Memory retrieval brain-behavior disconnection in mild traumatic brain injury: A magnetoencephalography and diffusion tensor imaging study.

Mild traumatic brain (mTBI) injury is often associated with long-term cognitive and behavioral complications, including an increased risk of memory impairment. Current research challenges include a lack of cross-modal convergence regarding the underlying neural-behavioral mechanisms of mTBI, which hinders therapeutics and outcome management for this frequently under-treated and vulnerable population. We used multi-modality imaging methods including magnetoencephalography (MEG) and diffusion tensor imaging (DTI) to investigate brain-behavior impairment in mTBI related to working memory. A total of 41 participants were recruited, including 23 patients with a first-time mTBI imaged within 3 months of injury (all male, age = 29.9, SD = 6.9), and 18 control participants (all male, age = 27.3, SD = 5.3). Whole-brain statistics revealed spatially concomitant functional-structural disruptions in brain-behavior interactions in working memory in the mTBI group compared with the control group. These disruptions are located in the hippocampal-prefrontal region and, additionally, in the amygdala (measured by MEG neural activation and DTI measures of fractional anisotropy in relation to working memory performance; p < .05, two-way ANCOVA, nonparametric permutations, corrected). Impaired brain-behavior connections found in the hippocampal-prefrontal and amygdala circuits indicate brain dysregulation of memory, which may leave mTBI patients vulnerable to increased environmental demands exerting memory resources, leading to related cognitive and emotional psychopathologies. The findings yield clinical implications and highlight a need for early rehabilitation after mTBI, including attention- and sensory-based behavioral exercises.

Epilepsy disrupts hippocampal phase precision and impairs working memory.

OBJECTIVE: Working memory deficits are prevalent in childhood epilepsy. Working memory processing is thought to be supported by the phase of hippocampal neural oscillations. Disruptions in working memory have previously been linked to the occurrence of transient epileptic activity. This study aimed to resolve the associations between oscillatory neural activity, transient epileptiform events, and working memory in children with epilepsy. METHODS: Intracranial recordings were acquired from stereotactically implanted electrodes in the hippocampi, epileptogenic zones, and working memory-related networks of children with drug-resistant epilepsy during a 1-back working memory task. Interictal epileptic activity was captured using automated detectors. Hippocampal phase and interregional connectivity within working memory networks were indexed by Rayleigh Z and the phase difference derivative, respectively. Trials with and without transient epileptiform events were compared. RESULTS: Twelve children (mean age = 14.3 ± 2.8 years) with drug-resistant epilepsy were included in the study. In the absence of transient epileptic activity, significant delta and theta hippocampal phase resetting occurred in response to working memory stimulus presentation (Rayleigh z-score = 9, Rayleigh z-score = 8). Retrieval trials that were in phase with the preferred phase angle were associated with faster reaction times (p = .01, p = .03). Concurrently, delta and theta coordinated interactions between the hippocampi and working memory-related networks were enhanced (phase difference derivative [PDD] z-scores = 6-11). During retrieval trials with pre-encoding or pre-retrieval transient epileptic activity, phase resetting was attenuated (Rayleigh z-score = 5, Rayleigh z-score = 1), interregional connectivity was altered (PDD z-scores = 1-3), and reaction times were prolonged (p = .01, p = .03). SIGNIFICANCE: This work highlights the role of hippocampal phase in working memory. We observe poststimulus hippocampal phase resetting coincident with enhanced interregional connectivity. The precision of hippocampal phase predicts optimal working memory processing, and transient epileptic activity prolongs working memory processing. These findings can help guide future treatments aimed at restoring memory function in this patient population.

Phase Resetting in the Anterior Cingulate Cortex Subserves Childhood Attention and Is Impaired by Epilepsy.

The neural mechanisms that underlie selective attention in children are poorly understood. By administering a set-shifting task to children with intracranial electrodes stereotactically implanted within anterior cingulate cortex (ACC) for epilepsy monitoring, we demonstrate that selective attention in a set-shifting task is dependent upon theta-band phase resetting immediately following stimulus onset and that the preferred theta phase angle is predictive of reaction time during attentional shift. We also observe selective enhancement of oscillatory coupling between the ACC and the dorsal attention network and decoupling with the default mode network during task performance. When transient focal epileptic activity occurs around the time of stimulus onset, phase resetting is impaired, connectivity changes with attentional and default mode networks are abolished, and reaction times are prolonged. The results of the present work highlight the fundamental mechanistic role of oscillatory phase in ACC in supporting attentional circuitry and present novel opportunities to remediate attention deficits in children with epilepsy.

