Traumatic Events Are Associated with Diverse Psychological Symptoms in Typically-Developing Children.

Childhood traumatic events are significant risk factors for psychopathology according to adult retrospective research; however, few studies examine trauma exposure and psychological symptoms in pre-adolescent children. Typically-developing children, aged 9-12 years (N = 114), were recruited from the community and selected from the Developmental Chronnecto-Genomics (Dev-CoG) study examining child development. Children completed questionnaires about traumatic life events, posttraumatic stress, anxiety, depression, dissociation, anger, and internalizing and externalizing behaviors. Parents also completed internalizing and externalizing measures. The number of traumatic events significantly correlated with symptom severity across all child-report psychological measures, but surprisingly, trauma was not correlated with any parent-report scores. Follow-up analyses revealed a significant trauma effect for internalizing and externalizing behaviors according to child self-report, but not for parent-report measures. Results indicate that childhood trauma may be a non-specific risk factor for sub-clinical psychopathology in otherwise typically-developing children. Moreover, children appear to be the most appropriate reporters of their own psychological distress.

Attention bias variability and posttraumatic stress symptoms: the mediating role of emotion regulation difficulties.

Growing literature has linked attention bias variability (ABV) to the experience and treatment of posttraumatic stress disorder (PTSD). Unlike assessments of attention bias in only one direction, ABV captures dynamic fluctuations in attention toward and away from threat. While mechanisms underlying the ABV-PTSD relations are unclear, some research implicates emotion regulation difficulties. The current study examined in community women with varying PTSD symptom severity, the amount of variance in the association between ABV and PTSD accounted for by emotion regulation difficulties. The full sample (N = 74) was comprised of 59% community women with PTSD due to domestic and/or sexual violence, and 41% community women without PTSD. All participants completed self-report questionnaires including the Difficulties in Emotion Regulation Scale-16, which assessed emotion regulation. ABV was calculated following a computerised dot probe task. The indirect effect of ABV on PTSD symptom severity through emotion regulation difficulties was statistically significant, while the direct effect between ABV and PTSD symptom severity was not significant. Findings replicated after controlling for total trauma exposure. Clinical implications and literature suggesting how ABV may perpetuate emotion regulation difficulties associated with PTSD symptomology are discussed.

Hippocampal and parahippocampal volumes vary by sex and traumatic life events in children

Background: Childhood trauma is reliably associated with smaller hippocampal volume in adults; however, this finding has not been shown in children, and even less is known about how sex and trauma interact to affect limbic structural development in children. Methods: Typically developing children aged 9 to 15 years who completed a trauma history questionnaire and structural T1-weighted MRI were included in this study (n = 172; 85 female, 87 male). All children who reported 4 or more traumas (n = 36) composed the high trauma group, and all children who reported 3 or fewer traumas (n = 136) composed the low trauma group. Using multivariate analysis of covariance, we compared FreeSurfer-derived structural MRI volumes (normalized by total intracranial volume) of the amygdalar, hippocampal and parahippocampal regions by sex and trauma level, controlling for age and study site. Results: We found a significant sex × trauma interaction, such that girls with high trauma had greater volumes than boys with high trauma. Follow-up analyses indicated significantly increased volumes for girls and generally decreased volumes for boys, specifically in the hippocampal and parahippocampalregions for the high trauma group; we observed no sex differences in the low trauma group. We noted no interaction effect for the amygdalae. Limitations: We assessed a community sample and did not include a clinical sample. We did not collect data about the ages at which children experienced trauma. Conclusion: Results revealed that psychological trauma affects brain development differently in girls and boys. These findings need to be followed longitudinally to elucidate how structural differences progress and contribute to well-known sex disparities in psychopathology.

The developmental trajectory of sensorimotor cortical oscillations.

Numerous studies of motor control have confirmed beta and gamma oscillations in the primary motor cortices during basic movements. These responses include a robust beta decrease that precedes and extends through movement onset, a transient gamma response that coincides with the movement, and a post-movement beta rebound (PMBR) response that occurs after movement offset. While the existence of these responses has been confirmed by many studies, very few studies have examined their developmental trajectory. In the current study, we utilized magnetoencephalography (MEG) to investigate age-related changes in sensorimotor cortical oscillations in a large cross-section of children and adolescents (n = 94; age range = 9 -15 years-old). All participants performed a stimulus detection task with their right finger and the resulting MEG data were examined using oscillatory analysis methods and imaged using a beamformer. Consistent with adult studies, these youth participants exhibited characteristic beta (16-24 Hz) decreases prior to and during movement, as well as PMBR responses following movement offset, and a transient gamma (74-84 Hz) response during movement execution. Our primary findings were that the strength of the PMBR increased with age, while the strength of the gamma synchronization decreased with chronological age. In addition, the strength of each motor-related oscillatory response was significantly correlated with the power of spontaneous activity in the same frequency range and same voxel. This was the case for all three oscillatory responses. In conclusion, we investigated motor-related oscillatory activity in the largest cohort of children and adolescents reported to date, and our results indicated that beta and gamma cortical oscillations continue to develop as children transition into adolescents, and that these responses may not be fully matured until young to middle adulthood.

