Investigating default mode network connectivity disruption in children of mothers with depression.

BACKGROUND: Exposure to maternal major depressive disorder (MDD) bears long-term negative consequences for children's well-being; to date, no research has examined how exposure at different stages of development differentially affects brain functioning. AIMS: Utilising a unique cohort followed from birth to preadolescence, we examined the effects of early versus later maternal MDD on default mode network (DMN) connectivity. METHOD: Maternal depression was assessed at birth and ages 6 months, 9 months, 6 years and 10 years, to form three groups: children of mothers with consistent depression from birth to 6 years of age, which resolved by 10 years of age; children of mothers without depression; and children of mothers who were diagnosed with MDD in late childhood. In preadolescence, we used magnetoencephalography and focused on theta rhythms, which characterise the developing brain. RESULTS: Maternal MDD was associated with disrupted DMN connectivity in an exposure-specific manner. Early maternal MDD decreased child connectivity, presenting a profile typical of early trauma or chronic adversity. In contrast, later maternal MDD was linked with tighter connectivity, a pattern characteristic of adult depression. Aberrant DMN connectivity was predicted by intrusive mothering in infancy and lower mother-child reciprocity and child empathy in late childhood, highlighting the role of deficient caregiving and compromised socio-emotional competencies in DMN dysfunction. CONCLUSIONS: The findings pinpoint the distinct effects of early versus later maternal MDD on the DMN, a core network sustaining self-related processes. Results emphasise that research on the influence of early adversity on the developing brain should consider the developmental stage in which the adversity occured.

Brain responses to other people's pain in fibromyalgia: a magnetoencephalography study.

OBJECTIVES: We investigated whether the central pain symptoms in fibromyalgia syndrome (FM) are related to defective top-down sensorimotor regulation. The pain matrix was activated in a top-down manner by presenting pictures of painful situations while recording brain activity using magnetoencephalography (MEG). We investigated alpha desynchronisation in FM patients and healthy controls in response to pictures depicting pain. METHODS: 19 FM patients and 14 age-matched healthy controls (age 20-60) were recruited. Participants were shown photographs of right hands and feet in situations depicting pain or of control situations with no depiction of pain. MEG was recorded in a whole-head 248-sensor system as subjects laid supine. RESULTS: In healthy controls exposure to pictures depicting painful situations elicited a decrease in alpha activity (10Hz) at 100-500ms post-stimulus, which was significantly more pronounced than the one elicited by non-painful content mostly on sensors above the right sensorimotor cortex. However, FM patients did not show significant differences in alpha activity between responses to pain and no-pain pictures. CONCLUSIONS: Consistent with previous findings, healthy participants displayed stronger alpha desynchronisation for pain pictures, indicating automatic disinhibition of the sensorimotor cortices in response to the observation of pain in others. We found evidence for a deficient modulation of sensorimotor cortex in FM patients. The lack of differential response suggests that they perceived relatively neutral pictures as potentially painful, at least in this setting. Our findings suggest that defective top-down regulation may play a role in the pathogenesis of FM.

Adolescents growing up amidst intractable conflict attenuate brain response to pain of outgroup.

Adolescents' participation in intergroup conflicts comprises an imminent global risk, and understanding its neural underpinnings may open new perspectives. We assessed Jewish-Israeli and Arab-Palestinian adolescents for brain response to the pain of ingroup/outgroup protagonists using magnetoencephalography (MEG), one-on-one positive and conflictual interactions with an outgroup member, attitudes toward the regional conflict, and oxytocin levels. A neural marker of ingroup bias emerged, expressed via alpha modulations in the somatosensory cortex (S1) that characterized an automatic response to the pain of all protagonists followed by rebound/enhancement to ingroup pain only. Adolescents' hostile social interactions with outgroup members and uncompromising attitudes toward the conflict influenced this neural marker. Furthermore, higher oxytocin levels in the Jewish-Israeli majority and tighter brain-to-brain synchrony among group members in the Arab-Palestinian minority enhanced the neural ingroup bias. Findings suggest that in cases of intractable intergroup conflict, top-down control mechanisms may block the brain's evolutionary-ancient resonance to outgroup pain, pinpointing adolescents' interpersonal and sociocognitive processes as potential targets for intervention.

