Biology subjects

Ziaei, M.

Publications and source records attributed to Ziaei, M..

13 recordsLinked to original sources

bioRxiv2026

Organization of functional brain networks architecture during negative movie watching in late adulthood

Most evidence on age-related network topology derives from resting-state paradigms, leaving unclear how aging alters brain organization during naturalistic processing and whether graph-theoretical metrics relate to emotional and cognitive functioning in ecologically valid contexts. We analyzed movie-fMRI and behavioral data from 72 younger and 68 older adults, examining global (small-worldness, clustering coefficient, characteristic path length), network (participation coefficient), and nodal (degree centrality, betweenness centrality, nodal efficiency) properties. Regression models were used to test associations between nodal measures and both the Emotional Resilience Index (ERI) and the Cognitive Function Index (CFI), while mediation analyses were conducted to test whether nodal measures mediate the relationship between age and ERI. Older adults exhibited increased characteristic path length and clustering coefficient, indicating reduced global integration and greater local segregation. Although small-world organization was preserved in two groups, there was less pronounced small-world architecture in older adults compared to younger adults, suggesting a shift toward more regularized, locally clustered networks and reduced long-range connections during dynamic stimuli. Participation coefficient values were higher in the somatomotor, frontoparietal, and default mode networks, and lower in the subcortical network, among older adults reflecting greater between-network integration in cortical networks but diminished subcortical coordination in aging. Five key nodes, two thalamic regions, hippocampus, and two insular regions, showed reduced centrality and efficiency in older adults during the negative movie, indicating weakened dominance of subcortical hubs under emotional salience condition. Right thalamic nodal properties were negatively associated with ERI and CFI and served as mediators in the relationship between age and emotional resilience. These findings suggest that reduced thalamic hub centrality may reflect adaptive recalibration of salience emotional processing, linking network reorganization to improved emotional resilience in aging. Key pointsO_LIOlder adults showed higher path length and clustering, suggesting reduced integration. C_LIO_LIReduced small-worldness reflects weaker balance of segregation and integration with age. C_LIO_LIOlder adults showed higher cortical but lower subcortical participation coefficients. C_LIO_LIKey nodes showed reduced centrality during negative stimuli, indicating weaker hubs. C_LIO_LIRight thalamus changes linked to resilience, mediating age-emotion relationships. C_LI

neuroscience↗

bioRxiv2026

Age-related reconfiguration of locus coeruleus-cortical functional organization

The locus coeruleus (LC) regulates attention, arousal, and adaptive behavior via widespread noradrenergic projections to cortex, yet its large-scale cortical organization and age-related vulnerability remain poorly understood. Using 7T MRI during naturalistic movie-viewing with neutral and negative emotional valence, study-specific LC delineation, and PET-derived receptor-transporter maps, we characterized LC-linked cortical organization in younger and older adults. Functional gradient analysis revealed two dominant axes: a stable primary gradient anchored by catecholaminergic receptor-transporter distributions, and a context-sensitive secondary gradient aligning with the visual-somatomotor (V-S) axis in neutral movie-viewing and the sensorimotor-association (S-A) axis in negative movie-viewing. During negative movie-viewing, older adults exhibited higher global and within-frontoparietal control network dispersion, indicating reduced functional differentiation, a pattern further associated with poorer emotional wellbeing. By revealing chemoarchitectural and context-sensitive LC-linked cortical organization, current work identifies mechanisms underlying age-related LC-linked cortical reorganization with consequences for mental health.

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bioRxiv2026

Functional connectivity profile of the amygdala subfields associates with emotional well-being in aging

