Performing group-level functional image analyses based on homologous functional regions mapped in individuals

Functional MRI (fMRI) studies have traditionally relied on intersubject normalization based on global brain morphology, which cannot establish proper functional correspondence between subjects due to substantial intersubject variability in functional organization. Here, we reliably identified a set of discrete, homologous functional regions in individuals to improve intersubject alignment of fMRI data. These functional regions demonstrated marked intersubject variability in size, position, and connectivity. We found that previously reported intersubject variability in functional connectivity maps could be partially explained by variability in size and position of the functional regions. Importantly, individual differences in network topography are associated with individual differences in task-evoked activations, suggesting that these individually specified regions may serve as the localizer to improve the alignment of task-fMRI data. We demonstrated that aligning task-fMRI data using the regions derived from resting state fMRI may lead to increased statistical power of task-fMRI analyses. In addition, resting state functional connectivity among these homologous regions is able to capture the idiosyncrasies of subjects and better predict fluid intelligence (gF) than connectivity measures derived from group-level brain atlases. Critically, we showed that not only the connectivity but also the size and position of functional regions are related to human behavior. Collectively, these findings suggest that identifying homologous functional regions across individuals can benefit a wide range of studies in the investigation of connectivity, task activation, and brain-behavior associations. Author summary No two individuals are alike. The size, shape, position, and connectivity patterns of brain functional regions can vary drastically between individuals. While interindividual differences in functional organization are well recognized, to date, standard procedures for functional neuroimaging research still rely on aligning different subjects' data to a nominal average brain based on global brain morphology. We developed an approach to reliably identify homologous functional regions in each individual and demonstrated that aligning data based on these homologous functional regions can significantly improve the study of resting state functional connectivity, task-fMRI activations, and brain-behavior associations. Moreover, we showed that individual differences in size, position, and connectivity of brain functional regions are dissociable, and each can provide nonredundant information in explaining human behavior

Anxiety Shapes Amygdala-Prefrontal Dynamics During Movie Watching

Background: A well-characterized amygdala–dorsomedial prefrontal circuit is thought to be crucial for threat vigilance during anxiety. However, engagement of this circuitry within relatively naturalistic paradigms remains unresolved. // Methods: Using an open functional magnetic resonance imaging dataset (Cambridge Centre for Ageing Neuroscience; n = 630), we sought to investigate whether anxiety correlates with dynamic connectivity between the amygdala and dorsomedial prefrontal cortex during movie watching. // Results: Using an intersubject representational similarity approach, we saw no effect of anxiety when comparing pairwise similarities of dynamic connectivity across the entire movie. However, preregistered analyses demonstrated a relationship between anxiety, amygdala-prefrontal dynamics, and anxiogenic features of the movie (canonical suspense ratings). Our results indicated that amygdala-prefrontal circuitry was modulated by suspense in low-anxiety individuals but was less sensitive to suspense in high-anxiety individuals. We suggest that this could also be related to slowed habituation or amplified anticipation. Moreover, a measure of threat-relevant attentional bias (accuracy/reaction time to fearful faces) demonstrated an association with connectivity and suspense. // Conclusions: Overall, this study demonstrated the presence of anxiety-relevant differences in connectivity during movie watching, varying with anxiogenic features of the movie. Mechanistically, exactly how and when these differences arise remains an opportunity for future research

Using Movies to Probe the Neurobiology of Anxiety

Over the past century, research has helped us build a fundamental understanding of the neurobiological underpinnings of anxiety. Specifically, anxiety engages a broad range of cortico-subcortical neural circuitry. Core to this is a ‘defensive response network’ which includes an amygdala-prefrontal circuit that is hypothesized to drive attentional amplification of threat-relevant stimuli in the environment. In order to help prepare the body for defensive behaviors to threat, anxiety also engages peripheral physiological systems. However, our theoretical frameworks of the neurobiology of anxiety are built mostly on the foundations of tightly-controlled experiments, such as task-based fMRI. Whether these findings generalize to more naturalistic settings is unknown. To address this shortcoming, movie-watching paradigms offer an effective tool at the intersection of tightly controlled and entirely naturalistic experiments. Particularly, using suspenseful movies presents a novel and effective means to induce and study anxiety. In this thesis, I demonstrate the potential of movie-watching paradigms in the study of how trait and state anxiety impact the ‘defensive response network’ in the brain, as well as peripheral physiology. The key findings reveal that trait anxiety is associated with differing amygdala-prefrontal responses to suspenseful movies; specific trait anxiety symptoms are linked to altered states of anxiety during suspenseful movies; and states of anxiety during movies impact brain-body communication. Notably, my results frequently diverged from those of conventional task-based experiments. Taken together, the insights gathered from this thesis underscore the utility of movie-watching paradigms for a more nuanced understanding of how anxiety impacts the brain and peripheral physiology. These outcomes provide compelling evidence that further integration of naturalistic methods will be beneficial in the study of the neurobiology of anxiety

Mindfulness Training to Enhance Emotion Regulation in a Polarizing Political Context: A Multimethod Investigation

The U.S. continues to show an upward trend in political polarization, perceived as a moral divide between liberal and conservative ideological groups. This moralization of political identity has contributed to the escalation of negative emotions (e.g., fear, anger, and hatred) directed towards political outgroup members. Although negative emotions are potent motivators of political intolerance, these emotions are nevertheless subject to regulation. Mindfulness offers a promising yet understudied emotion regulation strategy which may facilitate open receptivity towards opposing partisans. The present randomized controlled trial (RCT) examines the effects of short-term mindfulness training (MT) vs structurally equivalent Cognitive Reappraisal training (CT) on the regulation of political intergroup negative affect using an ecologically-situated naturalistic neuorimaging paradigm. Functional near-infrared spectroscopy (fNIRS) neural synchrony effects coupled with emotion reactivity ratings reveal an ostensible pathway for the mindful regulation of negative intergroup emotion