Deviations from Critical Dynamics in Interictal Epileptiform Activity.

The framework of criticality provides a unifying perspective on neuronal dynamics from in vitro cortical cultures to functioning human brains. Recent findings suggest that a healthy cortex displays critical dynamics, giving rise to scale-free spatiotemporal cascades of activity, termed neuronal avalanches. Pharmacological manipulations of the excitation-inhibition balance (EIB) in cortical cultures were previously shown to result in deviations from criticality and from the power law scaling of avalanche size distribution. To examine the sensitivity of neuronal avalanche metrics to altered EIB in humans, we focused on epilepsy, a neurological disorder characterized by hyperexcitable networks. Using magnetoencephalography, we quantitatively assessed deviations from criticality in the brain dynamics of patients with epilepsy during interictal (between-seizures) activity. Compared with healthy control subjects, epilepsy patients tended to exhibit a higher neural gain and larger avalanches, particularly during interictal epileptiform activity. Moreover, deviations from scale-free behavior were exclusively connected to brief intervals at epileptiform discharges, strengthening the association between deviations from criticality and the instantaneous changes in EIB. The avalanches collected during interictal epileptiform activity had not only a stereotypical size range but also involved particular spatial patterns of activations, as expected for periods of epileptic network dominance. Overall, the neuronal avalanche metrics provide a quantitative novel description of interictal brain activity of patients with epilepsy. SIGNIFICANCE STATEMENT: Healthy brain dynamics requires a delicate balance between excitatory and inhibitory processes. Several brain disorders, such as epilepsy, are associated with altered excitation-inhibition balance, but assessing this balance using noninvasive tools is still challenging. In this study, we apply the framework of critical brain dynamics to data from epilepsy patients, which were recorded between seizures. We show that metrics of criticality provide a sensitive tool for noninvasive assessment of changes in the balance. Specifically, brain activity of epilepsy patients deviates from healthy critical brain dynamics, particularly during abnormal epileptiform activity. The study offers a novel quantitative perspective on epilepsy and its relation to healthy brain dynamics.

Impairment in predictive processes during auditory mismatch negativity in ScZ: Evidence from event-related fields.

Patients with schizophrenia (ScZ) show pronounced dysfunctions in auditory perception but the underlying mechanisms as well as the localization of the deficit remain unclear. To examine these questions, the current study examined whether alterations in the neuromagnetic mismatch negativity (MMNm) in ScZ-patients could involve an impairment in sensory predictions in local sensory and higher auditory areas. Using a whole-head MEG-approach, we investigated the MMNm as well as P300m and N100m amplitudes during a hierarchical auditory novelty paradigm in 16 medicated ScZ-patients and 16 controls. In addition, responses to omitted sounds were investigated, allowing for a critical test of the predictive coding hypothesis. Source-localization was performed to identify the generators of the MMNm, omission responses as well as the P300m. Clinical symptoms were examined with the positive and negative syndrome scale. Event-related fields (ERFs) to standard sounds were intact in ScZ-patients. However, the ScZ-group showed a reduction in the amplitude of the MMNm during both local (within trials) and global (across trials) conditions as well as an absent P300m at the global level. Importantly, responses to sound omissions were reduced in ScZ-patients which overlapped both in latency and generators with the MMNm sources. Thus, our data suggest that auditory dysfunctions in ScZ involve impaired predictive processes that involve deficits in both automatic and conscious detection of auditory regularities. Hum Brain Mapp 38:5082-5093, 2017. © 2017 Wiley Periodicals, Inc.

Selective Neural Synchrony Suppression as a Forward Gatekeeper to Piecemeal Conscious Perception.