Neural dynamics of verbal working memory processing in children and adolescents.

Development of cognitive functions and the underlying neurophysiology is evident throughout childhood and adolescence, with higher order processes such as working memory (WM) being some of the last cognitive faculties to fully mature. Previous functional neuroimaging studies of the neurodevelopment of WM have largely focused on overall regional activity levels rather than the temporal dynamics of neural component recruitment. In this study, we used magnetoencephalography (MEG) to examine the neural dynamics of WM in a large cohort of children and adolescents who were performing a high-load, modified verbal Sternberg WM task. Consistent with previous studies in adults, our findings indicated left-lateralized activity throughout the task period, beginning in the occipital cortices and spreading anterior to include temporal and prefrontal cortices during later encoding and into maintenance. During maintenance, the occipital alpha increase that has been widely reported in adults was found to be relatively weak in this developmental sample, suggesting continuing development of this component of neural processing, which was supported by correlational analyses. Intriguingly, we also found sex-specific developmental effects in alpha responses in the right inferior frontal region during encoding and in parietal and occipital cortices during maintenance. These findings suggested a developmental divergence between males and females in the maturation of neural circuitry serving WM during the transition from childhood to adolescence.

tDCS modulates behavioral performance and the neural oscillatory dynamics serving visual selective attention.

Transcranial direct-current stimulation (tDCS) is a noninvasive method for modulating human brain activity. Although there are several hypotheses about the net effects of tDCS on brain function, the field's understanding remains incomplete and this is especially true for neural oscillatory activity during cognitive task performance. In this study, we examined whether different polarities of occipital tDCS differentially alter flanker task performance and the underlying neural dynamics. To this end, 48 healthy adults underwent 20 min of anodal, cathodal, or sham occipital tDCS, and then completed a visual flanker task during high-density magnetoencephalography (MEG). The resulting oscillatory responses were imaged in the time-frequency domain using beamforming, and the effects of tDCS on task-related oscillations and spontaneous neural activity were assessed. The results indicated that anodal tDCS of the occipital cortices inhibited flanker task performance as measured by reaction time, elevated spontaneous activity in the theta (4-7 Hz) and alpha (9-14 Hz) bands in prefrontal and occipital cortices, respectively, and reduced task-related theta oscillatory activity in prefrontal cortices during task performance. Cathodal tDCS of the occipital cortices did not significantly affect behavior or any of these neuronal parameters in any brain region. Lastly, the power of theta oscillations in the prefrontal cortices was inversely correlated with reaction time. In conclusion, anodal tDCS modulated task-related oscillations and spontaneous activity across multiple cortical areas, both near the electrode and in distant sites that were putatively connected to the targeted regions.

Neural dynamics of selective attention deficits in HIV-associated neurocognitive disorder.

OBJECTIVE: To identify the neural markers of attention dysfunction in patients with HIV-associated neurocognitive disorder (HAND). METHODS: Sixty participants, including 40 HIV-infected adults (half with HAND) and 20 demographically matched controls performed a visual selective attention task while undergoing high-density magnetoencephalography. Neuronal activity related to selective attention processing was quantified and compared across the 3 groups, and correlated with neuropsychological measures of attention and executive function. Spontaneous neural activity was also extracted from these attention-related cortical areas and examined with respect to HAND status. RESULTS: HIV-infected participants with and without HAND exhibited behavioral selective attention deficits on the magnetoencephalography task, as indicated by an increased flanker effect. Neuronal measures of flanker interference activity in the alpha and theta range revealed differential dynamics in attention-related brain areas across the 3 groups, especially in those with HAND. In addition, theta range flanker interference activity in the left inferior frontal and dorsolateral prefrontal cortex was associated with executive function and attention composite scores, respectively. Progressively stronger spontaneous alpha and theta activity was also found in unimpaired HIV-infected and HAND participants relative to controls across brain regions implicated in different components of attention processing. CONCLUSIONS: Behavioral and neuronal metrics of selective attention performance distinguish participants with HAND from controls and unimpaired HIV-infected participants. These metrics, along with measures of local spontaneous neural activity, may hold promise as early markers of cognitive decline in participants with HIV infection and be useful prognostic indicators for HAND.

Polarity-dependent modulation of multi-spectral neuronal activity by transcranial direct current stimulation.

