Altered long-range functional connectivity in PTSD: Role of the infraslow oscillations of cortical activity amplitude envelopes.

OBJECTIVE: Coupling between the amplitude envelopes (AEs) of regional cortical activity reflects mechanisms that coordinate the excitability of large-scale cortical networks. We used resting-state MEG recordings to investigate the association between alterations in the coupling of cortical AEs and symptoms of post-traumatic stress disorder (PTSD). METHODS: Participants (n = 96) were service members with combat exposure and various levels of post-traumatic stress severity (PTSS). We assessed the correlation between PTSS and (1) coupling of broadband cortical AEs of beta band activity, (2) coupling of the low- (<0.5 Hz) and high-frequency (>0.5 Hz) components of the AEs, and (3) their time-varying patterns. RESULTS: PTSS was associated with widespread hypoconnectivity assessed from the broadband AE fluctuations, which correlated with subscores for the negative thoughts and feelings/emotional numbing (NTF/EN) and hyperarousal clusters of symptoms. Higher NTF/EN scores were also associated with smaller increases in resting-state functional connectivity (rsFC) with time during the recordings. The distinct patterns of rsFC in PTSD were primarily due to differences in the coupling of low-frequency (infraslow) fluctuations of the AEs of beta band activity. CONCLUSIONS: Our findings implicate the mechanisms underlying the regulation/coupling of infraslow oscillations in the alterations of rsFC assessed from broadband AEs and in PTSD symptomatology. SIGNIFICANCE: Altered coordination of infraslow amplitude fluctuations across large-scale cortical networks can contribute to network dysfunction and may provide a target for treatment in PTSD.

Cognitive flexibility in post-traumatic stress disorder: Sustained interference associated with altered modulation of cortical oscillatory activity during task-switching.

Post-traumatic stress disorder (PTSD) is associated with deficits in cognitive flexibility, with evidence suggesting that these deficits may be a risk factor for the development of core PTSD symptoms. Understanding the neurophysiological substrate of this association could aid the development of effective therapies for PTSD. In this study, we investigated the relationship between post-traumatic stress severity (PTSS) in service members with combat exposure and the modulation of cortical oscillatory activity during a test of cognitive flexibility. Participants were assigned to three groups based on PTSS scores: low (well below a threshold consistent with a diagnosis of PTSD, n = 30), moderate (n = 32), and high (n = 29) symptom severity. Magnetoencephalography data were recorded while participants performed a cued rule-switching task in which two matching rules were repeated or switched across consecutive trials. Participants with high PTSS had longer reaction times for both switch and repeat trials, and showed evidence of sustained residual interference during repeat trials. During the cue-stimulus interval, participants with moderate and high PTSS showed higher relative theta power in switch trials over left dorsolateral prefrontal cortex (DLPFC). After test-stimulus onset, participants with high PTSS showed less suppression of beta band activity, which was present over multiple prefrontal, parietal, and temporal regions in switch trials, but it was confined to ventromedial prefrontal cortex in repeat trials. Higher theta band activity is a marker of effortful voluntary shifting of attention, while lower suppression of beta band activity reflects difficulties with inhibition of competing perceptual information and courses of action. These findings are consistent with a role for altered suppression of beta band activity, which can be due to less effective top-down bias signals exerted by DLPFC, in the etiology of cognitive flexibility deficits in PTSD.

Post-traumatic stress disorder is associated with alterations in evoked cortical activation during visual recognition of scenes.

We recorded magnetoencephalography data during a visual recognition task in participants with combat exposure (n = 40, age: 41.2 ± 7.2 years) to investigate the relationship between the evoked brain activity, behavioral performance, and the severity of their post-traumatic stress symptoms assessed using the PTSD Check List for DSM V version (PCL-5). In an initial study session, participants were presented with a series of images of outdoor scenes and were instructed to study the images for an upcoming recognition test. In a subsequent session, the original images were shown intermixed with novel images while participants performed the recognition task. PCL-5 scores were negatively correlated with discrimination performance and with the recognition accuracy for original images. During the recognition session, higher PCL-5 scores were associated with reduced relative power of the evoked response to original images from 100 ms to 300 ms following the image onset over a distributed brain network including the bilateral inferior frontal gyri, left middle frontal gyrus, left supramarginal gyrus, right precuneus and the bilateral superior temporal gyri. These findings indicate that the lower recognition performance in participants with higher PTSD symptom severity is associated with altered cortical activity in brain regions that are known to play a role in the elaboration on visual cues that supports recollection.