Amygdala-related functional connectivity plays a crucial role in human emotion, cognition, and mental well-being. The amygdala is a highly heterogeneous structure, with subregions that have both distinct and overlapping functions. However, the connectivity patterns of different amygdala subregions--and how these associations vary with age--remain poorly understood. Functional MRI data were analyzed from 68 younger adults and 66 older adults during movie watching in a 7T MRI scanner. Partial least squares (PLS) analysis was used to identify latent variables capturing variance associated with age-related differences in the functional connectivity patterns of three amygdala subregions: the basolateral (BLA), centromedial (CMA), and superficial (SFA) nuclei. In addition, covariance between behavioral measures, such as emotional resilience and cognitive function, and functional connectivity of these subregions was examined. We further explored the associated cognitive processes, correspondence with large-scale brain networks, and the underlying chemoarchitecture of the identified connectivity patterns of the BLA, CMA, and SFA. Multivariate analyses revealed age-related and subregion-specific functional connectivity patterns. Functional connectivity patterns of amygdala subregions were further associated with emotional resilience, which largely overlapped across widespread brain regions; however, their associations differed by age. Stronger coupling of amygdala subregions predicted higher resilience in older adults but lower resilience in younger adults. The identified connectivity patterns were linked to the salience, control, and default mode networks and showed spatial correspondence with mGluR5 and 5-HT6 receptor distributions. These findings highlight age-dependent reorganization of amygdala-related networks that support emotional resilience and provide novel insights into how functional and neurochemical changes of the amygdala subregions contribute to adaptive emotional and cognitive functions in aging.

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bioRxiv2025

Frontoparietal functional dedifferentiation during naturalistic movie watching among older adults at risk of emotional vulnerability

Functional dedifferentiation, a hallmark of brain aging particularly evident within the frontoparietal network (FPN), has been extensively investigated in the context of cognitive decline, yet its implications for late-life mental health remain poorly understood. Leveraging naturalistic fMRI combined with gradient mapping techniques, the present study investigated FPN functional dedifferentiation--quantified by functional dispersion of FPN in the multidimension gradient manifold--during real-life emotional experiences and its link to affective outcomes. Here, we estimated functional dispersion during naturalistic movie watching in both younger (N=72, 34 female, 19-36 yrs) and older (N=68, 36 female, 65-82 yrs) adult groups with 7T MRI scanner and assessed their emotion regulation difficulties, anxiety, and depression symptoms as indicators of mental health status. The results demonstrated that greater FPN dispersion (i.e., more dissimilar connectivity) was linked to increased depressive symptoms in older adults and highlighted emotion regulation difficulties as a full mediator of this relationship. Moreover, FPN dispersion could distinguish emotionally resilient from vulnerable older individuals. These findings suggest that functional dedifferentiation of the FPN during ecologically valid emotional context constitutes a promising neural signature of affective vulnerability in older adults. By bridging age-related functional dedifferentiation to real-world emotional scenario, this work underscores the translational value of naturalistic paradigms in geriatric psychiatry and identifies potential intervention targets aimed at enhancing FPN specificity to promote mental health in aging population.

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bioRxiv2025

Compression of functional gradients from rest to naturalistic processing: Moderation effect of age

The functional cortical hierarchy of the human brain, a fundamental principle of brain organization, has been extensively characterized during resting state for healthy younger adults. However, functional re-organization during naturalistic settings, such as movie-watching, and its alterations across the adult lifespan remains poorly understood. Using resting-state and movie fMRI data from two large datasets, Cam-CAN (N=416) and DyNAMiC (N=156), this study conducted a comprehensive comparison of brain organization across two states. We identified a robust reorganization with compression of functional gradients from rest to movie-watching states, which is mediated by changes in functional integration and segregation of brain networks. The extent of compression from rest to movie was significantly greater in older adults and predicted worse cognitive performance among the elderly population. Our findings provide novel insights into how macroscale brain hierarchy is reorganized during naturalistic processing, and how this reorganization during aging impacts cognitive processes, offering a deeper understanding of the neural basis of aging and cognition.

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bioRxiv2024

Age-related Increase in Locus Coeruleus Activity and Connectivity with Prefrontal Cortex during Ambiguity Processing

