Rapid dynamics of electrophysiological connectome states are heritable.

Time-varying changes in whole-brain connectivity patterns, or connectome state dynamics, are a prominent feature of brain activity with broad functional implications. While infra-slow (<0.1Hz) connectome dynamics have been extensively studied with fMRI, rapid dynamics highly relevant for cognition are poorly understood. Here, we asked whether rapid electrophysiological connectome dynamics constitute subject-specific brain traits and to what extent they are under genetic influence. Using source-localized EEG connectomes during resting-state (N=928, 473 females), we quantified heritability of multivariate (multi-state) features describing temporal or spatial characteristics of connectome dynamics. States switched rapidly every ~60-500ms. Temporal features were heritable, particularly, Fractional Occupancy (in theta, alpha, beta, and gamma bands) and Transition Probability (in theta, alpha, and gamma bands), representing the duration spent in each state and the frequency of state switches, respectively. Genetic effects explained a substantial proportion of phenotypic variance of these features: Fractional Occupancy in beta (44.3%) and gamma (39.8%) bands and Transition Probability in theta (38.4%), alpha (63.3%), beta (22.6%), and gamma (40%) bands. However, we found no evidence for heritability of spatial features, specifically states' Modularity and connectivity pattern. We conclude that genetic effects strongly shape individuals' connectome dynamics at rapid timescales, specifically states' overall occurrence and sequencing.

Cognitive abilities are associated with rapid dynamics of electrophysiological connectome states.

Time-varying changes in whole-brain connectivity patterns, or connectome state dynamics, hold significant implications for cognition. However, connectome dynamics at fast (> 1Hz) timescales highly relevant to cognition are poorly understood due to the dominance of inherently slow fMRI in connectome studies. Here, we investigated the behavioral significance of rapid electrophysiological connectome dynamics using source-localized EEG connectomes during resting-state (N=926, 473 females). We focused on dynamic connectome features pertinent to individual differences, specifically those with established heritability: Fractional Occupancy (i.e., the overall duration spent in each recurrent connectome state) in beta and gamma bands, and Transition Probability (i.e., the frequency of state switches) in theta, alpha, beta, and gamma bands. Canonical correlation analysis found a significant relationship between the heritable phenotypes of sub-second connectome dynamics and cognition. Specifically, principal components of Transition Probabilities in alpha (followed by theta and gamma bands) and a cognitive factor representing visuospatial processing (followed by verbal and auditory working memory) most notably contributed to the relationship. We conclude that the specific order in which rapid connectome states are sequenced shapes individuals' cognitive abilities and traits. Such sub-second connectome dynamics may inform about behavioral function and dysfunction and serve as endophenotypes for cognitive abilities.

Dynamic trajectories of connectome state transitions are heritable.

The brain's functional connectome is dynamic, constantly reconfiguring in an individual-specific manner. However, which characteristics of such reconfigurations are subject to genetic effects, and to what extent, is largely unknown. Here, we identified heritable dynamic features, quantified their heritability, and determined their association with cognitive phenotypes. In resting-state fMRI, we obtained multivariate features, each describing a temporal or spatial characteristic of connectome dynamics jointly over a set of connectome states. We found strong evidence for heritability of temporal features, particularly, Fractional Occupancy (FO) and Transition Probability (TP), representing the duration spent in each connectivity configuration and the frequency of shifting between configurations, respectively. These effects were robust against methodological choices of number of states and global signal regression. Genetic effects explained a substantial proportion of phenotypic variance of these features (h2=0.39, 95% CI= [.24,.54] for FO; h2=0.43, 95% CI=[.29,.57] for TP). Moreover, these temporal phenotypes were associated with cognitive performance. Contrarily, we found no robust evidence for heritability of spatial features of the dynamic states (i.e., states' Modularity and connectivity pattern). Genetic effects may therefore primarily contribute to how the connectome transitions across states, rather than the precise spatial instantiation of the states in individuals. In sum, genetic effects impact the dynamic trajectory of state transitions (captured by FO and TP), and such temporal features may act as endophenotypes for cognitive abilities.

