Sleep-amount differentially affects fear-processing neural circuitry in pediatric anxiety: A preliminary fMRI investigation.

Insufficient sleep, as well as the incidence of anxiety disorders, both peak during adolescence. While both conditions present perturbations in fear-processing-related neurocircuitry, it is unknown whether these neurofunctional alterations directly link anxiety and compromised sleep in adolescents. Fourteen anxious adolescents (AAs) and 19 healthy adolescents (HAs) were compared on a measure of sleep amount and neural responses to negatively valenced faces during fMRI. Group differences in neural response to negative faces emerged in the dorsal anterior cingulate cortex (dACC) and the hippocampus. In both regions, correlation of sleep amount with BOLD activation was positive in AAs, but negative in HAs. Follow-up psychophysiological interaction (PPI) analyses indicated positive connectivity between dACC and dorsomedial prefrontal cortex, and between hippocampus and insula. This connectivity was correlated negatively with sleep amount in AAs, but positively in HAs. In conclusion, the presence of clinical anxiety modulated the effects of sleep-amount on neural reactivity to negative faces differently among this group of adolescents, which may contribute to different clinical significance and outcomes of sleep disturbances in healthy adolescents and patients with anxiety disorders

Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity.

CD38 genetic variation has been associated with autism spectrum disorders and social anxiety disorder, which may result from CD38's regulation of oxytocin secretion. Converging evidence has found that the rs3796863 A-allele contributes to increased social sensitivity compared to the CC genotype. The current study examined the moderating role of CD38 genetic variants (rs3796863 and rs6449182) that have been associated with enhanced (or reduced) social sensitivity on neural activation related to neuroticism, which is commonly elevated in individuals with social anxiety and depression. Adults (n = 72) with varying levels of social anxiety and depression provided biological samples for DNA extraction, completed a measure of neuroticism, and participated in a standardized emotion processing task (affect matching) while undergoing fMRI. A significant interaction effect was found for rs3796863 x neuroticism that predicted right amygdala-subgenual anterior cingulate cortex (sgACC) functional connectivity. Simple slopes analyses showed a positive association between neuroticism and right amygdala-sgACC connectivity among rs3796863 A-allele carriers. Findings suggest that the more socially sensitive rs3796863 A-allele may partially explain the relationship between a known risk factor (i.e. neuroticism) and promising biomarker (i.e. amygdala-sgACC connectivity) in the development and maintenance of social anxiety and depression

Predicting Empathy From Resting State Brain Connectivity: A Multivariate Approach.

Recent task fMRI studies suggest that individual differences in trait empathy and empathic concern are mediated by patterns of connectivity between self-other resonance and top-down control networks that are stable across task demands. An untested implication of this hypothesis is that these stable patterns of connectivity should be visible even in the absence of empathy tasks. Using machine learning, we demonstrate that patterns of resting state fMRI connectivity (i.e. the degree of synchronous BOLD activity across multiple cortical areas in the absence of explicit task demands) of resonance and control networks predict trait empathic concern (n = 58). Empathic concern was also predicted by connectivity patterns within the somatomotor network. These findings further support the role of resonance-control network interactions and of somatomotor function in our vicariously driven concern for others. Furthermore, a practical implication of these results is that it is possible to assess empathic predispositions in individuals without needing to perform conventional empathy assessments