Interpreting ambiguous environmental cues, like facial expressions, becomes increasingly challenging with age, especially as cognitive resources decline. Managing these challenges requires adaptive neural mechanisms that are essential for maintaining mental well-being. The locus coeruleus (LC), the brains main norepinephrine source, regulates attention, arousal, and stress response. With extensive cortical connections, the LC supports adapting to cognitive demands and resolving conflicting cues from environment, particularly in later life. Previous research suggests that LC interacts with the prefrontal cortex (PFC) during high-conflict tasks. However, whether LC activity and its connectivity with the PFC support emotional ambiguity processing and contributes to emotional well-being in healthy aging remains unclear. To address this gap, we used 7T-MRI to examine LC function in 75 younger (25.8 {+/-} 4.02years, 35females) and 69 older adults (71.3 {+/-} 4.1 years, 35females) during facial-emotion-recognition task morphed with varying ambiguity: anchor (unambiguous happy or fearful), intermediate-ambiguity (30%happy-70%fearful and 40%happy-60%fearful expressions), and absolute-ambiguity (50%happy-fearful). Behaviorally, participants had longer response times and lower confidence during the absolute-ambiguity condition, while older adults perceived ambiguous faces as happy more frequently than younger adults. Neuroimaging results revealed older adults exhibited greater LC activity and enhanced connectivity with dorsolateral PFC (dlPFC) during absolute-ambiguity compared to younger adults. This heightened connectivity in older adults was linked to better task-independent self-reported mental well-being questionnaires and greater emotional resilience scores derived from principal component analysis. Overall, these findings suggest that greater LC activity supports managing cognitively demanding tasks, while enhanced LC-dlPFC connectivity promotes emotional well-being, highlighting this neural pathways role in healthy aging. Significance StatementUnderstanding how the brain adapts to cognitive and emotional demands with age is key to promoting healthy aging. This study examined whether the locus coeruleus (LC), a brain region critical for regulating attention and arousal, undergoes adaptive changes with age, especially during emotional ambiguity task. Using ultra-high-field imaging, we explored younger and older adults recognize facial expressions with varying ambiguity levels. Our findings indicated that compared to young, older adults showed heightened LC activity and LC-dorsolateral prefrontal cortex (dlPFC) connectivity when processing absolute-ambiguous facial expressions, with enhanced connectivity linked to improved mental well-being. These results suggest higher LC activity supports cognitive demands of ambiguity processing with LC-dlPFC connectivity promoting emotional well-being and resilience, offering insights into mechanisms underlying healthy aging.

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bioRxiv2024

Increased functional integration of emotional control network in late adulthood

Emotional wellbeing has often been shown to improve across the adult lifespan. The corresponding effects, however, in the emotion regulation brain networks remain underexplored. By utilizing large-scale datasets such as the Human Connectome Project (HCP-Aging, N=621, 349 females) and Cambridge Centre for Ageing and Neuroscience (Cam-CAN, N=333, 155 females), we were able to investigate how emotion regulation networks functional topography differs across the entire adult lifespan. Based on previous meta-analytic work that identified four large-scale functional brain networks involved in emotion generation and regulation, we investigated the association between the integration of these emotion regulation networks and measures of mental wellbeing with age in the HCP-Aging dataset. We found an increased functional integration of the emotional control network among older adults, which was replicated using the Cam-CAN dataset. Further we found that the interoceptive network, which is mediating emotion generative and regulative processes and carries our introspective and reflective functions, is less integrated in higher age. Our study highlights the importance of identifying topological changes in the functional emotion network architecture across the lifespan, as it allows for a better understanding of functional brain network changes that accompany emotional aging. HighlightsO_LIWe aimed to identify age-related differences in the functional integration of large-scale emotion regulation brain networks across the adult lifespan, and its implications for well-being. C_LIO_LIFrontal emotion control network showed increased while interoception network showed decreased functional integration with higher age in the HCP-Aging dataset. C_LIO_LIIncreased integration of emotion control network was replicated and validated in the Cam-CAN dataset. C_LI

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bioRxiv2023

Resilience-driven neural synchrony during naturalistic movie watching: an ultra-high field fMRI study

Psychological resilience protects individuals against the negative consequences of exposure to adversity. Despite increasing attention given to resilience for its role in maintaining mental health, a clear conceptualization of resilience remains elusive, and the intricacies of its neural correlates are poorly understood. Here, we recorded brain activity in healthy young adults using a 7T MRI scanner while they naturally watched movies. Stronger and more extensive resilience-driven neural synchrony, as estimated by inter-subject correlation, was observed in a wider set of brain regions in response to the negative movie compared to the neutral movie. Moreover, we found that high-resilience individuals had similar neural activities to their peers, while low-resilience individuals showed more variable neural activities. Intolerance of uncertainty (IU), a personality trait that shapes biased perception and cognition, damped the resilience-driven brain synchrony in regions related to attention, indicating IU may compromise resilience by affecting attentional functions. We propose that similarity of neural responses among resilient individuals highlights adaptive emotional processing. Conversely, the variability in neural responses indicates vulnerability to adverse psychological outcomes. These insights shed light on the mechanisms of resilience, highlighting that it operates as a system encompassing multiple neuropsychological processes crucial for adapting to external stimuli.

