Biology subjects

Hallquist, M. N.

Publications and source records attributed to Hallquist, M. N..

9 recordsLinked to original sources

bioRxiv2025

Prefrontal and Subcortical Value Representation during Explore-Exploit Decision-Making and Suicide Attempts

BackgroundThis study aims to understand learning and decision-making in suicidal behavior by investigating temporal dynamics of reward value encoding in individuals with late-life depression and a history of suicide attempts. MethodsIn a retrospective case-control study, 134 older adults (33 with depression and history of suicide attempts, 29 with depression and suicidal ideation but no past attempts, 32 with depression and no suicidal ideation/past attempts, and 40 psychiatrically healthy controls) completed an explore-exploit decision-making task during functional MRI (fMRI). Multilevel models of deconvolved fMRI time series, time-locked to trial events, interrogated whether temporal patterns of reward value encoding was associated with suicidal behavior. ResultsSuicidal behavior in general was associated with blunted ventral PFC (vPFC) value signals, but profiles varied as a function of attempt lethality. Specifically, low-lethality suicide attempts and excessive behavioral shifts were associated with abolished phasic responses to value updates in the default network vPFC and its connected regions, including the striatum, amygdala, and hippocampus. Additionally, an unexpected pattern of sustained negative value responses was observed in vPFC and striatal control subregions, and hippocampus of high-lethality suicide attempters. ConclusionsDiverging patterns of decision-related responses may reflect different paths toward suicidal behavior. Impaired value updating in individuals with low-lethality suicide attempts suggests a failure to integrate recent outcomes alongside prior experience, potentially relating to over-reactivity to stressors and a lower threshold for suicide attempts. In contrast, increased control network responses to difficult choices in high-lethality attempters may underlie cognitive constriction and consideration of a narrow set of potential solutions.

neuroscience↗

bioRxiv2025

Prefrontal default-mode network interactions with posterior hippocampus during exploration

Hippocampal maps and ventral prefrontal cortex (vPFC) value and goal representations support foraging in continuous spaces. How might hippocampal-vPFC interactions control the balance between behavioral exploration and exploitation? Using fMRI and reinforcement learning modeling, we investigated vPFC and hippocampal responses as humans explored and exploited a continuous one-dimensional space, with out-of-session and out-of-sample replication. The spatial distribution of rewards, or value landscape, modulated activity in the hippocampus and default network vPFC subregions, but not in ventrolateral prefrontal control subregions or medial orbitofrontal limbic subregions. While prefrontal default network and hippocampus displayed higher activity in less complex, easy-to-exploit value landscapes, vPFC-hippocampal connectivity increased in uncertain landscapes requiring exploration. Further, synchronization between prefrontal default network and posterior hippocampus scaled with behavioral exploration. Considered alongside electrophysiological studies, our findings suggest that locations to be explored are identified through coordinated activity binding prefrontal default network value representations to posterior hippocampal maps. Significance StatementThe ventral prefrontal cortex represents goals and values, while the hippocampus contains maps of physical and abstract spaces. In recent years, neuroscientists have sought to understand how hippocampal-prefrontal interactions help us to solve complex problems such as deciding whether to exploit known rewards or explore in search of better alternatives. Using functional magnetic resonance imaging and reinforcement learning modeling, we examine these interactions as humans explore and exploit an environment with a complex distribution of rewards or value landscape. We describe how this value landscape modulates activity and connectivity between prefrontal cortex and hippocampus, controlling the balance between exploration and exploitation.

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bioRxiv2024

Impulsive adolescents exhibit inefficient processing and a low decision threshold when decoding facial expressions of emotions

BackgroundBorderline personality disorder (BPD) is a debilitating psychiatric illness whose symptoms frequently emerge during adolescence. Initial studies in adults suggest that the interpersonal difficulties common in BPD may emerge from disrupted processing of social and emotional stimuli. Less is known about these processes in adolescents with BPD symptoms, despite substantial changes in socioemotional processing during this developmental period. Methods86 adolescents and young adults with and without BPD symptoms completed an emotional interference task involving the identification of a facial emotion expression in the presence of a conflicting or congruent emotion word. We used hierarchical drift diffusion modeling to index speed of processing and decision boundary. Using Bayesian multilevel regression, we characterized age-related differences in facial emotion processing. We then examined whether BPD symptom dimensions were associated with facial emotion processing on this task. To determine the specificity of our effects, we analyzed behavioral data from a corresponding nonemotional interference task. ResultsImpulsivity, but not negative affectivity or interpersonal dysfunction, predicted inefficient processing when presented with conflicting negative emotional stimuli. Across both tasks, impulsivity in adolescents was further associated with a lower decision boundary. Impulsive adolescents were especially likely to make fast, but inaccurate decisions about another persons emotional state. ConclusionImpulsive adolescents with BPD symptoms are prone to making errors when appraising facial expressions of emotions, which may potentiate or worsen interpersonal conflicts. Our findings highlight the role of lower-level social cognitive processes in interpersonal difficulties among vulnerable youth during a sensitive developmental window.