Characterizing Inscapes and resting-state in MEG: Effects in typical and atypical development.

Examining the brain at rest is a powerful approach used to understand the intrinsic properties of typical and disordered human brain function, yet task-free paradigms are associated with greater head motion, particularly in young and/or clinical populations such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Inscapes, a non-social and non-verbal movie paradigm, has been introduced to increase attention, thus mitigating head motion, while reducing the task-induced activations found during typical movie watching. Inscapes has not yet been validated for use in magnetoencephalography (MEG), and it has yet to be shown whether its effects are stable in clinical populations. Across typically developing (N = 32) children and adolescents and those with ASD (N = 46) and ADHD (N = 42), we demonstrate that head motion is reduced during Inscapes. Due to the task state evoked by movie paradigms, we also expectedly observed concomitant modulations in local neural activity (oscillatory power) and functional connectivity (phase and envelope coupling) in intrinsic resting-state networks and across the frequency spectra compared to a fixation cross resting-state. Increases in local activity were accompanied by decreases in low-frequency connectivity within and between resting-state networks, primarily the visual network, suggesting that task-state evoked by Inscapes moderates ongoing and spontaneous cortical inhibition that forms the idling intrinsic networks found during a fixation cross resting-state. Importantly, these effects were similar in ASD and ADHD, making Inscapes a well-suited advancement for investigations of resting brain function in young and clinical populations.

Sex-differences in network level brain dynamics associated with pain sensitivity and pain interference.

Neural dynamics can shape human experience, including pain. Pain has been linked to dynamic functional connectivity within and across brain regions of the dynamic pain connectome (consisting of the ascending nociceptive pathway (Asc), descending antinociceptive pathway (Desc), salience network (SN), and the default mode network (DMN)), and also shows sex differences. These linkages are based on fMRI-derived slow hemodynamics. Here, we utilized the fine temporal resolution of magnetoencephalography (MEG) to measure resting state functional coupling (FCp) related to individual pain perception and pain interference in 50 healthy individuals (26 women, 24 men). We found that pain sensitivity and pain interference were linked to within- and cross-network broadband FCp across the Asc and SN. We also identified sex differences in these relationships: (a) women exhibited greater within-network static FCp, whereas men had greater dynamic FCp within the dynamic pain connectome; (b) relationship between pain sensitivity and pain interference with FCp in women was commonly found in theta, whereas in men, these relationships were predominantly in the beta and low gamma bands. These findings indicate that dynamic interactions of brain networks underlying pain involve fast brain communication in men but slower communication in women.

Interhemispheric auditory connectivity requires normal access to sound in both ears during development.

Despite early bilateral cochlear implantation, children with congenital deafness do not develop accurate spatial hearing; we thus asked whether auditory brain networks are disrupted in these children. EEG responses were evoked unilaterally and bilaterally in 13 children with normal hearing and 16 children receiving bilateral cochlear implants simultaneously. Active cortical areas were estimated by the Time Restricted Artifact and Coherent source Suppression (TRACS) beamformer and connected cortical areas were identified by measuring coherence between source responses. A whole-brain analysis of theta band coherence revealed the strongest connections between the temporal areas in all conditions at early latencies. Stronger imaginary coherence in activity between the two auditory cortices to bilateral than unilateral input was found in children with normal hearing reflecting facilitation in the auditory network during bilateral hearing. The opposite effect, depressed coherence, was found during bilateral stimulation in children using cochlear implants. Children with cochlear implants also showed a unique auditory network in response to bilateral stimulation which was marked by increased connectivity between occipital and frontal areas. These findings suggest that cortical networks for sound processing are normally facilitated by bilateral input but are disrupted in children who hear through two independent cochlear implants. Efforts to improve hearing in children with congenital deafness must thus include corrections to potential mismatches in bilateral input to support brain development.

Local and large-scale beta oscillatory dysfunction in males with mild traumatic brain injury.

