Altered Resting-State functional connectivity in the anterior and posterior hippocampus in Post-traumatic stress disorder: The central role of the anterior hippocampus.

BACKGROUND: Post-traumatic stress disorder can be viewed as a memory disorder, with trauma-related flashbacks being a core symptom. Given the central role of the hippocampus in autobiographical memory, surprisingly, there is mixed evidence concerning altered hippocampal functional connectivity in PTSD. We shed light on this discrepancy by considering the distinct roles of the anterior versus posterior hippocampus and examine how this distinction may map onto whole-brain resting-state functional connectivity patterns among those with and without PTSD. METHODS: We first assessed whole-brain between-group differences in the functional connectivity profiles of the anterior and posterior hippocampus within a publicly available data set of resting-state fMRI data from 31 male Vietnam war veterans diagnosed with PTSD (mean age = 67.6 years, sd = 2.3) and 29 age-matched combat-exposed male controls (age = 69.1 years, sd = 3.5). Next, the connectivity patterns of each subject within the PTSD group were correlated with their PTSD symptom scores. Finally, the between-group differences in whole-brain functional connectivity profiles discovered for the anterior and posterior hippocampal seeds were used to prescribe post-hoc ROIs, which were then used to perform ROI-to-ROI functional connectivity and graph-theoretic analyses. RESULTS: The PTSD group showed increased functional connectivity of the anterior hippocampus with affective brain regions (anterior/posterior insula, orbitofrontal cortex, temporal pole) and decreased functional connectivity of the anterior/posterior hippocampus with regions involved in processing bodily self-consciousness (supramarginal gyrus). Notably, decreased anterior hippocampus connectivity with the posterior cingulate cortex/precuneus was associated with increased PTSD symptom severity. The left anterior hippocampus also emerged as a central locus of abnormal functional connectivity, with graph-theoretic measures suggestive of a more central hub-like role for this region in those with PTSD compared to trauma-exposed controls. CONCLUSIONS: Our results highlight that the anterior hippocampus plays a critical role in the neurocircuitry underlying PTSD and underscore the importance of the differential roles of hippocampal sub-regions in serving as biomarkers of PTSD. Future studies should investigate whether the differential patterns of functional connectivity stemming from hippocampal sub-regions is observed in PTSD populations other than older war veterans.

Increased top-down control of emotions during symptom provocation working memory tasks following a RCT of alpha-down neurofeedback in PTSD.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been found to be associated with emotion under-modulation from the prefrontal cortex and a breakdown of the top-down control of cognition and emotion. Novel adjunct therapies such as neurofeedback (NFB) have been shown to normalize aberrant neural circuits that underlie PTSD psychopathology at rest. However, little evidence exists for NFB-linked neural improvements under emotionally relevant cognitive load. The current study sought to address this gap by examining the effects of alpha-down NFB in the context of an emotional n-back task. METHODS: We conducted a 20-week double-blind randomized, sham-controlled trial of alpha-down NFB and collected neuroimaging data before and after the NFB protocol. Participants performed an emotional 1-back and 2-back working memory task, with interleaved trauma-neutral and trauma-relevant cues in the fMRI scanner. Data from 35 participants with a primary diagnosis of PTSD were analyzed in this study (n = 18 in the experimental group undergoing alpha-down NFB, n = 17 in the sham-control group). RESULTS: Firstly, within-group analyses showed clinically significant reductions in PTSD symptom severity scores at the post-intervention timepoint and 3-month follow-up for the experimental group, and not for the sham-control group. The neuroimaging analyses revealed that alpha-down NFB enhanced engagement of top-down cognitive and emotional control centers, such as the dorsolateral prefrontal cortex (dlPFC), and improved integration of the anterior and posterior parts of the default mode network (DMN). Finally, our results also indicate that increased alpha-down NFB performance correlated with increased activity in brain regions involved in top-down control and bodily consciousness/embodied processing of self (TPJ and posterior insula). CONCLUSION: This is the first study to provide mechanistic insights into how NFB may normalize dysfunctional brain activity and connectivity in PTSD under cognitive load with simultaneous symptom provocation, adding to a growing body of evidence supporting the therapeutic neuromodulatory effects of NFB. This preliminary study highlights the benefits of alpha-down NFB training as an adjunctive therapy for PTSD and warrants further investigation into its therapeutic effects on cognitive and emotion control in those with PTSD.

Combined Aerobic Exercise and Neurofeedback Lead to Improved Task-Relevant Intrinsic Network Synchrony.

Lifestyle interventions such as exercise and mindfulness training have the potential to ameliorate mental health symptoms and restore dysregulated intrinsic connectivity network (ICN) dynamics, seen in many psychopathologies. Multiple lifestyle interventions, in combination, may interact synergistically for enhanced benefits. While the impacts of lifestyle interventions on subjective measures of mood are well-documented, their impacts on ICN dynamics are not well-established. In this study, we assessed the validity of EEG-derived measures of ICN dynamics as potential markers of mood disorders, by tracking ICN dynamics and mood symptoms through the course of a longitudinal exercise intervention. Specifically, we investigated the separate and combined effects of aerobic exercise and mindfulness-like neurofeedback training on task-linked ICN dynamics of the default mode network (DMN), central executive network (CEN), and salience network (SN). Participants were assigned pseudo-randomly into four experimental conditions-Control, Running, Neurofeedback, and Combined, performing the corresponding intervention for 16 sessions across 8 weeks. Intervention-linked changes in ICN dynamics were studied using EEG-based neuroimaging scans before and after the 8-week intervention, during which participants performed multiple blocks of autobiographical memory recall (AM) and working memory (WM) trials, designed to activate the DMN and CEN, respectively, and to activate the SN in conjunction with the task-appropriate network. The EEG-based features for classification of the three core networks had been identified in our prior research from simultaneously recorded EEG and fMRI during the same AM and WM tasks. We categorized participants as "responders" or "non-responders" based on whether the exercise intervention increased their aerobic capacity (VO2-max) (Running/Combined group), and/or neurofeedback increased the percentage time spent in the calm mindfulness state (Neurofeedback/Combined group). In responders, compared to each intervention alone, the combined exercise-neurofeedback intervention resulted in a more healthy CEN-SN synchrony pattern. Interestingly, non-responders to neurofeedback exhibited a maladaptive pattern of persistent, task-inappropriate DMN-SN synchrony which we speculate could be linked to depressive rumination. Furthermore, the CEN-SN synchrony at baseline predicted NFB response with up to 80% accuracy, demonstrating the potential utility of such network-based biomarkers in personalizing intervention plans.