neuroscience↗

bioRxiv2023

Generalizable links between symptoms of borderline personality disorder and functional connectivity

BackgroundSymptoms of borderline personality disorder (BPD) often manifest in adolescence, yet the underlying relationship between these debilitating symptoms and the development of functional brain networks is not well understood. Here we aimed to investigate how multivariate patterns of functional connectivity are associated with symptoms of BPD in a large sample of young adults and adolescents. MethodsWe used high-quality functional Magnetic Resonance Imaging (fMRI) data from young adults from the Human Connectome Project: Young Adults (HCP-YA; N = 870, ages 22-37 years, 457 female) and youth from the Human Connectome Project: Development (HCP-D; N = 223, age range 16-21 years, 121 female). A previously validated BPD proxy score was derived from the NEO Five Factor Inventory (NEO-FFI). A ridge regression model with 10-fold cross-validation and nested hyperparameter tuning was trained and tested in HCP-YA to predict BPD scores in unseen data from regional functional connectivity, while controlling for in-scanner motion, age, and sex. The trained model was further tested on data from HCP-D without further tuning. Finally, we tested how the connectivity patterns associated with BPD aligned with agerelated changes in connectivity. ResultsMultivariate functional connectivity patterns significantly predicted out-of-sample BPD proxy scores in unseen data in both young adults (HCP-YA; pperm = 0.001) and older adolescents (HCP-D; pperm = 0.001). Predictive capacity of regions was heterogeneous; the most predictive regions were found in functional systems relevant for emotion regulation and executive function, including the ventral attention network. Finally, regional functional connectivity patterns that predicted BPD proxy scores aligned with those associated with development in youth. ConclusionIndividual differences in functional connectivity in developmentally-sensitive regions are associated with the symptoms of BPD.

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bioRxiv2023

The Dark Side of Mentalizing: Learning Signals in the Default Network During Social Exchanges Support Cooperation and Exploitation

The evolution of human social cognitive capacities such as mentalizing was associated with the expansion of frontoparietal cortical networks, particularly the default network. Mentalizing supports prosocial behaviors, but recent evidence indicates it may also serve a darker side of human social behavior. Using a computational reinforcement learning model of decision-making on a social exchange task, we examined how individuals optimized their approach to social interactions based on a counterparts behavior and prior reputation. We found that learning signals encoded in the default network scaled with reciprocal cooperation and were stronger in individuals who were more exploitative and manipulative, but weaker in those who were more callous and less empathic. These learning signals, which help to update predictions about others behavior, accounted for associations between exploitativeness, callousness, and social reciprocity. Separately, we found that callousness, but not exploitativeness, was associated with a behavioral insensitivity to prior reputation effects. While the entire default network was involved in reciprocal cooperation, sensitivity to reputation was selectively related to the activity of the medial temporal subsystem. Overall, our findings suggest that the emergence of social cognitive capacities associated with the expansion of the default network likely enabled humans to not only cooperate effectively with others, but to exploit and manipulate others as well. SignificanceTo navigate complex social lives, humans must learn from their interactions with others and adjust their own behavior accordingly. Here, we show that humans learn to predict the behavior of social counterparts by integrating reputational information with both observed and counterfactual feedback acquired during social experience. We find that superior learning during social interactions is related to empathy and compassion and associated with activity of the brains default network. Paradoxically however, learning signals in the default network are also associated with manipulativeness and exploitativeness, suggesting that the ability to anticipate others behavior can serve both the light and dark sides of human social behavior.

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bioRxiv2022

Right anterior insula effective connectivity impairs intrinsic BOLD fluctuations in dorsal attention network in adolescents and young adults with borderline personality symptoms