The ability to preferentially deploy neural resources to the visual space is an important component of normative cognitive function, however, the population-level cortical dynamics that sub-serve this ability are not fully understood. Specifically, rhythmic activity in the occipital cortices (e.g., theta, alpha, and gamma oscillations) has been strongly implicated in this cognitive process, but these neural responses are difficult to non-invasively manipulate in a systematic manner. In this study, transcranial direct-current stimulation (tDCS) was used to modulate brain activity, while high-density magnetoencephalography (MEG) was employed to quantify changes in rhythm-specific neural activity in the occipital cortices of 57 adults performing a visuospatial processing paradigm. All MEG data was analyzed using advanced source reconstruction and oscillatory analysis methods. Our results indicated that basal levels of occipital alpha activity were increased by an occipital-anodal/supraorbital-cathodal tDCS montage, while basal gamma levels in the same cortices were decreased by tDCS using the same montage with its polarity reversed (occipital-cathodal/supraorbital-anodal). In other words, stimulation with the occipital-anodal montage increased local spontaneous alpha (10-16 Hz) activity, while stimulation with the occipital-cathodal montage selectively decreased local gamma (64-90 Hz) activity. Neither polarity affected stimulus-induced oscillations in the alpha or gamma range. Additionally, these modulations strongly predicted the subsequent formation of fronto-visual functional connectivity within distinct oscillatory rhythms, as well as behavior on the visuospatial discrimination task. These findings provide insight into the multifaceted effects of tDCS on cortical activity, as well as the dynamic oscillatory coding of salient information in the human brain.

Aberrant oscillatory dynamics during somatosensory processing in HIV-infected adults.

While the arrival of combination antiretroviral therapy significantly decreased the prevalence of HIV-associated dementia, between 35 and 70% of all infected adults continue to develop some form of cognitive impairment. These deficits appears to affect multiple neural subsystems, but the mechanisms and extent of damage are not fully understood. In the current study, we utilized magnetoencephalography (MEG), advanced oscillatory analysis methods, and a paired-pulse somatosensory stimulation paradigm to interrogate pre-attentive inhibitory processing in 43 HIV-infected adults and 28 demographically-matched uninfected controls. MEG responses were imaged using a beamformer, and time series data were extracted from the peak voxel in grand-averaged functional brain images to quantify the dynamics of sensory gating, oscillatory power, spontaneous power, and other neural indices. We found a significantly weakened response to the second stimulation compared to the first across groups, indicating significant sensory gating irrespective of HIV-infection. Interestingly, HIV-infected participants exhibited reduced neural responses in the 20-75 Hz gamma range to each somatosensory stimulation compared to uninfected controls, and exhibited significant alterations in peak gamma frequency in response to the second stimulation. Finally, HIV-infected participants also had significantly stronger spontaneous activity in the gamma range (i.e., 20-75 Hz) during the baseline period before stimulation onset. In conclusion, while HIV-infected participants had the capacity to efficiently gate somatosensory input, their overall oscillatory responses were weaker, spontaneous baseline activity was stronger, and their response to the second stimulation had an altered peak gamma frequency. We propose that this pattern of deficits suggests dysfunction in the somatosensory cortices, which is potentially secondary to accelerated aging.

Aberrant occipital dynamics differentiate HIV-infected patients with and without cognitive impairment.

Combination antiretroviral therapies have revolutionized the treatment of HIV infection, and many patients now enjoy a lifespan equal to that of the general population. However, HIV-associated neurocognitive disorders (HAND) remain a major health concern, with between 30% and 70% of all HIV-infected patients developing cognitive impairments during their life time. One important feature of HAND is visuo-perceptual deficits, but the systems-level neural dynamics underlying these impairments are poorly understood. In the current study, we use magnetoencephalography and advanced time series analyses to examine these neural dynamics during a visuospatial processing task in a group of HIV-infected patients without HAND (n = 25), patients with HAND (n = 18), and a group of demographically-matched uninfected controls (n = 24). All participants completed a thorough neuropsychological assessment, and underwent magnetoencephalography and structural MRI protocols. In agreement with previous studies, patients with HAND performed significantly worse than HIV-infected patients without HAND and controls on the cognitive task, in terms of increased reaction time and decreased accuracy. Our magnetoencephalography results demonstrated that both spontaneous and neural oscillatory activity within the occipital cortices were affected by HIV infection, and that these patterns predicted behavioural performance (i.e. accuracy) on the task. Specifically, spontaneous neural activity in the alpha (8-16 Hz) and gamma (52-70 Hz) bands during the prestimulus baseline period, as well as oscillatory theta responses (4-8 Hz) during task performance were aberrant in HIV-infected patients, with both spontaneous alpha and oscillatory theta activity significantly predicting accuracy on the task and neuropsychological performance outside of the magnetoencephalography scanner. Importantly, these rhythmic patterns of population-level neural activity also distinguished patients by HAND status, such that spontaneous alpha activity in patients with HAND was elevated relative to HIV-infected patients without HAND and controls. In contrast, HIV-infected patients with and without HAND had increased spontaneous gamma compared to controls. Finally, there was a stepwise decrease in oscillatory theta activity as a function of disease severity, such that the response diminished from controls to patients without HAND to patients with HAND. Interestingly, the strength of the relationship between this theta response and accuracy also dissociated patient groups in a similar manner (controls > HIV with no HAND > HIV with HAND), indicating a reduced coupling between neurophysiology and behaviour in HIV-infected patients. This study provides the first neuroimaging evidence of a dissociation between HIV-infected patients with and without HAND, and these findings shed new light on the neural bases of cognitive impairment in HIV infection.