ADHD desynchronizes brain activity during watching a distracted multi-talker conversation

Individuals with attention-deficit/hyperactivity disorder (ADHD) have difficulties navigating dynamic everyday situations that contain multiple sensory inputs that need to either be attended to or ignored. As conventional experimental tasks lack this type of everyday complexity, we administered a film-based multi-talker condition with auditory distractors in the background. ADHD-related aberrant brain responses to this naturalistic stimulus were identified using intersubject correlations (ISCs) in functional magnetic resonance imaging (fMRI) data collected from 51 adults with ADHD and 29 healthy controls. A novel permutation-based approach introducing studentized statistics and subject-wise voxel-level null-distributions revealed that several areas in cerebral attention networks and sensory cortices were desynchronized in participants with ADHD (n = 20) relative to healthy controls (n = 20). Specifically, desynchronization of the posterior parietal cortex occurred when irrelevant speech or music was presented in the background, but not when irrelevant white noise was presented, or when there were no distractors. We also show regionally distinct ISC signatures for inattention and impulsivity. Finally, post-scan recall of the film contents was associated with stronger ISCs in the default-mode network for the ADHD and in the dorsal attention network for healthy controls. The present study shows that ISCs can further our understanding of how a complex environment influences brain states in ADHD.Peer reviewe

Representation of social content in dorsomedial prefrontal cortex underlies individual differences in agreeableness trait

Personality traits reflect key aspects of individual variability in different psychological domains. Understanding the mechanisms that give rise to these differences requires an exhaustive investigation of the behaviors associated with such traits, and their underlying neural sources. Here we investigated the mechanisms underlying agreeableness, one of the five major dimensions of personality, which has been linked mainly to socio-cognitive functions. In particular, we examined whether individual differences in the neural representations of social information are related to differences in agreeableness of individuals. To this end, we adopted a multivariate representational similarity approach that captured within single individuals the activation pattern similarity of social and non-social content, and tested its relation to the agreeableness trait in a hypothesis-driven manner. The main result confirmed our prediction: processing social and non-social content led to similar patterns of activation in individuals with low agreeableness, while in more agreeable individuals these patterns were more dissimilar. Critically, this association between agreeableness and encoding similarity of social and random content was significant only in the dorsomedial prefrontal cortex, a brain region consistently involved during attributions of mental states. The present finding reveals the link between neural mechanisms underlying social information processing and agreeableness, a personality trait highly related to socio-cognitive abilities, thereby providing a step forward in characterizing its neural determinants. Furthermore, it emphasizes the advantage of multivariate pattern analysis approaches in capturing and understanding the neural sources of individual variations

Disentangling cortical functional connectivity strength and topography reveals divergent roles of genes and environment

The human brain varies across individuals in its morphology, function, and cognitive capacities. Variability is particularly high in phylogenetically modern regions associated with higher order cognitive abilities, but its relationship to the layout and strength of functional networks is poorly understood. In this study we disentangled the variability of two key aspects of functional connectivity: strength and topography. We then compared the genetic and environmental influences on these two features. Genetic contribution is heterogeneously distributed across the cortex and differs for strength and topography. In heteromodal areas genes predominantly affect the topography of networks, while their connectivity strength is shaped primarily by random environmental influence such as learning. We identified peak areas of genetic control of topography overlapping with parts of the processing stream from primary areas to network hubs in the default mode network, suggesting the coordination of spatial configurations across those processing pathways. These findings provide a detailed map of the diverse contribution of heritability and individual experience to the strength and topography of functional brain architecture.Nanyang Technological UniversityPublished versionThis work was supported by the Medical University of Vienna, the Austrian Research Fund (FWF) [grants P 35189, P 34198, and I 3925-B27] in collaboration with the French National Research Agency (ANR), the Vienna Science and Technology Fund (WWTF) [LS20-065], the European Research Council Grant [866533-CORTIGRAD], the National Natural Science Foundation of China [Grant No. 81790652, No.81790650] and the NAM Advanced Biomedical Imaging Program [FY2016] between Nanyang Technological University, Singapore and Medical University of Vienna, Austria

Individuality manifests in the dynamic reconfiguration of large-scale brain networks during movie viewing

Individuality, the uniqueness that distinguishes one person from another, may manifest as diverse rearrangements of functional connectivity during heterogeneous cognitive demands; yet, the neurobiological substrates of individuality, reflected in inter-individual variations of large-scale functional connectivity, have not been fully evidenced. Accordingly, we explored inter-individual variations of functional connectivity dynamics, subnetwork patterns and modular architecture while subjects watched identical video clips designed to induce different arousal levels. How inter-individual variations are manifested in the functional brain networks was examined with respect to four contrasting divisions: edges within the anterior versus posterior part of the brain, edges with versus without corresponding anatomically-defined structural pathways, inter- versus intra-module connections, and rich club edge types. Inter-subject variation in dynamic functional connectivity occurred to a greater degree within edges localized to anterior rather than posterior brain regions, without adhering to structural connectivity, between modules as opposed to within modules, and in weak-tie local edges rather than strong-tie rich-club edges. Arousal level significantly modulates inter-subject variability in functional connectivity, edge patterns, and modularity, and particularly enhances the synchrony of rich-club edges. These results imply that individuality resides in the dynamic reconfiguration of large-scale brain networks in response to a stream of cognitive demands.ope