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Open research questions in Functional Brain Connectivity Studies

439 unresolved questions extracted from the limitations and future-work sections of 1,407 Functional Brain Connectivity Studies papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Evidence in older populations remains critically limited, - Findings from young adults cannot be directly generalized to older adults, - Age-related morphological, physiological, and connectivity changes affect the generalizability of the results

    Integrating computational modeling, neuroimaging, and neuromodulation to decompose perceptual decision-making in healthy aging: a review of methods, findings, and gaps · 2026 · DOI

  • Systematic investigation at the intersection of cognitive modeling and neuromodulation to selectively improve distinct components of perceptual decision-making in aging, - Bridging the gap between computational models, brain mechanisms, and causal interventions

    Integrating computational modeling, neuroimaging, and neuromodulation to decompose perceptual decision-making in healthy aging: a review of methods, findings, and gaps · 2026 · DOI

  • the sample is small, - the field is increasingly aware of the need for large samples to establish reliable brain-behavior relationships, - while we were able to leverage an additional datapoint two weeks before camp for half the sample thereby approximating a 'waitlist' control, given adolescent/family scheduling constraints the randomization was not fully implemented, which limits causal inference, - the study did not incorporate an active control condition

    Changes in resting-state functional connectivity between large-scale brain networks after an intensive arts intervention for adolescents with depression · 2026 · DOI

  • Functional mapping of large-scale brain networks within subcortical regions is hindered by methodological barriers. There is a need for novel analytic techniques to overcome prior methodological barriers in separating overlapping networks. The study aims to address this gap by employing a novel analytic technique called NASCAR.

    Functional fractionation of large-scale brain networks in the human subcortex · 2026 · DOI

  • Investigating the neural mechanisms underlying fear learning and anxiety disorders in larger and more diverse samples, - Examining the effects of novel treatment options, such as fMRI-guided neurofeedback or transcranial magnetic stimulation, on anxiety disorders, - Investigating the relationship between the default mode network and other brain networks in fear learning and anxiety disorders

    Intrinsic connectivity networks during fear and safety learning in youth · 2026 · DOI

  • The study aims to address the gap in understanding the changes in functional connectivity during fear learning in youth. The study investigates the differences in connectivity within and between the salience network, executive control network, and default mode network throughout fear learning. The study aims to identify potential neural targets for novel treatment options.

    Intrinsic connectivity networks during fear and safety learning in youth · 2026 · DOI

  • macroscopic behavior does not admit a closed-form solution outside of certain constraints, - some aspects of the QIF network are not captured by the mean-field, - limited to specific types of neural mass models

    Data-driven mean-field within whole-brain models · 2026 · DOI

  • exploring other types of neural mass models, - applying the method to different types of data, - investigating the use of other machine learning algorithms

    Data-driven mean-field within whole-brain models · 2026 · DOI

  • The need to better understand the underlying mechanisms driving AD onset and progression. The lack of a quantitative approach for studying complex biological dynamics across heterogeneous individuals. The need for personalized modeling of progressive biological processes.

    Data-driven modeling of spatiotemporal dynamics using multimodal imaging data · 2026 · DOI

  • Previous studies examined network controllability using white matter tractography, neglecting the contributions of gray matter. The neurobiological mechanisms by which network architectures shape dysfunctional dynamic transitions in MDD have not been extensively examined.

    Controllability of morphometric network colocalize with underlying neurobiology in major depression · 2026 · DOI

  • Treatment resistance and suboptimal outcomes in psychiatric disorders. The remaining obscurity of disease mechanisms. Head motion and other sources of variance can affect the functional connectivity measurement.

    Distinct and common subcortical functional connectivity revealed across three major psychiatric disorders · 2026 · DOI

  • The fine intra- and inter-subcortical patterns are less known. The disease mechanisms of schizophrenia, bipolar disorder, and major depressive disorder are not well understood.

    Distinct and common subcortical functional connectivity revealed across three major psychiatric disorders · 2026 · DOI

  • The paper identifies a gap in understanding how brain-behavior associations vary across different environmental contexts. Prior work has often operated under the assumption that neural networks linked to psychopathology function in the same way across different individuals. The study seeks to address this gap by examining differences in psychological symptoms and brain network functional connectivity across three clusters of youth.