The emergence of conscious visual perception is assumed to ignite late (∼250 ms) gamma-band oscillations shortly after an initial (∼100 ms) forward sweep of neural sensory (nonconscious) information. However, this neural evidence is not utterly congruent with rich behavioral data which rather point to piecemeal (i.e., graded) perceptual processing. To address the unexplored neural mechanisms of piecemeal ignition of conscious perception, hierarchical script sensitivity of the putative visual word form area (VWFA) was exploited to signal null (i.e., sensory), partial (i.e., letter-level), and full (i.e., word-level) conscious perception. Two magnetoencephalography experiments were conducted in which healthy human participants viewed masked words (Experiment I: active task, Dutch words; Experiment II: passive task, Hebrew words) while high-frequency (broadband gamma) brain activity was measured. Findings revealed that piecemeal conscious perception did not ignite a linear piecemeal increase in oscillations. Instead, whereas late (∼250 ms) gamma-band oscillations signaled full conscious perception (i.e., word-level), partial conscious perception (i.e., letter-level) was signaled via the inhibition of the early (∼100 ms) forward sweep. This inhibition regulates the downstream broadcast to filter out irrelevant (i.e., masks) information. The findings thus highlight a local (VWFA) gatekeeping mechanism for conscious perception, operating by filtering out and in selective percepts.

Near-Critical Dynamics in Stimulus-Evoked Activity of the Human Brain and Its Relation to Spontaneous Resting-State Activity.

In recent years, numerous studies have found that the brain at resting state displays many features characteristic of a critical state. Here we examine whether stimulus-evoked activity can also be regarded as critical. Additionally, we investigate the relation between resting-state activity and stimulus-evoked activity from the perspective of criticality. We found that cortical activity measured by magnetoencephalography (MEG) is near critical and organizes as neuronal avalanches at both resting-state and stimulus-evoked activities. Moreover, a significantly high intrasubject similarity between avalanche size and duration distributions at both cognitive states was found, suggesting that the distributions capture specific features of the individual brain dynamics. When comparing different subjects, a higher intersubject consistency was found for stimulus-evoked activity than for resting state. This was expressed by the distance between avalanche size and duration distributions of different participants and was supported by the spatial spreading of the avalanches involved. During the course of stimulus-evoked activity, time locked to the stimulus onset, we demonstrate fluctuations in the gain of the neuronal system and thus short timescale deviations from the critical state. Nonetheless, the overall near-critical state in stimulus-evoked activity is retained over longer timescales, in close proximity and with a high correlation to spontaneous (not time-locked) resting-state activity. Spatially, the observed fluctuations in gain manifest through anticorrelative activations of brain sites involved, suggesting a switch between task-negative (default mode) and task-positive networks and assigning the changes in excitation-inhibition balance to nodes within these networks. Overall, this study offers a novel outlook on evoked activity through the framework of criticality. SIGNIFICANCE STATEMENT: The organization of stimulus-evoked activity and ongoing cortical activity is a topic of high importance. The article addresses several general questions. What is the spatiotemporal organization of stimulus-evoked cortical activity in healthy human subjects? Are there deviations from excitation-inhibition balance during stimulus-evoked activity? What is the relationship between stimulus-evoked activity and ongoing resting-state activity? Using magnetoencephalography (MEG), we demonstrate that stimulus-evoked activity in humans follows a critical branching process that produces neuronal avalanches. Additionally, we investigate the spatiotemporal relationship between resting-state activity and stimulus-evoked activity from the perspective of critical dynamics. These analyses reveal new aspects of this complex relationship and offer novel insights into the interplay between excitation and inhibition that were not observed previously using conventional approaches.

Oxytocin selectively modulates brain response to stimuli probing social synchrony.