The Impact of Focused Attention on Emotional Experience: A Functional MRI Investigation.

Emotional well-being depends on the ability to adaptively cope with various emotional challenges. Most studies have investigated the neural mechanisms of emotion regulation strategies deployed relatively later in the timing of processing that leads to full emotional experiences. However, less is known about strategies that are engaged in earlier stages of emotion processing, such as those involving attentional deployment. We investigated the neural mechanisms associated with self-guided Focused Attention (FA) in mitigating subjective negative emotional experiences. Functional magnetic resonance imaging (fMRI) data were recorded while participants viewed a series of composite negative and neutral images with distinguishable foreground (FG) and background (BG) areas. Participants were instructed to focus either on the FG or BG components of the images, and then rated their emotional experiences. Behavioral results showed that FA was successful in decreasing emotional ratings for negative images viewed in BG Focus condition. At the neural level, the BG Focus was associated with increased activity in regions typically implicated in top-down executive control (dorsolateral prefrontal cortex and lateral parietal cortex) and decreased activity in regions linked to affective processing (amygdala and ventrolateral prefrontal cortex). Dissociable brain activity linked to FA also was identified in visual cortices, including between the parahippocampal and fusiform gyri, showing increased versus decreased activity, respectively, during the BG Focus. These findings complement the evidence from prior FA studies with recollected emotional memories as internal stimuli and further demonstrate the effectiveness of self-guided FA in mitigating negative emotional experiences associated with processing of external unpleasant stimuli.

The impact of focused attention on subsequent emotional recollection: A functional MRI investigation.

In his seminal works, Endel Tulving argued that functionally distinct memory systems give rise to subjective experiences of remembering and knowing (i.e., recollection- vs. familiarity-based memory, respectively). Evidence shows that emotion specifically enhances recollection, and this effect is subserved by a synergistic mechanism involving the amygdala (AMY) and hippocampus (HC). In extreme circumstances, however, uncontrolled recollection of highly distressing memories may lead to symptoms of affective disorders. Therefore, it is important to understand the factors that can diminish such detrimental effects. Here, we investigated the effects of Focused Attention (FA) on emotional recollection. FA is an emotion regulation strategy that has been proven quite effective in reducing the impact of emotional responses associated with the recollection of distressing autobiographical memories, but its impact during emotional memory encoding is not known. Functional MRI and eye-tracking data were recorded while participants viewed a series of composite negative and neutral images with distinguishable foreground (FG) and background (BG) areas. Participants were instructed to focus either on the FG or BG content of the images and to rate their emotional responses. About 4 days later, participants' memory was assessed using the R/K procedure, to indicate whether they Recollected specific contextual details about the encoded images or the images were just familiar to them - i.e., participants only Knew that they saw the pictures without being able to remember specific contextual details. First, results revealed that FA was successful in decreasing memory for emotional pictures viewed in BG Focus condition, and this effect was driven by recollection-based retrieval. Second, the BG Focus condition was associated with decreased activity in the AMY, HC, and anterior parahippocampal gyrus for subsequently recollected emotional items. Moreover, correlation analyses also showed that reduced activity in these regions predicted greater reduction in emotional recollection following FA. These results demonstrate the effectiveness of FA in mitigating emotional experiences and emotional recollection associated with unpleasant emotional events.

Structural and Resting-State Brain Alterations in Trauma-Exposed Firefighters: Preliminary Results.