Mild traumatic brain injury (mTBI) is impossible to detect with standard neuroradiological assessment such as structural magnetic resonance imaging (MRI). Injury does, however, disrupt the dynamic repertoire of neural activity indexed by neural oscillations. In particular, beta oscillations are reliable predictors of cognitive, perceptual, and motor system functioning, as well as correlating highly with underlying myelin architecture and brain connectivity-all factors particularly susceptible to dysregulation after mTBI. We measured local and large-scale neural circuit function by magnetoencephalography (MEG) with a data-driven model fit approach using the fitting oscillations and one-over f algorithm in a group of young adult men with mTBI and a matched healthy control group. We quantified band-limited regional power and functional connectivity between brain regions. We found reduced regional power and deficits in functional connectivity across brain areas, which pointed to the well-characterized thalamocortical dysconnectivity associated with mTBI. Furthermore, our results suggested that beta functional connectivity data reached the best mTBI classification performance compared with regional power and symptom severity [measured with Sport Concussion Assessment Tool 2 (SCAT2)]. The present study reveals the relevance of beta oscillations as a window into neurophysiological dysfunction in mTBI and also highlights the reliability of neural synchrony biomarkers in disorder classification.NEW & NOTEWORTHY Mild traumatic brain injury (mTBI) disrupts the dynamic repertoire of neural oscillations, but so far beta activity has not been studied. In mTBI, we found reductions in frontal beta and large-scale beta networks, indicative of thalamocortical dysconnectivity and disrupted information flow through cortico-basal ganglia-thalamic circuits. Relatively, connectivity more accurately classifies individual mTBI cases compared with regional power. We show the relevance of beta oscillations in mTBI and the reliability of these markers in classification.

The effect of mild traumatic brain injury on the visual processing of global form and motion.

Cortical visual processing involves the ventral stream (form perception) and the dorsal stream (motion perception). We assessed whether mild traumatic brain injury (TBI) differentially affects these two streams. Eleven adults with mild TBI (28 ± 9 yrs, 17 ± 5 months post injury) and 25 controls (25 ± 5 yrs) participated. Participants completed tests of global processing involving Glass patterns (form) and random dot kinematograms (motion), measurement of contrast thresholds for motion direction discrimination, a comprehensive vision screening and the Post-Concussion Symptom Inventory (PCSI). Our results showed that the mild TBI group had significantly higher (worse) global form (mean ± SD: TBI 25 ± 6%, control 21 ± 5%) and motion (TBI 14 ± 7%, control 11 ± 3%) coherence thresholds than controls. The magnitude of the mild TBI group deficit did not differ between the two tasks. Contrast thresholds for motion direction discrimination did not differ between the groups, but were positively correlated with PCSI score (r2 = 0.51. p = 0.01) in the mild TBI group. The mild TBI group had worse outcomes than controls for all clinical measurements of vision except distance visual acuity. In conclusion, mild TBI affects processing in both the dorsal and ventral cortical processing streams equally. In addition, spatiotemporal contrast sensitivity may be related to the symptoms of mild TBI.

Post-Traumatic Stress Constrains the Dynamic Repertoire of Neural Activity.

Post-traumatic stress disorder (PTSD) is an anxiety disorder arising from exposure to a traumatic event. Although primarily defined in terms of behavioral symptoms, the global neurophysiological effects of traumatic stress are increasingly recognized as a critical facet of the human PTSD phenotype. Here we use magnetoencephalographic recordings to investigate two aspects of information processing: inter-regional communication (measured by functional connectivity) and the dynamic range of neural activity (measured in terms of local signal variability). We find that both measures differentiate soldiers diagnosed with PTSD from soldiers without PTSD, from healthy civilians, and from civilians with mild traumatic brain injury, which is commonly comorbid with PTSD. Specifically, soldiers with PTSD display inter-regional hypersynchrony at high frequencies (80-150 Hz), as well as a concomitant decrease in signal variability. The two patterns are spatially correlated and most pronounced in a left temporal subnetwork, including the hippocampus and amygdala. We hypothesize that the observed hypersynchrony may effectively constrain the expression of local dynamics, resulting in less variable activity and a reduced dynamic repertoire. Thus, the re-experiencing phenomena and affective sequelae in combat-related PTSD may result from functional networks becoming "stuck" in configurations reflecting memories, emotions, and thoughts originating from the traumatizing experience. SIGNIFICANCE STATEMENT: The present study investigates the effects of post-traumatic stress disorder (PTSD) in combat-exposed soldiers. We find that soldiers with PTSD exhibit hypersynchrony in a circuit of temporal lobe areas associated with learning and memory function. This rigid functional architecture is associated with a decrease in signal variability in the same areas, suggesting that the observed hypersynchrony may constrain the expression of local dynamics, resulting in a reduced dynamic range. Our findings suggest that the re-experiencing of traumatic events in PTSD may result from functional networks becoming locked in configurations that reflect memories, emotions, and thoughts associated with the traumatic experience.