The capacity to act collectively within groups has led to the survival and thriving of Homo sapiens. A central group collaboration mechanism is "social synchrony," the coordination of behavior during joint action among affiliative members, which intensifies under threat. Here, we tested brain response to vignettes depicting social synchrony among combat veterans trained for coordinated action and following life-threatening group experience, versus controls, as modulated by oxytocin (OT), a neuropeptide supporting social synchrony. Using a randomized, double-blind, within-subject design, 40 combat-trained and control male veterans underwent magnetoencephalography (MEG) twice following OT/placebo administration while viewing two social vignettes rated as highly synchronous: pleasant male social gathering and coordinated unit during combat. Both vignettes activated a wide response across the social brain in the alpha band; the combat scene triggered stronger activations. Importantly, OT effects were modulated by prior experience. Among combat veterans, OT attenuated the increased response to combat stimuli in the posterior superior temporal sulcus (pSTS) - a hub of social perception, action observation, and mentalizing - and enhanced activation in the inferior parietal lobule (IPL) to the pleasant social scene. Among controls, OT enhanced inferior frontal gyrus (IFG) response to combat cues, demonstrating selective OT effects on mirror-neuron and mentalizing networks. OT-enhanced mirror network activity was dampened in veterans reporting higher posttraumatic symptoms. Results demonstrate that the social brain responds online, via modulation of alpha rhythms, to stimuli probing social synchrony, particularly those involving threat to survival, and OT's enhancing versus anxiolytic effects are sensitive to salient experiences within social groups.

Prior exposure to extreme pain alters neural response to pain in others.

In the extant literature examining the brain mechanisms implicated in pain perception, researchers have theorized that the overlapping responses to pain in the self and in others mark the human capacity for empathy. Here we investigated how prior exposure to extreme pain affects pain perception, by assessing the dynamics of pain processing in veterans who were previously exposed to severe injury. Forty-three participants (28 pain-exposed and 15 controls) underwent whole-head magnetoencephalography (MEG) while viewing photographs of limbs in painful and nonpainful (neutral) conditions. Among controls, an early (0-220 ms) "pain effect" in the posterior cingulate and sensorimotor cortices, and a later (760-900 ms) "pain effect" in the posterior cingulate cortex, superior temporal gyrus/insula, and fusiform gyrus were found, indicated by enhanced alpha suppression to the pain versus nonpain conditions. Importantly, pain-exposed participants exhibited an atypical pain response in the posterior cingulate cortex, indicated by a normative response to pain, but no pain-to-no-pain differentiation. This may suggest that individuals exposed to extreme pain may perceive neutral stimuli as potentially threatening. Our findings demonstrate alterations in pain perception following extreme pain exposure, chart the sequence from automatic to evaluative pain processing, and emphasize the importance of considering past experiences in studying the neural response to others' states.

Right semantic modulation of early MEG components during ambiguity resolution.

The time-line of lexical ambiguity resolution in bilateral neuronal networks was investigated using magnetoencephalography (MEG) in a semantic decision task. Dominant and subordinate associations of ambiguous words are considered to be processed in the left and right hemispheres, respectively. In the experiment, ambiguous words were followed by dominant or subordinate associations (manipulated between blocks) or by unrelated target words, and participants (N=25) decided whether the words in each pair were related or not. Subordinate meaning blocks elicited greater changes in the magnetic fields relative to dominant ones over the right, but not the left hemisphere (LH) at 150-235 ms from target onset, a time window corresponding to the M/N170 M/EEG component. Beamforming analysis localized the differential right hemisphere (RH) activity at the perisylvian area, including the homologue regions of Broca's and Wernicke's. At a later stage (235-390 ms) there was no significant difference between the two meaning conditions. We suggest that the RH language regions assist the LH in integrating subordinate disambiguating clues to preceding context during the M170 time window.

A magnetoencephalographic study of face processing: M170, gamma-band oscillations and source localization.