    Childhood environment clusters reveal heterogeneous associations between large-scale brain networks and youth mental health symptoms · 2026 · DOI

  • Utilizing genome-wide information gleaned from GWASs and mathematical algorithms could shed promising light on the shared and unique genetic underpinning of two disorders, - Further research is needed to carve up the biological delineator for each disorder, - Investigating the genetic relationships between BD and SCZ and their relationships with brain network connectivity alterations

    Schizophrenia and bipolar disorder: a comparative analysis of genetic and brain network connectivity · 2026 · DOI

  • The inconsistent findings across prior studies due to methodological differences and small sample sizes. The complexity of analyzing and interpreting gene expression data in the context of brain function. The need to account for spatial autocorrelation and heterogeneity in the analysis of brain activity and gene expression.

    Intrinsic regional brain activity differences and its relationship with neurotransmitter and gene expression in postpartum depression: a voxel-based meta-analysis · 2026 · DOI

  • investigate the effects of insomnia treatment on brain network alterations, - examine the relationship between insomnia and cognitive decline in MDD, - explore the neural mechanisms underlying insomnia-related changes in DMN-medial VAN connectivity

    Insomnia severity impact dynamic connectivity and modulate connectivity-cognitive links in major depressive disorder · 2026 · DOI

  • The current study aims to address the gap in understanding the relationship between insomnia severity and dynamic functional connectivity in MDD. Prior studies have focused on static functional connectivity, and the current study explores dynamic functional connectivity. The study also aims to identify insomnia-related changes in brain network connectivity and their impact on cognitive functions, which is a gap in current research.

    Insomnia severity impact dynamic connectivity and modulate connectivity-cognitive links in major depressive disorder · 2026 · DOI

  • the number of non-adult studies is too small to conduct a subgroup analysis, - study heterogeneity was assessed using a whole-brain voxel-based jackknife sensitivity analysis, - the analysis was limited to studies comparing amygdala-based whole-brain resting-state functional connectivity in patients with anxiety disorders versus healthy controls

    Altered amygdala resting-state functional connectivity in anxiety disorders: a coordinate-based meta-analysis · 2026 · DOI

  • future studies could investigate the neural target for biomarker development and intervention strategies, - examining potential hemispheric differences in amygdala connectivity could be a direction for future research, - refining the neurofunctional connectivity model of anxiety disorders could be a future research direction

    Altered amygdala resting-state functional connectivity in anxiety disorders: a coordinate-based meta-analysis · 2026 · DOI

  • The relationship between GABA levels and functional connectivity in psychosis spectrum disorders is under-investigated. The mechanisms underlying altered neurometabolic activity and connectivity in psychosis spectrum disorders are not well understood.

    Network functional connectivity and anterior cingulate cortex gamma-aminobutyric acid in antipsychotic medication-naïve first-episode psychosis patients · 2026 · DOI

  • Investigating potential PTSD biomarkers from a new perspective by combining structural and functional images. Linking changes in SFC to the underlying molecular architecture. Exploring the pathogenesis and molecular mechanisms of PTSD further.

    Variations of structural–functional coupling in post-traumatic stress disorder are associated with underlying molecular and transcriptional features · 2026 · DOI

  • The current understanding of PTSD neurobiology is incomplete. Prior studies have been limited by their single-modal experimental design.

    Variations of structural–functional coupling in post-traumatic stress disorder are associated with underlying molecular and transcriptional features · 2026 · DOI

  • further research is needed to understand the underlying mechanisms of brain aging in depression, - investigation of the effects of treatment on brain-PAD is required

    Depression and aging: insights from brain age prediction models · 2026 · DOI

  • Understanding the neural basis of attentional deficits could guide the development of augmentation approaches to better target cognitive difficulties in MDD, - Noninvasive brain stimulation (neuromodulation) techniques that modify brain networks could play an important role, - Further research is needed to examine the relationship between IIV and brain network connectivity in MDD

    Functional connectivity correlates of reaction time variability in treatment-resistant major depression · 2026 · DOI

  • The study did not explore the transregional connectivity differences among MDD subtypes and healthy controls in previous works, - The analysis was restricted to the left hemisphere data due to limited bilateral sampling in AHBA donors

    Heterogeneity of brain functional connectivity, transcriptome, and neurotransmitter profiles in major depressive disorder · 2025 · DOI

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439 open questions have been extracted from the limitations and future-work passages of 1,407 Functional Brain Connectivity Studies papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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