Increased Frontal Lobe Activation After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Neurocognitive deficits are common among survivors of aneurysmal subarachnoid hemorrhage, even among those with good outcomes and no structural lesions. This study aims to probe the neurophysiological underpinnings of cognitive dysfunction among patients with ruptured intracranial aneurysms using magnetoencephalography (MEG). METHODS: Thirteen patients who had undergone uncomplicated coiling for aneurysmal subarachnoid hemorrhage and 13 matched controls were enrolled. Neuropsychological tests were done before magnetoencephalography scans. Magnetoencephalography data were acquired in a 151-channel, whole-head magnetoencephalography system for resting state and 2 cognitive tasks (go-no-go and set-shifting). Mean time from treatment to test was 18.8 months. RESULTS: Cognitive tasks of inhibition (go-no-go) indicated greater activation in the right anterior cingulate and inferior frontal gyrus, and cognitive set-shifting tasks (mental flexibility) indicated greater activity in the bilateral anterior cingulate cortex and right medial frontal gyrus among aneurysmal subarachnoid hemorrhage patients, with significantly different timing of activation between groups. Resting-state, beta-band connectivity of the anterior cingulate correlated negatively with Montreal Cognitive Assessment scores (left: r=-0.56; P<0.01 and right: r=-0.55; P<0.01): higher connectivity of this region was linked to poorer cognitive test performance. CONCLUSIONS: We have shown increased activation in areas of the anterior cingulate gyrus and frontobasal regions during the execution of more demanding tasks in good grade. The degree of activation in the anterior cingulate gyrus has a negative correlation with cognitive (Montreal Cognitive Assessment) scores. These subtle differences may be related to the common neurocognitive and behavioral complaints seen in this patient population.

Evidence that smooth pursuit velocity, not eye position, modulates alpha and beta oscillations in human middle temporal cortex.

Suppression of 5-25 Hz oscillations have been observed in MT+ during pursuit eye movements, suggesting oscillations that play a role in oculomotor control and/or the integration of extraretinal signals during pursuit. The amplitude of these rhythms appears to covary with head-centered eye position, but an alternative is that they depend on a velocity signal that lags the movement of the eyes. To investigate, we explored how alpha and beta amplitude changes related to ongoing eye movement depended on pursuit at different eccentricities. The results revealed largely identical patterns of modulation in the alpha and beta amplitude, irrespective of the eccentricity at which the pursuit eye movement was performed. The signals we measured therefore do not depend on head-centered position. A second experiment was designed to investigate whether the alpha and beta oscillations depended on the direction of pursuit, as opposed to just speed. We found no evidence that alpha or beta oscillations depended on direction, but there was a significant effect of eye speed on the magnitude of the beta suppression. This suggests distinct functional roles for alpha and beta suppression in pursuit behavior.

Almost winning: induced MEG theta power in insula and orbitofrontal cortex increases during gambling near-misses and is associated with BOLD signal and gambling severity.