EEG studies suggested that the N170 ERP and Gamma-band responses to faces reflect early and later stages of a multiple-level face-perception mechanism, respectively. However, these conclusions should be considered cautiously because EEG-recorded Gamma may be contaminated by noncephalic activity such as microsaccades. Moreover, EEG studies of Gamma cannot easily reveal its intracranial sources. Here we recorded MEG rather than EEG, assessed the sources of the M170 and Gamma oscillations using beamformer, and explored the sensitivity of these neural manifestations to global, featural and configural information in faces. The M170 was larger in response to faces and face components than in response to watches. Scrambling the configuration of the inner components of the face even if presented without the face contour reduced and delayed the M170. The amplitude of MEG Gamma oscillations (30-70 Hz) was higher than baseline during an epoch between 230-570 ms from stimulus onset and was particularly sensitive to the configuration of the stimuli, regardless of their category. However, in the lower part of this frequency range (30-40 Hz) only physiognomic stimuli elevated the MEG above baseline. Both the M170 and Gamma were generated in a posterior-ventral network including the fusiform, inferior-occipital and lingual gyri, all in the right hemisphere. The generation of Gamma involved additional sources in the visual system, bilaterally. We suggest that the evoked M170 manifests a face-perception mechanism based on the global characteristics of face, whereas the induced Gamma oscillations are associated with the integration of visual input into a pre-existent coherent perceptual representation.

Spectral and phase-coherence correlates of impaired auditory mismatch negativity (MMN) in schizophrenia: A MEG study.

BACKGROUND: Reduced auditory mismatch negativity (MMN) is robustly impaired in schizophrenia. However, mechanisms underlying dysfunctional MMN generation remain incompletely understood. This study aimed to examine the role of evoked spectral power and phase-coherence towards deviance detection and its impairments in schizophrenia. METHODS: Magnetoencephalography data was collected in 16 male schizophrenia patients and 16 male control participants during an auditory MMN paradigm. Analyses of event-related fields (ERF), spectral power and inter-trial phase-coherence (ITPC) focused on Heschl's gyrus, superior temporal gyrus, inferior/medial frontal gyrus and thalamus. RESULTS: MMNm ERF amplitudes were reduced in patients in temporal, frontal and subcortical regions, accompanied by decreased theta-band responses, as well as by a diminished gamma-band response in auditory cortex. At theta/alpha frequencies, ITPC to deviant tones was reduced in patients in frontal cortex and thalamus. Patients were also characterized by aberrant responses to standard tones as indexed by reduced theta-/alpha-band power and ITPC in temporal and frontal regions. Moreover, stimulus-specific adaptation was decreased at theta/alpha frequencies in left temporal regions, which correlated with reduced MMNm spectral power and ERF amplitude. Finally, phase-reset of alpha-oscillations after deviant tones in left thalamus was impaired, which correlated with impaired MMNm generation in auditory cortex. Importantly, both non-rhythmic and rhythmic components of spectral activity contributed to the MMNm response. CONCLUSIONS: Our data indicate that deficits in theta-/alpha- and gamma-band activity in cortical and subcortical regions as well as impaired spectral responses to standard sounds could constitute potential mechanisms for dysfunctional MMN generation in schizophrenia, providing a novel perspective towards MMN deficits in the disorder.

The dual neural effects of oxytocin in autistic youth: results from a randomized trial.

Recent discoveries have highlighted the effects of oxytocin (OT) on social behavior and perception among autistic individuals. However, a gap persists in the literature regarding the potential effects of OT and the neural temporal dynamics due to OT administration. We explored the effect of OT on autistic individuals using magnetoencephalography (MEG), focusing on M100, M170, and M250, social perception-related components that tend to show atypical patterns in autistic individuals. Twenty-five autistic adolescents participated in this randomized, double-blind MEG study. Autistic individuals arrived at the lab twice and received an acute dose of intranasal OT or placebo in each session. During the scans, participants were asked to identify pictures of social and non-social stimuli. Additionally, 23 typically developing (TD) adolescents performed the same task in the MEG as a benchmark that allowed us to better characterize neural regions of interest and behavioral results for this age group in this task. A source-model beamformer analysis revealed that OT enhanced neural activity for social stimuli in frontal regions during M170. Additionally, in each of the preselected time windows, OT increased activation in the left hemisphere, regardless of the content of the presented stimuli. We suggest that OT increased the processing of social stimuli through two separate mechanisms. First, OT increased neural activity in a nonspecific manner, allowing increased allocation of attention toward the stimuli. Second, OT enhanced M170 activity in frontal regions only in response to social stimuli. These results reveal the temporal dynamics of the effects of OT on the early stages of social and non-social perception in autistic adolescents.Trial registration: This study was a part of a project registered as clinical trial October 27th, 2021. ClinicalTrials.gov Identifier: NCT05096676.