BackgroundBorderline Personality Disorder (BPD) symptoms often emerge in adolescence. However, little is known about the functional organization of intrinsic brain networks in young people with BPD symptoms. MethodsIn this study we collected resting-state fMRI data in a sample of adolescents and young adults with (nBPD = 40) and without BPD (nHC= 42) symptoms. Using a detailed cortico-limbic parcellation coupled with graph theoretical analyses, we tested for group and age-related differences in regional functional and effective connectivity (FC, EC) and amplitude of low frequency fluctuations (ALFF). We conducted a series of analyses that progressed from global network properties to focal tests of EC amongst nodes in Salience (SN) and Dorsal Attention Networks (DAN). ResultsAt the regional level, regularized regression analyses revealed a broad pattern of hyper-connectivity and heightened ALFF in R dorsal anterior insula (daIns), in addition to hypoconnectivity in R temporal-parietal junction (TPJ) and decreased ALFF in multiple DAN regions. Furthermore, analyses of EC amongst daIns, TPJ, and DAN revealed that in BPD participants daIns exerts a heightened influence on TPJ and DAN regions. Finally, multivariate mediation models indicated that lower DANALFF was differentially predicted by EC from TPJ and daIns. ConclusionsOur findings provide converging evidence that heightened EC from daIns impairs network-wide ALFF in DAN both directly and indirectly via impaired TPJ functioning. We interpret this pattern of findings in line with an "attentional hijacking" account of borderline personality.

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bioRxiv2021

Dissociation in basolateral and central amygdala effective connectivity predicts the stability of emotion-related impulsivity in adolescents with borderline personality symptoms: a resting-state fMRI study

BackgroundBorderline personality disorder (BPD) is associated with altered activity in the prefrontal cortex (PFC) and amygdala, yet no studies have examined fronto-limbic circuitry in borderline adolescents. Here, we examined the contribution of fronto-limbic connectivity to the longitudinal stability of emotion-related impulsivity (ERI), a key feature of BPD, in symptomatic adolescents and young adults. MethodsWe compared resting-state effective connectivity (EC) in 82 adolescents and emerging adults with and without clinically significant borderline symptoms (n BPD = 40, ages 13-30). Group-specific directed networks were estimated amongst fronto-limbic nodes including PFC, ventral striatum (VS), central amygdala (CeN), and basolateral amygdala (BLA). We calculated directed centrality metrics and examined if these values were associated with initial levels and rates of change in ERI symptoms over a one-year follow-up using latent growth curve models (LGCMs). ResultsIn the healthy group, ventromedial prefrontal cortex (vmPFC) and dorsal ACC had a directed influence on CeN and VS respectively. In the borderline group bilateral BLA had a directed influence on CeN, whereas in the healthy group CeN influenced BLA. LGCMs revealed that in borderline adolescents, ERI remained stable across follow-ups. Further, higher output of R CeN in controls was associated with stronger within-person decreases in ERI. ConclusionsFunctional inputs from BLA and vmPFC appear to play competing roles in influencing CeN activity. In borderline adolescents BLA may predominate over CeN activity, while in controls the ability of CeN to conversely influence BLA activity is associated with more rapid reductions in ERI.

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bioRxiv2020

Encoding of reinforcement along the hippocampal long axis and the transition from exploration to exploitation

When making decisions, should one exploit known good options or explore potentially better alternatives? Exploration of spatially unstructured options depends on the neocortex, striatum, and amygdala. In natural environments, however, better options often cluster together, forming structured value distributions. The hippocampus binds reward information into allocentric cognitive maps to support navigation and foraging in such spaces. Using a reinforcement learning task with a spatially structured reward function, we show that human posterior hippocampus (PH) invigorates exploration while anterior hippocampus (AH) supports the transition to exploitation. These dynamics depend on differential reinforcement representations in the PH and AH. Whereas local reward prediction error signals are early and phasic in the PH tail, global value maximum signals are delayed and sustained in the AH body. AH compresses reinforcement information across episodes, updating the location and prominence of the value maximum and displaying goal cell-like ramping activity when navigating toward it.

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bioRxiv2018

Graph theory approaches to functional network organization in brain disorders: A critique for a brave new small-world

Over the past two decades, resting-state functional connectivity (RSFC) methods have provided new insights into the network organization of the human brain. Studies of brain disorders such as Alzheimers disease or depression have adapted tools from graph theory to characterize differences between healthy and patient populations. Here, we conducted a review of clinical network neuroscience, summarizing methodological details from 106 RSFC studies. Although this approach is prevalent and promising, our review identified four challenges. First, the composition of networks varied remarkably in terms of region parcellation and edge definition, which are fundamental to graph analyses. Second, many studies equated the number of connections across graphs, but this is conceptually problematic in clinical populations and may induce spurious group differences. Third, few graph metrics were reported in common, precluding meta-analyses. Fourth, some studies tested hypotheses at one level of the graph without a clear neurobiological rationale or considering how findings at one level (e.g., global topology) are contextualized by another (e.g., modular structure). Based on these themes, we conducted network simulations to demonstrate the impact of specific methodological decisions on case-control comparisons. Finally, we offer suggestions for promoting convergence across clinical studies in order to facilitate progress in this important field.

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