In slot machine gambling, the "near-miss effect" (when a losing display physically resembles an actual win display) has been implicated in pathological gambling (PG). Functional magnetic resonance imaging (fMRI) with PG and non-PG participants shows that near-misses recruit reward-related circuitry, but little is known about the temporal dynamics and oscillatory changes underlying near-misses. The present multi-modal imaging study investigated the near-miss effect by combining the spatial resolution of blood oxygen-level dependent (BOLD)-fMRI with the spatial and temporal resolution of magnetoencephalography (MEG) during a slot machine task in PG and non-PG groups. Given previous findings on outcome (win and near-miss) processing, functional overlap was hypothesized between induced changes in temporal oscillations and BOLD response to wins and near-misses in PG. We first validated our task in a sample of varying gambling severity using BOLD-fMRI and then compared PG and non-PG participants using MEG to investigate changes in induced oscillatory power associated with win and near-miss, relative to loss, outcomes. Across both modalities, near-misses recruited similar brain regions to wins, including right inferior frontal gyrus and insula. Using MEG, increased theta-band (4-7Hz) oscillations to near-misses were observed in the insula and right orbitofrontal cortex (OFC). Furthermore, this theta-band activity was positively associated with gambling severity. These findings demonstrate that the near-miss effect in insula and OFC is associated with induced theta oscillations. The significance of these findings for theories of PG and the development of potential biomarkers and therapeutic targets is discussed.

Cortical oscillatory changes in human middle temporal cortex underlying smooth pursuit eye movements.

Extra-striate regions are thought to receive non-retinal signals from the pursuit system to maintain perceptual stability during eye movements. Here, we used magnetoencephalography (MEG) to study changes in oscillatory power related to smooth pursuit in extra-striate visual areas under three conditions: 'pursuit' of a small target, 'retinal motion' of a large background and 'pursuit + retinal motion' combined. All stimuli moved sinusoidally. MEG source reconstruction was performed using synthetic aperture magnetometry. Broadband alpha-beta suppression (5-25 Hz) was observed over bilateral extra-striate cortex (consistent with middle temporal cortex (MT+)) during all conditions. A functional magnetic resonance imaging study using the same experimental protocols confirmed an MT+ localisation of this extra-striate response. The alpha-beta envelope power in the 'pursuit' condition showed a hemifield-dependent eye-position signal, such that the global minimum in the alpha-beta suppression recorded in extra-striate cortex was greatest when the eyes were at maximum contralateral eccentricity. The 'retinal motion' condition produced sustained alpha-beta power decreases for the duration of stimulus motion, while the 'pursuit + retinal motion' condition revealed a double-dip 'W' shaped alpha-beta envelope profile with the peak suppression contiguous with eye position when at opposing maximum eccentricity. These results suggest that MT+ receives retinal as well as extra-retinal signals from the pursuit system as part of the process that enables the visual system to compensate for retinal motion during eye movement. We speculate that the suppression of the alpha-beta rhythm reflects either the integration of an eye position-dependent signal or one that lags the peak velocity of the sinusoidally moving target.

A Scoping Review of Magnetic Resonance Modalities Used in Detection of Persistent Postconcussion Symptoms in Pediatric Populations.

Up to 30% of youth with concussion experience PPCSs (PPCS) lasting 4 weeks or longer, and can significantly impact quality of life. Magnetic resonance imaging (MRI) has the potential to increase understanding of causal mechanisms underlying PPCS. However, there are no clear modalities to assist in detecting PPCS. This scoping review aims to synthesize findings on utilization of MRI among children and youth with PPCS, and summarize progress and limitations. Thirty-six studies were included from 4907 identified papers. Many studies used multiple modalities, including (1) structural (n = 27) such as T1-weighted imaging, diffusion weighted imaging, and susceptibility weighted imaging; and (2) functional (n = 23) such as functional MRI and perfusion-weighted imaging. Findings were heterogeneous among modalities and regions of interest, which warrants future reviews that report on the patterns and potential advancements in the field. Consideration of modalities that target PPCS prediction and sensitive modalities that can supplement a biopsychosocial approach to PPCS would benefit future research.

Brain network properties of clinical versus subclinical seizures among critically ill children.

