oscillations in the gamma and theta bands may reflect, at least in visual and frontal cortex either different but related functional processes or, perhaps more probably, different computational components of the same functional process.

Isolating neural components of threat bias in pediatric anxiety.

BACKGROUND: Attention biases toward threat are often detected in individuals with anxiety disorders. Threat biases can be measured experimentally through dot-probe paradigms, in which individuals detect a probe following a stimulus pair including a threat. On these tasks, individuals with anxiety tend to detect probes that occur in a location previously occupied by a threat (i.e., congruent) faster than when opposite threats (i.e., incongruent). In pediatric anxiety disorders, dot-probe paradigms detect abnormal attention biases toward threat and abnormal ventrolateral prefrontal cortex (vlPFC) function. However, it remains unclear if this aberrant vlPFC activation occurs while subjects process threats (e.g., angry faces) or, alternatively, while they process and respond to probes. This magnetoencephalography (MEG) study was designed to answer this question. METHODS: Adolescents with either generalized anxiety disorder (GAD, n = 17) or no psychiatric diagnosis (n = 25) performed a dot-probe task involving angry and neutral faces while MEG data were collected. Synthetic Aperture Magnetometry (SAM) beamformer technique was used to determine whether there were group differences in power ratios while subjects processed threats (i.e., angry vs. neutral faces) or when subjects responded to incongruent versus. congruent probes. RESULTS: Group differences in vlPFC activation during the response period emerged with a 1-30 Hz frequency band. No group differences in vlPFC activation were detected in response to angry-face cues. CONCLUSIONS: In the dot-probe task, anxiety-related perturbations in vlPFC activation reflect abnormal attention control when responding to behaviorally relevant probes, but not to angry faces. Given that motor responses to these probes are used to calculate threat bias, this study provides insight into the pathophysiology reflected in this commonly used marker of anxiety. In addition, this finding may inform the development of novel anxiety-disorder treatments targeting the vlPFC to enhance attention control to task-relevant demands.

Functional Brain Network Characterization and Adaptivity during Task Practice in Healthy Volunteers and People with Schizophrenia.

Cognitive remediation involves task practice and may improve deficits in people suffering from schizophrenia, but little is known about underlying neurophysiological mechanisms. In people with schizophrenia and controls, we used magnetoencephalography (MEG) to examine accuracy and practice-related changes in parameters indexing neural network structure and activity, to determine whether these might be useful assays of the efficacy of cognitive remediation. Two MEG recordings were acquired during performance of a tone discrimination task used to improve the acuity of auditory processing, before and after ∼2.5 h of task practice. Accuracy before practice was negatively correlated with beta-band cost efficiency, a graph theoretical measure of network organization. Synthetic aperture magnetometry was used to localize brain oscillations with high spatial accuracy; results demonstrated sound and sensorimotor modulations of the beta band in temporo-parietal regions and the sensorimotor cortex respectively. High-gamma activity also correlated with sensorimotor processing during the task, with activation of auditory regions following sound stimulation, and activation of the left sensorimotor cortex preceding the button press. High-gamma power in the left frontal cortex was also found to correlate with accuracy. Following practice, sound-induced broad-band power in the left angular gyri increased. Accuracy improved and was found to correlate with increased mutual information (MI) between sensors in temporal-parietal regions in the beta band but not global cost efficiency. Based on these results, we conclude that hours of task practice can induce meso-scale changes such as increased power in relevant brain regions as well as changes in MI that correlate with improved accuracy.

Task-specific modulation of human auditory evoked response in a delayed-match-to-sample task.

In this study, we focus our investigation on task-specific cognitive modulation of early cortical auditory processing in human cerebral cortex. During the experiments, we acquired whole-head magnetoencephalography data while participants were performing an auditory delayed-match-to-sample (DMS) task and associated control tasks. Using a spatial filtering beamformer technique to simultaneously estimate multiple source activities inside the human brain, we observed a significant DMS-specific suppression of the auditory evoked response to the second stimulus in a sound pair, with the center of the effect being located in the vicinity of the left auditory cortex. For the right auditory cortex, a non-invariant suppression effect was observed in both DMS and control tasks. Furthermore, analysis of coherence revealed a beta band (12∼20 Hz) DMS-specific enhanced functional interaction between the sources in left auditory cortex and those in left inferior frontal gyrus, which has been shown to be involved in short-term memory processing during the delay period of DMS task. Our findings support the view that early evoked cortical responses to incoming acoustic stimuli can be modulated by task-specific cognitive functions by means of frontal-temporal functional interactions.

Different neural pathways to negative affect in youth with pediatric bipolar disorder and severe mood dysregulation.

Questions persist regarding the presentation of bipolar disorder (BD) in youth and the nosological significance of irritability. Of particular interest is whether severe mood dysregulation (SMD), characterized by severe non-episodic irritability, hyper-arousal, and hyper-reactivity to negative emotional stimuli, is a developmental presentation of pediatric BD and, therefore, whether the two conditions are pathophysiologically similar. We administered the affective Posner paradigm, an attentional task with a condition involving blocked goal attainment via rigged feedback. The sample included 60 youth (20 BD, 20 SMD, and 20 controls) ages 8-17. Magnetoencephalography (MEG) examined neuronal activity (4-50 Hz) following negative versus positive feedback. We also examined reaction time (RT), response accuracy, and self-reported affect. Both BD and SMD youth reported being less happy than controls during the rigged condition. Also, SMD youth reported greater arousal following negative feedback than both BD and controls, and they responded to negative feedback with significantly greater activation of the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG) than controls. Compared to SMD and controls, BD youth displayed greater superior frontal gyrus (SFG) activation and decreased insula activation following negative feedback. Data suggest a greater negative affective response to blocked goal attainment in SMD versus BD and control youth. This occurs in tandem with hyperactivation of medial frontal regions in SMD youth, while BD youth show dysfunction in the SFG and insula. Data add to a growing empirical base that differentiates pediatric BD and SMD and begin to elucidate potential neural mechanisms of irritability.

Neuromagnetic measures of word processing in bilinguals and monolinguals.

OBJECTIVE: This study aimed to use magnetoencephalography (MEG) to examine the question of whether Mandarin-English bilingual speakers recruit the same cortical areas or develop distinct language-specific networks without overlaps for word processing. METHODS: Eight healthy Mandarin-English bilingual adults and eight healthy English monolingual adults were scanned while single-word paradigms were audio-visually presented. RESULTS: Our results showed significantly stronger beta-band power suppression in the right inferior parietal lobe (IPL) covering the supramarginal gyrus (BA 40) and angular gyrus (BA 39) for bilinguals when processing Mandarin versus English. Moreover, there were no significant differences between bilinguals and monolinguals in the left inferior frontal cortex (LIFC, BA 44/45) when both were processing their first language. CONCLUSIONS: These results support the view that Mandarin-English bilinguals have a shared neural system for word processing in both the first and second language, which is highly similar to monolinguals', but with stronger right hemisphere involvement. SIGNIFICANCE: To our knowledge, this is the first MEG study to investigate the spatio-temporal and frequency characteristics between bilinguals and monolinguals, which provides us a new angle to better understand the language system in bilinguals' and monolingual's brain.