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bioRxiv2020

Assumptions belief load impacts brain networks underlying logical reasoning

Prior knowledge and beliefs influence our reasoning in daily life and may lead us to draw unwarranted conclusions with undesirable consequences. The underlying neural correlates of the interaction between belief and logic, prior to making logical decisions, are largely unknown. In this study, we aimed to identify brain regions important in distinguishing belief load of assumptions in logical decision making. Thirty-one healthy volunteers (18-29 years old) participated in an fMRI study and were asked to respond to a series of syllogistic arguments in which assumptions were either congruent (believable) or incongruent (unbelievable) with common knowledge. An interpretable machine learning algorithm, an L1 regularized Support Vector Machine, was used to explain the discriminatory pattern of conditions given the brain activation patterns. Behavioral results confirmed that believable premises were incorrectly endorsed more than unbelievable ones. Imaging results revealed that several connectivity patterns anchored around the insula, amygdala, and IFG were important in distinguishing believable from unbelievable assumptions at different time points preceding logical decisions. Our convergent behavioral and imaging results underscore the importance of the belief loads of our assumptions for a logically sound decision. Our results provide new insights into neural and potential cognitive mechanisms underlying the interaction between belief and logic systems, with important practical implications for social, complex decisions. HighlightsO_LIBelief load of premises impact logical decisions C_LIO_LIRegional importance in distinguishing belief load changes in different TRs C_LIO_LIBelief load of assumptions elicits emotional and salience responses C_LIO_LIRegional connectivity changes as the reasoning process evolves at different TRs C_LIO_LIInsula, caudate, amygdala, and IFG were among highly connected hubs during the task C_LI SignificanceIt has been experimentally shown that decision-makers often ignore given assumptions in favor of their own beliefs, potentially leading them towards a subjective rather than a logical decision. Consider "Carbon emission tax" given the assumption of "global warming". If a decision-maker does not believe in "global warming", the final decision on "Carbon emission tax" is not driven by factual premises but by the personal belief of the decision-maker. Understanding neural mechanisms underlying the interaction between the decision-makers beliefs and factual premises sheds light on factors driving belief bias and potential interventions to circumvent it. The main contribution of this study is to investigate neural mechanisms in a logical reasoning task in which the belief load of the assumptions was manipulated.

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bioRxiv2020

Brain networks involved in empathy for positive and negative emotions in younger and older adults

Empathy, among other social-cognitive processes, changes across adulthood. More specifically, cognitive components of empathy (understanding anothers perspective) appear to decline with age, while findings for affective empathy (sharing anothers emotional state) are rather mixed. Structural and functional correlates underlying cognitive and affective empathy in aging and the extent to which valence affects empathic response in brain and behavior are not well understood yet. To fill these research gaps, younger and older adults completed a modified version of the Multifaceted Empathy Test, which measures both cognitive and affective empathy as well as empathic responding to both positive and negative stimuli (i.e., positive vs. negative empathy). Adopting a multimodal imaging approach and applying multivariate analysis, the study found that for cognitive empathy to negative emotions, regions of the salience network including the anterior insula and anterior cingulate were more involved in older than younger adults. For affective empathy to positive emotions, in contrast, younger and older adults recruited a similar brain network including main nodes of the default mode network. Additionally, increased structural integrity (fractional anisotropy values) of the posterior, but not the anterior, cingulum bundle was related to activation of default mode regions during affective empathy for positive emotions in both age groups. These findings provide novel insights into the functional networks subserving cognitive and affective empathy in younger and older adults and highlight the importance of considering valence in empathic response in aging research. Further this study, for the first time, underscores the role of the posterior cingulum bundle in higher-order social-cognitive processes such as empathy, specifically for positive emotions, in aging.