The lifespan trajectory of neural oscillatory activity in the motor system.

Numerous studies connect beta oscillations in the motor cortices to volitional movement, and beta is known to be aberrant in multiple movement disorders. However, the dynamic interplay between these beta oscillations, motor performance, and spontaneous beta power (e.g., during rest) in the motor cortices remains unknown. This study utilized magnetoencephalography (MEG) to investigate these three parameters and their lifespan trajectory in 57 healthy participants aged 9-75 years old. Movement-related beta activity was imaged using a beamforming approach, and voxel time series data were extracted from the peak voxels in the primary motor cortices. Our results indicated that spontaneous beta power during rest followed a quadratic lifespan trajectory, while movement-related beta oscillations linearly increased with age. Follow-on analyses showed that spontaneous beta power and the beta minima during movement, together, significantly predicted task performance above and beyond the effects of age. These data are the first to show lifespan trajectories among measures of beta activity in the motor cortices, and suggest that the healthy brain compensates for age-related increases in spontaneous beta activity by increasing the strength of beta oscillations within the motor cortices which, when successful, enables normal motor performance into later life.

tDCS Modulates Visual Gamma Oscillations and Basal Alpha Activity in Occipital Cortices: Evidence from MEG.

Transcranial direct-current stimulation (tDCS) is now a widely used method for modulating the human brain, but the resulting physiological effects are not understood. Recent studies have combined magnetoencephalography (MEG) with simultaneous tDCS to evaluate online changes in occipital alpha and gamma oscillations, but no study to date has quantified the offline (i.e., after tDCS) alterations in these responses. Thirty-five healthy adults received active or sham anodal tDCS to the occipital cortices, and then completed a visual stimulation paradigm during MEG that is known to elicit robust gamma and alpha oscillations. The resulting MEG data were imaged and peak voxel time series were extracted to evaluate tDCS effects. We found that tDCS to the occipital increased the amplitude of local gamma oscillations, and basal alpha levels during the baseline. tDCS was also associated with network-level effects, including increased gamma oscillations in the prefrontal cortex, parietal, and other visual attention regions. Finally, although tDCS did not modulate peak gamma frequency, this variable was inversely correlated with gamma amplitude, which is consistent with a GABA-gamma link. In conclusion, tDCS alters gamma oscillations and basal alpha levels. The net offline effects on gamma activity are consistent with the view that anodal tDCS decreases local GABA.

Transcranial direct-current stimulation modulates offline visual oscillatory activity: A magnetoencephalography study.

Transcranial direct-current stimulation (tDCS) is a noninvasive neuromodulatory method that involves delivering low amplitude, direct current to specific regions of the brain. While a wealth of literature shows changes in behavior and cognition following tDCS administration, the underlying neuronal mechanisms remain largely unknown. Neuroimaging studies have generally used fMRI and shown only limited consensus to date, while the few electrophysiological studies have reported mostly null or counterintuitive findings. The goal of the current investigation was to quantify tDCS-induced alterations in the oscillatory dynamics of visual processing. To this end, we performed either active or sham tDCS using an occipital-frontal electrode configuration, and then recorded magnetoencephalography (MEG) offline during a visual entrainment task. Significant oscillatory responses were imaged in the time-frequency domain using beamforming, and the effects of tDCS on absolute and relative power were assessed. The results indicated significantly increased basal alpha levels in the occipital cortex following anodal tDCS, as well as reduced occipital synchronization at the second harmonic of the stimulus-flicker frequency relative to sham stimulation. In addition, we found reduced power in brain regions near the cathode (e.g., right inferior frontal gyrus [IFG]) following active tDCS, which was absent in the sham group. Taken together, these results suggest that anodal tDCS of the occipital cortices differentially modulates spontaneous and induced activity, and may interfere with the entrainment of neuronal populations by a visual-flicker stimulus. These findings also demonstrate the importance of electrode configuration on whole-brain dynamics, and highlight the deceptively complicated nature of tDCS in the context of neurophysiology.