Oxytocin impacts top-down and bottom-up social perception in adolescents with ASD: a MEG study of neural connectivity.

BACKGROUND: In the last decade, accumulative evidence has shown that oxytocin can modulate social perception in typically developed individuals and individuals diagnosed with autism. While several studies show that oxytocin (OT) modulates neural activation in social-related neural regions, the mechanism that underlies OT effects in ASD is not fully known yet. Despite evidence from animal studies on connections between the oxytocinergic system and excitation/inhibition neural balance, the influence of OT on oscillatory responses among individuals with ASD has been rarely examined. To bridge these gaps in knowledge, we investigated the effects of OT on both social and non-social stimuli while focusing on its specific influence on the neural connectivity between three socially related neural regions-the left and right fusiform and the medial frontal cortex. METHODS: Twenty-five adolescents with ASD participated in a wall-established social task during a randomized, double-blind placebo-controlled MEG and OT administration study. Our main task was a social-related task that required the identification of social and non-social-related pictures. We hypothesized that OT would modulate the oscillatory connectivity between three pre-selected regions of interest to be more adaptive to social processing. Specifically, we focused on alpha and gamma bands which are known to play an important role in face processing and top-down/bottom-up balance. RESULTS: Compared to placebo, OT reduced the connectivity between the medial frontal cortex and the fusiform in the low gamma more for social stimuli than for non-social ones, a reduction that was correlated with individuals' performance in the task. Additionally, for both social and non-social stimuli, OT increased the connectivity in the alpha and beta bands. LIMITATIONS: Sample size was determined based on sample sizes previously reported in MEG in clinical populations, especially OT administration studies in combination with neuroimaging in ASD. We were limited in our capability to recruit for such a study, and as such, the sample size was not based on a priori power analysis. Additionally, we limited our analyses to specific neural bands and regions. To validate the current results, future studies may be needed to explore other parameters using whole-brain approaches in larger samples. CONCLUSION: These results suggest that OT influenced social perception by modifying the communication between frontal and posterior regions, an attenuation that potentially impacts both social and non-social early perception. We also show that OT influences differ between top-down and bottom-up processes, depending on the social context. Overall, by showing that OT influences both social-related perception and overall attention during early processing stages, we add new information to the existing understanding of the impact of OT on neural processing in ASD. Furthermore, by highlighting the influence of OT on early perception, we provide new directions for treatments for difficulties in early attentional phases in this population. Trial registration Registered on October 27, 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05096676 (details on clinical registration can be found in www. CLINICALTRIAL: gov , unique identifier: NCT05096676 ).

Dialogue intervention for youth amidst intractable conflict attenuates neural prejudice response and promotes adults' peacemaking.

Humans' dependence on group living has led to the formation of tenacious, often nonconscious negative perceptions of other social groups, a phenomenon termed "intergroup bias" that sustains one of the world's most imminent problem: intergroup conflicts. Adolescents' participation in intergroup conflicts has been continuously on the rise, rendering the need to devise interventions that can mitigate some of their deleterious effects on youth an urgent societal priority. Framed within the Israeli-Palestinian conflict and targeting youth, we implemented a dialogue-enhancing intervention for adolescents (16 to 18 years) reared amidst intractable conflict that builds on social synchrony and the neurobiology of affiliation. Implementing a randomized controlled trial design, before and after the 8-week intervention adolescents underwent magnetoencephalography to assess a neural marker of implicit prejudice and interviewed on their attitudes toward the conflict. Adolescents who received the intervention showed attenuation of the neural prejudice response, as indexed by sustained occipital alpha that was significantly reduced at post-intervention and adopted attitudes of peacemaking. Change in the neural prejudice response predicted attitudes of compromise and support in peacebuilding 7 years later, when young adults can already engage in active civil duties and responsibilities. These results underscore adolescence as a window of opportunity for enhancing inter-group dialogue and demonstrate the long-term associations between the neural evaluation of prejudice and self-reported measures of proclivity for compromise and peace in the context of an intractable century-long conflict.