Altered modulation of beta band oscillations during memory encoding is predictive of lower subsequent recognition performance in post-traumatic stress disorder.

We studied the relationship between electrophysiological markers of memory encoding, subsequent recognition performance, and severity of PTSD symptoms in service members with combat exposure (n = 40, age: 41.2 ± 7.2 years) and various levels of PTSD symptom severity assessed using the PTSD Check List for DSM V version (PCL-5). Brain activity was recorded using magnetoencephalography during a serial presentation of 86 images of outdoor scenes that were studied by participants for an upcoming recognition test. In a second session, the original images were shown intermixed with an equal number of novel images while participants performed the recognition task. Participants recognized 76.0% ± 12.1% of the original images and correctly categorized as novel 89.9% ± 7.0% of the novel images. A negative correlation was present between PCL-5 scores and discrimination performance (Spearman rs = -0.38, p = 0.016). PCL-5 scores were also negatively correlated with the recognition accuracy for original images (rs = -0.37, p = 0.02). Increases in theta and gamma power and decreases in alpha and beta power were observed over distributed brain networks during memory encoding. Higher PCL-5 scores were associated with less suppression of beta band power in bilateral ventral and medial temporal regions and in the left orbitofrontal cortex. These regions also showed positive correlations between the magnitude of suppression of beta power during encoding and subsequent recognition accuracy. These findings indicate that the lower recognition performance in participants with greater PTSD symptom severity may be due in part to ineffective encoding reflected in altered modulation of beta band oscillatory activity.

Post-traumatic stress disorder is associated with altered modulation of prefrontal alpha band oscillations during working memory.

OBJECTIVE: To investigate the relationship between the severity of PTSD symptoms, modulation of alpha band oscillations, and behavioral performance in a working memory task. METHODS: Magnetoencephalography data were recorded in 35 participants with combat exposure and various degrees of PTSD symptom severity while they performed a modified Sternberg working memory task: briefly presented sets of two or six letters had to be held in memory and participants indicated whether subsequent probe letters were present or absent from these sets. RESULTS: PTSD scores were positively correlated with the false positive rate in the high memory load condition. Higher rates of false recognition were associated with negative probes that were seen in recent previous trials (negative probe recency effect) or were physically similar with the list letters. The relative alpha band power in the left middle frontal gyrus was negatively correlated with both PTSD scores and false positive rates. CONCLUSIONS: Reduced task specific modulation of alpha band oscillations in left middle frontal cortex may reflect alterations in the functions of pattern separation and suppression of memory traces for irrelevant or no longer relevant information in PTSD. SIGNIFICANCE: The lower amplitude of prefrontal alpha band oscillations may represent an important physiological basis for core PTSD symptoms and can provide a target for interventions to augment response to treatment.

Activation of dominant hemisphere association cortex during naming as a function of cognitive performance in mild traumatic brain injury: Insights into mechanisms of lexical access.

Patients with a history of mild traumatic brain injury (mTBI) and objective cognitive deficits frequently experience word finding difficulties in normal conversation. We sought to improve our understanding of this phenomenon by determining if the scores on standardized cognitive testing are correlated with measures of brain activity evoked in a word retrieval task (confrontational picture naming). The study participants (n = 57) were military service members with a history of mTBI. The General Memory Index (GMI) determined after administration of the Rivermead Behavioral Memory Test, Third Edition, was used to assign subjects to three groups: low cognitive performance (Group 1: GMI ≤ 87, n = 18), intermediate cognitive performance (Group 2: 88 ≤ GMI ≤ 99, n = 18), and high cognitive performance (Group 3: GMI ≥ 100, n = 21). Magnetoencephalography data were recorded while participants named eighty pictures of common objects. Group differences in evoked cortical activity were observed relatively early (within 200 ms from picture onset) over a distributed network of left hemisphere cortical regions including the fusiform gyrus, the entorhinal and parahippocampal cortex, the supramarginal gyrus and posterior part of the superior temporal gyrus, and the inferior frontal and rostral middle frontal gyri. Differences were also present in bilateral cingulate cortex and paracentral lobule, and in the right fusiform gyrus. All differences reflected a lower amplitude of the evoked responses for Group 1 relative to Groups 2 and 3. These findings may indicate weak afferent inputs to and within an extended cortical network including association cortex of the dominant hemisphere in patients with low cognitive performance. The association between word finding difficulties and low cognitive performance may therefore be the result of a diffuse pathophysiological process affecting distributed neuronal networks serving a wide range of cognitive processes. These findings also provide support for a parallel processing model of lexical access.