Dynamic task-linked switching between brain networks - A tri-network perspective.

The highly influential tri-network model proposed by Menon integrates 3 key intrinsic brain networks - the central executive network (CEN), the salience network (SN), and the default mode network (DMN), into a single cohesive model underlying normal behaviour and cognition. A large body of evidence suggests that abnormal intra- and inter- network connectivity between these three networks underlies the various behavioural and cognitive dysfunctions observed in patients with neuropsychiatric conditions such as PTSD and depression. An important prediction of the tri-network model is that the DMN and CEN networks are anti-correlated under the control of the SN, such that if a task engages one of the two, the SN inhibits the activation of the other. To date most of the evidence surrounding the functions of these three core networks comes from either resting state analyses or in the context of a single task with respect to rest. Few studies have investigated multiple tasks simultaneously or characterized the dynamics of task switching. Hence, a careful investigation of the temporal dynamics of network activity during task switching is warranted. To accomplish this we collected fMRI data from 14 participants that dynamically switched between a 2-back working memory task and an autobiographical memory retrieval task, designed to activate the CEN, DMN and the SN. The fMRI data were used to 1. identify nodes and sub-networks within the three major networks involved in task-linked dynamic network switching, 2. characterize the temporal pattern of activation of these nodes and sub-networks, and finally 3. investigate the causal influence that these nodes and sub-networks exerted on each other. Using a combination of multivariate neuroimaging analyses, timecourse analyses and multivariate Granger causality measures to study the tri-network dynamics, the current study found that the SN co-activates with the task-relevant network, providing a mechanistic insight into SN-mediated network selection in the context of explicit tasks. Our findings also indicate active involvement of the posterior insula and some medial temporal nodes in task-linked functions of the SN and DMN, warranting their inclusion as network nodes in future studies of the tri-network model. These results add to the growing body of evidence showing the complex interplay of CEN, DMN and SN nodes and sub-networks required for adequate task-switching, characterizing a normative pattern of task-linked network dynamics within the context of Menon's tri-network model.

Capturing the Forest but Missing the Trees: Microstates Inadequate for Characterizing Shorter-Scale EEG Dynamics.

The brain is known to be active even when not performing any overt cognitive tasks, and often it engages in involuntary mind wandering. This resting state has been extensively characterized in terms of fMRI-derived brain networks. However, an alternate method has recently gained popularity: EEG microstate analysis. Proponents of microstates postulate that the brain discontinuously switches between four quasi-stable states defined by specific EEG scalp topologies at peaks in the global field potential (GFP). These microstates are thought to be "atoms of thought," involved with visual, auditory, salience, and attention processing. However, this method makes some major assumptions by excluding EEG data outside the GFP peaks and then clustering the EEG scalp topologies at the GFP peaks, assuming that only one microstate is active at any given time. This study explores the evidence surrounding these assumptions by studying the temporal dynamics of microstates and its clustering space using tools from dynamical systems analysis, fractal, and chaos theory to highlight the shortcomings in microstate analysis. The results show evidence of complex and chaotic EEG dynamics outside the GFP peaks, which is being missed by microstate analysis. Furthermore, the winner-takes-all approach of only one microstate being active at a time is found to be inadequate since the dynamic EEG scalp topology does not always resemble that of the assigned microstate, and there is competition among the different microstate classes. Finally, clustering space analysis shows that the four microstates do not cluster into four distinct and separable clusters. Taken collectively, these results show that the discontinuous description of EEG microstates is inadequate when looking at nonstationary short-scale EEG dynamics.

Comparing Tactile to Auditory Guidance for Blind Individuals.

The ability to travel independently is crucial to an individual's quality of life but compromised by visual impairment. Several navigational aids have been developed for blind people to address this limitation. These devices typically employ auditory instructions to guide users to desired waypoints. Unfortunately, auditory instructions may interfere with users' awareness of environmental sounds that signal dangers or provide cues for spatial orientation. Accordingly, there is a need to explore the use of non-auditory modalities to convey information for safe and independent travel. Here, we explored the efficacy of a tactile navigational aid that provides turn signals via vibrations on a hip-worn belt. We compared the performance of 12 blind participants as they navigated a series of paths under the direction of the tactile belt or conventional auditory turn commands; furthermore, we assessed the effect of repeated testing, both in the presence and absence of simulated street sounds. A computer-controlled system triggered each turn command, measured participants' time-to-path-completion, and detected major navigational errors. When participants navigated in a silent environment, they performed somewhat worse with the tactile belt than the auditory device, taking longer to complete each trial and committing more errors. When participants navigated in the presence of simulated street noises, the difference in completion time between auditory and tactile navigation diminished. These results suggest that tactile navigation holds promise as an effective method in everyday environments characterized by ambient noise such as street sounds.