Neural rhythmic underpinnings of intergroup bias: implications for peace-building attitudes and dialogue.

Intergroup bias is a ubiquitous socio-cognitive phenomenon that, while sustaining human dependence on group living, often leads to prejudice, inequity, and violence; yet, its neural underpinnings remain unclear. Framed within the Israeli-Palestinian conflict and targeting youth, this study utilized magnetoencephalography to describe intrinsic neural oscillatory processes that represent the intergroup bias and may link with engagement in peacemaking in order to shed further light on the neural mechanisms underpinning intergroup conflict. Across the oscillatory spectrum, from very low to very high frequency bands, the only rhythm found to underlie the intergroup bias was the alpha rhythm. Alpha rhythm was continuously activated across the task and integrated a rapid perceptual component in the occipital cortex with a top-down cognitive-control component in the medial cingulate cortex. These components were distinctly associated with the real-life intergroup dialogue style and expressed attitudes that promote active engagement in peacemaking. Our findings suggest that the cortical alpha rhythm plays a crucial role in sustaining intergroup bias and addresses its impact on concrete intergroup experiences. The results highlight the need to provide opportunities for active peace-building dialogue to youth reared amidst intractable conflicts.

Neural oscillations while remembering traumatic memories in post-traumatic stress disorder.

OBJECTIVE: The current study investigated the oscillatory brain activity of PTSD patients during directed and imaginal exposure to the traumatic memory using magnetoencephalography (MEG), in a paradigm resembling exposure therapy. METHODS: Brain activity of healthy trauma-exposed controls and PTSD participants was measured with MEG as they listened to individualized trauma narratives as well as to a neutral narrative and as they imagined the narrative in detail. Source localization analysis by frequency bands was conducted in order to map neural generators of oscillatory activity. RESULTS: Elicitation of traumatic memories resulted in a distinct neural pattern in PTSD patients compared to healthy trauma-exposed individuals. In response to trauma scripts PTSD patients showed increases in high-gamma band power in visual areas, increased frontal and temporal theta as well as prefrontal alpha and medial temporal beta power relative to neutral scripts. CONCLUSIONS: Results suggest that when recollecting and imagining traumatic memories PTSD patients attempt to engage control or inhibition mechanisms. However, these are either not successfully recruited or inefficient leading to heightened responses and recollection. SIGNIFICANCE: Investigating the oscillatory neural dynamics of PTSD patients can help us better understand the processes underlying trauma re-experiencing.

Localization of beta power decrease as measure for lateralization in pre-surgical language mapping with magnetoencephalography, compared with functional magnetic resonance imaging and validated by Wada test.