OBJECTIVE: Electrographic seizures are common among critically ill children, and have been associated with worse outcomes. Despite their often-widespread cortical representation, most of these seizures remain subclinical, a phenomenon which remains poorly understood. We compared the brain network properties of clinical versus subclinical seizures to gain insight into their relative potential deleterious effects. METHODS: Functional connectivity (phase lag index) and graph measures (global efficiency and clustering coefficients) were computed for 2178 electrographic seizures recorded during 48-hours of 19-channel continuous EEG monitoring obtained in 20 comatose children. Frequency-specific group differences in clinical versus subclinical seizures were analyzed using a non-parametric ANCOVA, adjusting for age, sex, medication exposure, treatment intensity and seizures per subject. RESULTS: Clinical seizures demonstrated greater functional connectivity than subclinical seizures at alpha frequencies, but less connectivity than subclinical seizures at delta frequencies. Clinical seizures also demonstrated significantly higher median global efficiency than subclinical seizures (p < 0.01), and significantly higher median clustering coefficients across all electrodes at alpha frequencies. CONCLUSIONS: Clinical expression of seizures correlates with greater alpha synchronization of distributed brain networks. SIGNIFICANCE: The stronger global and local alpha-mediated functional connectivity observed during clinical seizures may indicate greater pathological network recruitment. These observations motivate further studies to investigate whether the clinical expression of seizures may influence their potential to cause secondary brain injury.

Cortical Gyrification Morphology in Adult Males with Mild Traumatic Brain Injury.

Cortical gyrification, as a specific measure derived from magnetic resonance imaging, remains understudied in mild traumatic brain injury (mTBI). Local gyrification index (lGI) and mean curvature are related measures indexing the patterned folding of the cortex,ml which reflect distinct properties of cortical morphology and geometry. Using both metrics, we examined cortical gyrification morphology in 59 adult males with mTBI (n = 29) versus those without (n = 30) mTBI in the subacute phase of injury (between 2 weeks and 3 months). The effect of IQ on lGI and brain-symptom relations were also examined. General linear models revealed greater lGI in mTBI versus controls in the frontal lobes bilaterally, but reduced lGI in mTBI of the left temporal lobe. An age-related decrease in lGI was found in numerous areas, with no significant group-by-age interaction effects observed. Including other factors (i.e., mTBI severity, symptoms, and IQ) in the lGI model yielded similar results with few exceptions. Mean curvature analyses depicted a significant group-by-age interaction with the absence of significant main effects of group or age. Our results suggest that cortical gyrification morphology is adversely affected by mTBI in both frontal and temporal lobes, which are thought of as highly susceptible regions to mTBI. These findings contribute to understanding the effects of mTBI on neuromorphological properties, such as alterations in cortical gyrification, which reflect underlying microstructural changes (i.e., apoptosis, neuronal number, or white matter alterations). Future studies are needed to infer causal relationships between micro- and macrostructural changes after an mTBI and investigate potential sex differences.

Mental Health Outcomes Across the Lifespan in Individuals With Persistent Post-Concussion Symptoms: A Scoping Review.

Objective: Concussion is a common yet heterogenous injury. Approximately 15-30% of cases present with persistent post-concussion symptoms (PPCS), continuing 4 weeks or more post-injury in children, youth, and adolescents, and 3 months or more in adults. There are known bidirectional links between PPCS and mental health outcomes. The focus of this scoping review is to explore the literature on mental health outcomes in individuals experiencing PPCS. Research objectives were to explore: (1) the mental health outcomes of individuals with PPCS and types of assessments used to identify mental health outcomes this group, and (2) how mental health outcomes compare in terms of similarities and differences among pediatric and adult populations with PPCS. Method: Ovid MEDLINE; EMBASE; CINAHL, and PsycInfo databases were searched. After title and abstract screening of 11,920 studies, 481 articles were reviewed. Twenty-five papers met inclusion criteria. Results were organized by mental health outcomes of pediatric and adult populations, separately. Results: There was a significantly higher number of studies devoted to adult populations. Of the 25 studies, 19 (76%) focused on adults, while six (24%) focused on adolescents. In adult populations, studies focused on symptoms of: anxiety (n = 2), depression (n = 8), and anxiety and depression (n = 9). Two studies assessed other emotional outcomes (10.5%). Within pediatric populations, an equal number of studies explored symptoms of: anxiety (n = 2), depression (n = 2), and anxiety and depression (n = 2). No studies focused on other emotional outcomes. Studies ranged greatly in methods, design, and control group. Most studies reported higher psychiatric symptoms of anxiety and/or depression in those with PPCS compared to individuals with recovered concussion or healthy controls. Discussion: This review contributes to the understanding of mental health outcomes in those experiencing PPCS. Mental health and PPCS requires greater attention in pediatric populations, and consider strategies for those experiencing PPCS and mental health impacts. Future studies should consider including a wider range of emotional outcomes in their design, not limited to anxiety and depression. Study results may lead to improvements and research in the identification, assessment, and management of PPCS and mental health.