Purpose: To analyze the altered brain regions and intrinsic brain activity patterns in trauma-exposed firefighters without posttraumatic stress disorder (PTSD). Materials and Methods: Resting-state functional MRI (rsfMRI) was performed for all subjects. Thirty-one firefighters over 40 years of age without PTSD (31 men; mean age, 49.8 ± 4.7 years) were included. Twenty-six non-traumatized healthy controls (HCs) (26 men; mean age, 65.3 ± 7.84 years) were also included. Voxel-based morphometry was performed to investigate focal differences in the brain anatomy. Seed-based functional connectivity analysis was performed to investigate differences in spontaneous brain characteristics. Results: The mean z-scores of the Seoul Verbal Learning Test for immediate and delayed recall, Controlled Oral Word Association Test (COWAT) score for animals, and COWAT phonemic fluency were significantly lower in the firefighter group than in the HCs, indicating decreased neurocognitive function. Compared to HCs, firefighters showed reduced gray matter volume in the left superior parietal gyrus and left inferior temporal gyrus. Further, in contrast to HCs, firefighters showed alterations in rsfMRI values in multiple regions, including the fusiform gyrus and cerebellum. Conclusion: Structural and resting-state functional abnormalities in the brain may be useful imaging biomarkers for identifying alterations in trauma-exposed firefighters without PTSD.

Dysautonomia is associated with structural and functional alterations in Parkinson disease.

OBJECTIVE: To investigate whether the presence of autonomic dysfunction is associated with white matter and functional connectivities and the level of cognitive performance in patients with de novo Parkinson disease (PD). METHODS: Seventy-five patients with de novo PD underwent a comprehensive autonomic function test and were classified into 2 groups according to the Composite Autonomic Severity Score (CASS; 30 with moderate to severe autonomic dysfunction [CASS 4-10, PD-AUT+] and 45 without significant autonomic dysfunction [CASS 0-3, PD-AUT-]). Network-based statistics and a graph theoretical analysis were performed to assess the interregional white matter connectivity using diffusion tensor imaging. We also performed analyses of resting-state functional connectivity and compared cognitive performance between the 2 groups. RESULTS: There were no significant differences in demographic characteristics and vascular risk factors between the PD-AUT+ and PD-AUT- groups. The PD-AUT+ group showed poorer cognitive performance on frontal/executive function than the PD-AUT- group. The PD-AUT+ group exhibited severely disrupted white matter connectivity in both fronto-subcortical and posterior cortical regions, which was well correlated with the severity of autonomic dysfunction assessed by the CASS. In addition, functional connectivity within the executive control network and dorsal attention network negatively correlated with the CASS. CONCLUSIONS: Our results suggest that autonomic dysfunction is associated with disrupted white matter and functional brain connectivity as well as cognitive impairment in de novo patients with PD.

Characteristics of Resting-State Functional Connectivity in HIV-Associated Neurocognitive Disorder.

BACKGROUND: HIV-associated neurocognitive disorder (HAND) can occur in patients without prior AIDS defining illness and can be debilitating. This study aimed to evaluate the difference in the patterns of intrinsic brain activity between patients with or without HAND for deepening our understanding of HAND. METHODS: We evaluated 24 HIV-infected individuals, 12 with previously diagnosed HAND and 12 previously diagnosed without HAND, and 11 seronegative individuals. These individuals then underwent repeat NP testing and a functional brain MRI scan. For functional MRI analysis, seed-based analysis with bilateral precuneus cortex seed was applied. RESULTS: Among the 12 individuals with previously diagnosed HAND, 3 showed improvement of their neurocognitive function and 1 was excluded for worsening liver disease. Among the 12 patients who previously had normal neurocognitive function, 2 showed neurocognitive impairment. Overall, the HAND group, who had impaired cognitive function at the time of MRI scan, showed significant decrease of resting status functional connectivity between bilateral precuneus and prefrontal cortex (PFC) compared with nonHAND group, those who had normal neurocognitive function (Corrected P<0.05). The functional connectivity with the right inferior frontal operculum and right superior frontal gyrus was positively correlated with memory and learning ability. CONCLUSIONS: This cross-sectional study found a significant difference in fMRI patterns between patients with and without HAND. Decreased functional connectivity between precuneus and PFC could be possible functional substrate for cognitive dysfunction in HIV patients, which should be characterized in a longitudinal study.