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bioRxiv2019

A new role of hippocampus during logical reasoning and belief bias in aging

Reasoning requires initial encoding of the semantic association between premises or assumptions, retrieval of these semantic associations from memory, and recombination of information to draw a logical conclusion. Currently-held beliefs can interfere with the content of the assumptions if not congruent and inhibited. This study aimed to investigate the role of the hippocampus and hippocampal networks during logical reasoning tasks in which the congruence between currently-held beliefs and assumptions varies. Participants of younger and older age completed a series of syllogistic reasoning tasks in which two premises and one conclusion were presented and they were required to decide if the conclusion logically followed the premises. The belief load of premises was manipulated to be either congruent or incongruent with currently-held beliefs. Our whole-brain results showed that older adults recruited the hippocampus during the premise integration stage more than their younger counterparts. Functional connectivity using a hippocampal seed revealed that older, but not younger, adults recruited a hippocampal network that included anterior cingulate and inferior frontal regions when premises were believable. Importantly, this network contributed to better performance in believable inferences, only in older adults group. Further analyses suggested that, in older adults group, the integrity of the left cingulum bundle was associated with the higher correct rejection of believable premises more than unbelievable ones. Using multimodal imaging, this study highlights the importance of the hippocampus during premise integration and supports the compensatory role of the hippocampal network during a logical reasoning task among older adults.

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bioRxiv2019

Age-related differences in structural and functional prefrontal networks during a logical reasoning task

In logical reasoning, difficulties in inhibition of currently-held beliefs may lead to unwarranted conclusions, known as belief bias. Aging is associated with difficulties in inhibitory control, which may lead to deficits in inhibition of currently-held beliefs. No study to date, however, has investigated the underlying neural substrates of age-related differences in logical reasoning and the impact of belief load. The aim of the present study was to delineate age differences in brain activity during a syllogistic logical reasoning task while the believability load of logical inferences was manipulated. Twenty-nine, healthy, younger and thirty, healthy, older adults (males and females) completed a functional magnetic resonance imaging experiment in which they were asked to determine the logical validity of conclusions. Unlike younger adults, older adults engaged a large-scale network including anterior cingulate cortex (ACC) and inferior frontal gyrus (IFG) during conclusion stage. Our functional connectivity results suggest that while older adults engaged the ACC network to overcome their intuitive responses for believable inferences, the IFG network contributed to higher control over responses during both believable and unbelievable conditions. Our functional results were further supported by structure-function-behavior analyses indicating the importance of cingulum bundle and uncinate fasciculus integrity in rejection of believable statements. These novel findings lend evidence for age-related differences in belief bias, with potentially important implications for decision making where currently-held beliefs and given assumptions are in conflict.

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bioRxiv2019

Longitudinal Automatic Segmentation of Hippocampal Subfields (LASHiS) using Multi-Contrast MRI

The volumetric and morphometric examination of hippocampus formation subfields in a longitudinal manner using in vivo MRI could lead to more sensitive biomarkers for neuropsychiatric disorders and diseases including Alzheimers disease, as the anatomical subregions are functionally specialised. Longitudinal processing allows for increased sensitivity due to reduced confounds of inter-subject variability and higher effect-sensitivity than cross-sectional designs. We examined the performance of a new longitudinal pipeline (Longitudinal Automatic Segmentation of Hippocampus Subfields [LASHiS]) against three freely available, published approaches. LASHiS automatically segments hippocampus formation subfields by propagating labels from cross-sectionally labelled time point scans using joint-label fusion to a non-linearly realigned single subject template, where image segmentation occurs free of bias to any individual time point. Our pipeline measures tissue characteristics available in in vivo high-resolution MRI scans, at both clinical (3 Tesla) and ultra-high field strength (7 Tesla) and differs from previous longitudinal segmentation pipelines in that it leverages multi-contrast information in the segmentation process. LASHiS produces robust and reliable automatic multi-contrast segmentations of hippocampus formation subfields, as measured by higher volume similarity coefficients and Dice coefficients for test-retest reliability and robust longitudinal Bayesian Linear Mixed Effects results at 7 T, while showing sound results at 3 T. All code for this project including the automatic pipeline is available at https://github.com/CAIsr/LASHiS

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