Reduced prefrontal MEG alpha-band power in mild traumatic brain injury with associated posttraumatic stress disorder symptoms.

OBJECTIVE: To determine if changes in cortical alpha-band power in patients with mild traumatic brain injury (mTBI) are associated with the severity of their post-traumatic stress disorder (PTSD) symptoms, and if injury severity and level of exposure to psychologically traumatic events are predictors of these electrophysiological changes. METHODS: Resting-state magnetoencephalographic recordings were analyzed in 32 patients with mTBI. Alpha-band power was estimated for each patient in 68 cortical regions and was compared between groups of patients with low versus high PTSD symptoms severity. RESULTS: Participants with high PTSD symptom severity showed reduced alpha-band power bilaterally in the superior and middle frontal gyri and frontal poles, and in the left inferior frontal gyrus. Alpha-band power in bilateral middle frontal gyri and frontal poles was negatively correlated with scores reflecting symptoms of emotional numbing. Loss of consciousness (LOC) associated with mTBI and level of exposure to psychologically traumatic events were predictors of decreased prefrontal alpha-band power in some of these regions. CONCLUSION: Altered prefrontal alpha-band activity, shown to be partly explained by mTBI-related LOC, is associated with PTSD symptoms severity. SIGNIFICANCE: Our findings will guide future studies addressing the electrophysiological mechanisms underlying a higher incidence of PTSD in patients with mTBI.

Adaptive changes in the neuromagnetic response of the primary and association somatosensory areas following repetitive tactile hand stimulation in humans.

Cortical adaptation in the primary somatosensory cortex (SI) has been probed using different stimulation modalities and recording techniques, in both human and animal studies. In contrast, considerably less knowledge has been gained about the adaptation profiles in other areas of the cortical somatosensory network. Using magnetoencephalography (MEG), we examined the patterns of short-term adaptation for evoked responses in SI and somatosensory association areas during tactile stimulation applied to the glabrous skin of the hand. Cutaneous stimuli were delivered as trains of serial pulses with a constant frequency of 2 Hz and 4 Hz in separate runs, and a constant inter-train interval of 5 s. The unilateral stimuli elicited transient responses to the serial pulses in the train, with several response components that were separated by independent component analysis. Subsequent source reconstruction techniques identified regional generators in the contralateral SI and somatosensory association areas in the posterior parietal cortex (PPC). Activity in the bilateral secondary somatosensory cortex (i.e., SII/PV) was also identified, although less consistently across subjects. The dynamics of the evoked activity in each area and the frequency-dependent adaptation effects were assessed from the changes in the relative amplitude of serial responses in each train. We show that the adaptation profiles in SI and PPC areas can be quantitatively characterized from neuromagnetic recordings using tactile stimulation, with the sensitivity to repetitive stimulation increasing from SI to PPC. A similar approach for SII/PV has proven less straightforward, potentially due to the tendency of these areas to respond selectively to certain stimuli.

The effect of volume conductor modeling on the estimation of cardiac vectors in fetal magnetocardiography.

Previous studies based on fetal magnetocardiographic (fMCG) recordings used simplified volume conductor models to estimate the fetal cardiac vector as an unequivocal measure of the cardiac source strength. However, the effect of simplified volume conductor modeling on the accuracy of the fMCG inverse solution remains largely unknown. Aiming to determine the sensitivity of the source estimators to the details of the volume conductor model, we performed simulations using fetal-maternal anatomical information from ultrasound images obtained in 20 pregnant women in various stages of pregnancy. The magnetic field produced by a cardiac source model was computed using the boundary-element method for a piecewise homogeneous volume conductor with three nested compartments (fetal body, amniotic fluid and maternal abdomen) of different electrical conductivities. For late gestation, we also considered the case of a fourth highly insulating layer of vernix caseosa covering the fetus. The errors introduced for simplified volume conductors were assessed by comparing the reconstruction results obtained with realistic versus spherically symmetric models. Our study demonstrates the significant effect of simplified volume conductor modeling, resulting mainly in an underestimation of the cardiac vector magnitude and low goodness-of-fit. These findings are confirmed by the analysis of real fMCG data recorded in mid-gestation.

Cutaneous stimulation of the digits and lips evokes responses with different adaptation patterns in primary somatosensory cortex.