Objective: Atypical patterns of language lateralization due to early reorganizational processes constitute a challenge in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. There is no consensus on an optimal analysis method used for the identification of language dominance in MEG. This study examines the concordance between MEG source localization of beta power desynchronization and fMRI with regard to lateralization and localization of expressive and receptive language areas using a visual verb generation task. Methods: Twenty-five patients with pharmaco-resistant epilepsy, including six patients with atypical language lateralization, and ten right-handed controls obtained MEG and fMRI language assessment. Fourteen patients additionally underwent the Wada test. We analyzed MEG beta power desynchronization in sensor (controls) and source space (patients and controls). Beta power decrease between 13 and 35 Hz was localized applying Dynamic Imaging of Coherent Sources Beamformer technique. Statistical inferences were grounded on cluster-based permutation testing for single subjects. Results: Event-related desynchronization of beta power in MEG was seen within the language-dominant frontal and temporal lobe and within the premotor cortex. Our analysis pipeline consistently yielded left language dominance with high laterality indices in controls. Language lateralization in MEG and Wada test agreed in all 14 patients for inferior frontal, temporal and parietal language areas (Cohen's Kappa = 1, p < 0.001). fMRI agreed with Wada test in 12 out of 14 cases (85.7%) for Broca's area (Cohen's Kappa = 0.71, p = 0.024), while the agreement for temporal and temporo-parietal language areas were non-significant. Concordance between MEG and fMRI laterality indices was highest within the inferior frontal gyrus, with an agreement in 19/24 cases (79.2%), and non-significant for Wernicke's area. Spatial agreement between fMRI and MEG varied considerably between subjects and brain regions with the lowest Euclidean distances within the inferior frontal region of interest. Conclusion: Localizing the desynchronization of MEG beta power using a verb generation task is a promising tool for the identification of language dominance in the pre-surgical evaluation of epilepsy patients. The overall agreement between MEG and fMRI was lower than expected and might be attributed to differences within the baseline condition. A larger sample size and an adjustment of the experimental designs are needed to draw further conclusions.

High-gamma oscillations as neurocorrelates of ADHD: A MEG crossover placebo-controlled study.

Attention Deficit Hyperactive Disorder (ADHD) is a common neurobehavioral disorder with a significant and pervasive impact on patients' lives. Identifying neurophysiological correlates of ADHD is important for understanding its underlying mechanisms, as well as for improving clinical accuracy beyond cognitive and emotional factors. The present study focuses on finding a diagnostic stable neural correlate based on evaluating MEG resting state frequency bands. Twenty-two ADHD patients and 23 controls adults were blindly randomized to two methylphenidate/placebo evaluation days. On each evaluation day state anxiety was assessed, a 2N-back executive function task was performed, and resting state MEG brain activity was recorded at three timepoints. A frequency-based cluster analysis yielded higher high-gamma power for ADHD over posterior sensors and lower high-gamma power for ADHD over frontal-central sensors. These results were shown to be stable over three measurements, unaffected by methylphenidate treatment, and linked to cognitive accuracy and state anxiety. Furthermore, the differential high-gamma activity evidenced substantial ADHD diagnostic efficacy, comparable to the cognitive and emotional factors. These results indicate that resting state high-gamma activity is a promising, stable, valid and diagnostically-relevant neurocorrelate of ADHD. Due to the evolving understanding both in the cellular and network level of high-gamma oscillations, focusing future studies on this frequency band bears the potential for a better understanding of ADHD, thus advancing the specificity of the evaluation of the disorder and developing new tools for therapy.

Mapping Cell Viability Quantitatively and Independently From Cell Density in 3D Gels Noninvasively.

OBJECTIVE: In biomanufacturing there is a need for quantitative methods to map cell viability and density inside 3D bioreactors to assess health and proliferation over time. Recently, noninvasive MRI readouts of cell density have been achieved. However, the ratio of live to dead cells was not varied. Herein we present an approach for measuring the viability of cells embedded in a hydrogel independently from cell density to map cell number and health. METHODS: Independent quantification of cell viability and density was achieved by calibrating the 1H magnetization transfer- (MT) and diffusion-weighted NMR signals to samples of known cell density and viability using a multivariate approach. Maps of cell viability and density were generated by weighting NMR images by these parameters post-calibration. RESULTS: Using this method, the limits of detection (LODs) of total cell density and viable cell density were found to be 3.88 ×108 cells · mL -1· Hz -1/2 and 2.36 ×109 viable cells · mL -1· Hz -1/2 respectively. CONCLUSION: This mapping technique provides a noninvasive means of visualizing cell viability and number density within optically opaque bioreactors. SIGNIFICANCE: We anticipate that such nondestructive readouts will provide valuable feedback for monitoring and controlling cell populations in bioreactors.