Very preterm brain at rest: longitudinal social-cognitive network connectivity during childhood.

Very preterm (VPT: ≤32 weeks of gestational age) birth poses an increased risk for social and cognitive morbidities that persist throughout life. Resting-state functional network connectivity studies provide information about the intrinsic capacity for cognitive processing. We studied the following four social-cognitive resting-state networks: the default mode, salience, frontal-parietal and language networks. We examined functional connectivity using magnetoencephalography with individual head localization using each participant's MRI at 6 (n = 40) and 8 (n = 40) years of age compared to age- and sex-matched full-term (FT) born children (n = 38 at 6 years and n = 43 at 8 years). VPT children showed increased connectivity compared to FT children in the gamma band (30-80 Hz) at 6 years within the default mode network (DMN), and between the DMN and the salience, frontal-parietal and language networks, pointing to more diffuse, less segregated processing across networks at this age. At 8 years, VPT children had more social and academic difficulties. Increased DMN connectivity at 6 years was associated with social and working memory difficulties at 8 years. Therefore, we suggest that increased DMN connectivity contributes to the observed emerging social and cognitive morbidities in school age.

Exploring sex differences in alpha brain activity as a potential neuromarker associated with neuropathic pain.

ABSTRACT: Alpha oscillatory activity (8-13 Hz) is the dominant rhythm in the awake brain and is known to play an important role in pain states. Previous studies have identified alpha band slowing and increased power in the dynamic pain connectome (DPC) of people with chronic neuropathic pain. However, a link between alpha-band abnormalities and sex differences in brain organization in healthy individuals and those with chronic pain is not known. Here, we used resting-state magnetoencephalography to test the hypothesis that peak alpha frequency (PAF) abnormalities are general features across chronic central and peripheral conditions causing neuropathic pain but exhibit sex-specific differences in networks of the DPC (ascending nociceptive pathway [ANP], default mode network, salience network [SN], and subgenual anterior cingulate cortex). We found that neuropathic pain (N = 25 men and 25 women) was associated with increased PAF power in the DPC compared with 50 age- and sex-matched healthy controls, whereas slower PAF in nodes of the SN (temporoparietal junction) and the ANP (posterior insula) was associated with higher trait pain intensity. In the neuropathic pain group, women exhibited lower PAF power in the subgenual anterior cingulate cortex and faster PAF in the ANP and SN than men. The within-sex analyses indicated that women had neuropathic pain-related increased PAF power in the ANP, SN, and default mode network, whereas men with neuropathic pain had increased PAF power restricted to the ANP. These findings highlight neuropathic pain-related and sex-specific abnormalities in alpha oscillations across the DPC that could underlie aberrant neuronal communication in nociceptive processing and modulation.

A Hidden Markov Model reveals magnetoencephalography spectral frequency-specific abnormalities of brain state power and phase-coupling in neuropathic pain.

Neuronal populations in the brain are engaged in a temporally coordinated manner at rest. Here we show that spontaneous transitions between large-scale resting-state networks are altered in chronic neuropathic pain. We applied an approach based on the Hidden Markov Model to magnetoencephalography data to describe how the brain moves from one activity state to another. This identified 12 fast transient (~80 ms) brain states including the sensorimotor, ascending nociceptive pathway, salience, visual, and default mode networks. Compared to healthy controls, we found that people with neuropathic pain exhibited abnormal alpha power in the right ascending nociceptive pathway state, but higher power and coherence in the sensorimotor network state in the beta band, and shorter time intervals between visits of the sensorimotor network, indicating more active time in this state. Conversely, the neuropathic pain group showed lower coherence and spent less time in the frontal attentional state. Therefore, this study reveals a temporal imbalance and dysregulation of spectral frequency-specific brain microstates in patients with neuropathic pain. These findings can potentially impact the development of a mechanism-based therapeutic approach by identifying brain targets to stimulate using neuromodulation to modify abnormal activity and to restore effective neuronal synchrony between brain states.