Effect of visual attention on functional connectivity

In our environment, there are so many things to see, e.g., computer screen, buildings, trees and cars in the street. In this busy scenery, we do not process all the information equally, but rather filter out some information and focus more on certain characteristics in the whole scene. In this process, attention plays an important role, and underlying neural correlate is the matter of interest. We focus on investigating how attention changes the connectivity of the fMRI signal in the human brain. Prior studies examined this question, yet most studies used short trial interval (<20s) in examining the connectivity during attention. The short trial interval excludes the slow fMRI fluctuations (<0.1Hz) that showed segmented connectivity structure in the resting-state studies supported by the neurophysiological observations. In the thesis, we introduce an ultra-long trial (2-3mins) to examine connectivity during task conditions, in attention demanding task. In the first study, we asked whether trial length affects the functional connectivity (FC) strength in general during attention task compared to visually matched condition as control. We observed that the long trial interval (2mins) condition showed nearly twice the FC strength compared to short traditional trials (20s). Moreover, attention reorganized the FC as enhanced positive FC between dorsal attention network (DAN) and visual network (VIS) and decreased negative FC between default mode network (DMN) and DAN/VIS, but reduced positive FC within VIS. Notably, the reorganization is frequency dependent: FC changed relied more on slow frequency (0.004-0.05Hz) for the connection between DAN and VIS and high frequency (0.05-0.2Hz) for decorrelation within VIS. In the second study, we addressed the question whether FC strength relies on visual hierarchical distance in visual processing and attention task. We observed a gradient of connectivity, such that DAN connected strongly with high visual region (e.g., V5/MT) that degrades towards lower visual region (e.g., V1). A reversed effect was observed between DMN and VIS, revealing that DMN connected strongly negatively with high visual region that degrades its negative connectivity strength towards lower visual region. More interestingly, we implemented general linear model to the FC strength that showed attention modulates multiplicatively and addictively the connectivity strength along this visual hierarchy. In the third study, we observed how attention changes the connectivity in different features, e.g., color and motion attention. Here, we used seed-to-whole brain connectivity with regressing out the mean signal from the whole brain. First, we observed that V4 and V5/MT selectively connected to the task positive network, including DAN and visual regions, and negatively connected to the DMN. Then, feature-specific analysis showed that color compared to motion attention, selectively connects the V4 to DAN more than V5/MT to DAN, with selective negative connections between V4 and DMN than V5/MT and DMN. This suggest that feature-based attention led the brain communicate specifically cooperative (positive) way, but also competitive (negative) way. Taken together, attention not only reorganizes the connectivity in frequency dependent way, modulates differentially along the visual hierarchy as well as feature-specific manner. More interestingly, our results showed advantages of using long trial block experiment to detect important network connectivity change during attention. Not only applying frequency dependent analysis, but implementation of the GLM in comparing conditions, as well as, regressing out the mean signal from the whole brain for seed-to-whole brain connectivity analysis. All these methods that is used in the thesis can be extended to examine brain connectivity structure noninvasively, that may show important findings in other cognitive tasks, such as decision making or memory tasks

Fractals in the Nervous System: conceptual Implications for Theoretical Neuroscience

This essay is presented with two principal objectives in mind: first, to document the prevalence of fractals at all levels of the nervous system, giving credence to the notion of their functional relevance; and second, to draw attention to the as yet still unresolved issues of the detailed relationships among power law scaling, self-similarity, and self-organized criticality. As regards criticality, I will document that it has become a pivotal reference point in Neurodynamics. Furthermore, I will emphasize the not yet fully appreciated significance of allometric control processes. For dynamic fractals, I will assemble reasons for attributing to them the capacity to adapt task execution to contextual changes across a range of scales. The final Section consists of general reflections on the implications of the reviewed data, and identifies what appear to be issues of fundamental importance for future research in the rapidly evolving topic of this review

Serotonin transporter genotype modulates functional connectivity between amygdala and PCC/PCu during mood recovery

The short (S) allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with increased susceptibility to depression. Previous neuroimaging studies have consistently showed increased amygdala activity during the presentation of negative stimuli or regulation of negative emotion in the homozygous short allele carriers, suggesting the key role of amygdala response in mediating increased risk for depression. The brain default mode network (DMN) has also been shown to modulate amygdala activity. However, it remains unclear whether 5-HTTLPR genetic variation modulates functional connectivity (FC) between the amygdala and regions of DMN. In this study, we re-analyzed our previous imaging dataset and examined the effects of 5-HTTLPR genetic variation on amygdala connectivity. A total of 15 homozygous short (S/S) and 15 homozygous long individuals (L/L) were scanned in functional magnetic resonance imaging (fMRI) during four blocks: baseline, sad mood, mood recovery, and return to baseline. The S/S and L/L groups showed a similar pattern of FC and no differences were found between the two groups during baseline and sad mood scans. However, during mood recovery, the S/S group showed significantly reduced anti-correlation between amygdala and posterior cingulate cortex/precuneus (PCC/PCu) compared to the L/L group. Moreover, PCC/PCu-amygdala connectivity correlated with amygdala activity in the S/S group but not the L/L group. These results suggest that 5-HTTLPR genetic variation modulates amygdala connectivity which subsequently affects its activity during mood regulation, providing an additional mechanism by which the S allele confers depression risk