Neuromagnetic evoked fields were recorded to compare the adaptation of the primary somatosensory cortex (SI) response to tactile stimuli delivered to the glabrous skin at the fingertips of the first three digits (condition 1) and between midline upper and lower lips (condition 2). The stimulation paradigm allowed to characterize the response adaptation in the presence of functional integration of tactile stimuli from adjacent skin areas in each condition. At each stimulation site, cutaneous stimuli (50 ms duration) were delivered in three runs, using trains of 6 pulses with regular stimulus onset asynchrony (SOA). The pulses were separated by SOAs of 500 ms, 250 ms or 125 ms in each run, respectively, while the inter-train interval was fixed (5s) across runs. The evoked activity in SI (contralateral to the stimulated hand, and bilaterally for lips stimulation) was characterized from the best-fit dipoles of the response component peaking around 70 ms for the hand stimulation, and 8 ms earlier (on average) for the lips stimulation. The SOA-dependent long-term adaptation effects were assessed from the change in the amplitude of the responses to the first stimulus in each train. The short-term adaptation was characterized by the lifetime of an exponentially saturating model function fitted to the set of suppression ratios of the second relative to the first SI response in each train. Our results indicate: 1) the presence of a rate-dependent long-term adaptation effect induced only by the tactile stimulation of the digits; and 2) shorter recovery lifetimes for the digits compared with the lips stimulation.

N400 responses of children with primary language disorder: intervention effects.

Event-related brain potentials were examined in 6 to 8-year-old children with primary language disorder before and after a 5-week narrative-based language intervention. Participants listened to sentences ending with semantically congruous or incongruous words. By comparison with typical controls, the children with primary language disorder exhibited no pretreatment differences in their N400 responses to congruous and incongruous sentence-final words. After intervention, the typical incongruous-congruous difference was observable owing to a dramatic reduction in the amplitude of the N400 response to congruous words. These characteristic changes in brain responses may reflect a positive effect of the language intervention on the lexical-semantic processing skills in children with language impairment.

Spatio-temporal reconstruction of bilateral auditory steady-state responses using MEG beamformers.

A rapidly growing number of neuromagnetic studies focus on the analysis of auditory steady-state responses (ASSR) in relation to a diverse array of factors including age, selective attention, and presence of psychopathology. The objectives of these studies require accurate spatio-temporal estimation of the underlying neural generators, a challenging task due to the relatively low signal strength and high correlation between bilateral auditory cortical sources. This paper evaluates the performance of two beamforming schemes that can potentially overcome such difficulties: 1) the linearly constrained minimum variance beamformer with partial sensor coverage (LCMV-PSC), and 2) the multiple constrained minimum-variance beamformer with coherent source region suppression (MCMV-CSRS). Simulation experiments are conducted to assess the impact of source parameters on the reconstruction accuracy. The results indicate that the LCMV-PSC method is prone to localization errors that essentially occur along medio-lateral directions, increase with source depth, and are associated to amplitude and phase distortions of the estimated time courses of activity. Comparatively, the MCMV-CSRS method exhibits precise localization and minimal amplitude and phase distortion for a broad range of relative interferer's positions within the suppression region. The results from the numerical experiments are validated on real magnetoencephalographic (MEG) data collected from a 40-Hz ASSR paradigm.

Reconstruction of fetal cardiac vectors from multichannel fMCG data using recursively applied and projected multiple signal classification.

Previous attempts at unequivocal specification of signal strength in fetal magnetocardiographic (fMCG) recordings have used an equivalent current dipole (ECD) to estimate the cardiac vector at the peak of the averaged QRS complex. However, even though the magnitude of fetal cardiac currents are anticipated to be relatively stable, ECD-based estimates of signal strength show substantial and unrealistic variation when comparing results from different time windows of the same recording session. The present study highlights the limitations of the ECD model, and proposes a new methodology for fetal cardiac source reconstruction. The proposed strategy relies on recursive subspace projections to estimate multiple dipoles that account for the distributed myocardial currents. The dipoles are reconstructed from spatio-temporal fMCG data, and are subsequently used to derive estimators of the cardiac vector over the entire QRS. The new method is evaluated with respect to simulated data derived from a model of ventricular depolarization, which was designed to account for the complexity of the fetal cardiac source configuration on the QRS interval. The results show that the present methodology overcomes the drawbacks of conventional ECD fitting, by providing robust estimators of the cardiac vector. Additional evaluation with real fMCG data show fetal cardiac vectors whose morphology closely resembles that obtained in adult MCG.