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Open research questions in Functional Brain Connectivity Studies

1,332 gap statements mined from Functional Brain Connectivity Studies papers in our 7.9M-paper local library, which holds 5,620 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • There is a lack of understanding of the association between obesity and premature pubarche and their effects on brain functional connectivity. Prior studies have not examined the effects of obesity on brain functional connectivity in girls with premature pubarche. Longitudinal studies are needed to determine the developmental significance of the findings.

    Obesity-Associated Differences in Brain Functional Connectivity in Girls with Premature Pubarche: A Preliminary Study · 2026 · DOI

  • Lack of objective neuroimaging biomarkers for identifying neurobiological subtypes. Need for a data-driven approach to parse the biological mechanisms underlying clinical heterogeneity.

    Edge-centric brain connectomes reveal two molecularly distinct neurobiological subtypes of adolescent major depressive disorder · 2026 · DOI

  • The neurofunctional effects of transient variations in 5-HT signaling have been highly inconsistent. There is a need to understand how individual variations in 5-HT-regulating genetic polymorphisms interact with acute tryptophan depletion to shape brain connectivity and architecture.

    State and trait serotonin variations interact to shape the intrinsic connectivity and gradient architecture of the brain – a combined TPH2 genetics and tryptophan depletion study in men · 2026 · DOI

  • Non-motor communication impairments remain under-explored, especially outside English-speaking cohorts. The neural underpinnings of linguistic deficits in patients with Lewy body diseases are not well understood. There is a need to investigate language network disruption in patients with Lewy body diseases using fMRI and graph theory analysis.

    Language network disruption in patients with Lewy body diseases · 2026 · DOI

  • Current network analyses are often constrained by fixed thresholding strategies and single-level observations. There is a need to move beyond traditional single-feature connectivity analyses to characterize high-dimensional spatiotemporal network dynamics.

    Multiscale EEG network alterations in adolescents with depressive symptoms: static–dynamic connectivity, topological features, and exploratory scalp-level network hubs · 2026 · DOI

  • The lack of understanding of neural mechanisms underlying adolescent MDD, particularly in terms of local BOLD-signal synchrony.

    Aberrant Regional Homogeneity in First-Episode, Drug-Naïve Adolescents with Major Depressive Disorder · 2026 · DOI

  • Future studies that incorporate actual physiological data across age groups would provide critical validation of the simulated results and enhance the relevance of our findings to functional outcomes. Expand the sample size of the youngest group. Including tissue conductivity as a variable may benefit from a more comprehensive understanding of age-related changes in cortical electric fields.

    Amplitude of Intracranial Induced Electric Fields Does Not Linearly Decrease with Age: A Computational Study of Anatomical Effects in Adults · 2025 · DOI

  • Creating highly realistic scenarios, particularly crucial for neurorehabilitation settings where real-world complexity needs to be replicated.

    Training Cognitive Functions Using DUAL-REHAB, a New Dual-Task Application in MCI and SMC: A Study Protocol of a Randomized Control Trial · 2025 · DOI

  • The study is limited to '90' older adults. The study does not provide information on the long-term effects of the intervention. The study is confined to a specific population (MCI and SMC).

    Training Cognitive Functions Using DUAL-REHAB, a New Dual-Task Application in MCI and SMC: A Study Protocol of a Randomized Control Trial · 2025 · DOI

  • The relationships among structural connectivity, functional connectivity, and age in macaques have not yet been fully investigated. There is a lack of understanding of age-related changes in resting-state networks in macaque monkeys.

    Age-related alterations in functional and structural networks in the brain in macaque monkeys · 2025 · DOI

  • The change trend of the cortical electric field and the determinants of the induced electric field in adults are not well understood. The degree of influence of global and local anatomical parameters on the electric field is not well understood. The relationship between cortical electric field amplitude and age is not well understood.

    Amplitude of Intracranial Induced Electric Fields Does Not Linearly Decrease with Age: A Computational Study of Anatomical Effects in Adults · 2025 · DOI

  • Cortico-white matter functional coupling integrates neuronal activity with axonal conduction, yet its natural trajectory across the AD spectrum and ability to be modulated by repetitive transcranial magnetic stimulation (rTMS) remain unclear.

    Cortico-white Matter Functional Coupling as a Biomarker of Alzheimer’s Disease Progression and rTMS Therapeutic Efficacy · 2026 · DOI

  • Individual differences in cognitive abilities vary widely, yet the structural brain features supporting these differences remain poorly understood.

    Inferring continuous cognitive traits from limited neuroimaging data using pairwise convolutional neural networks · 2026

  • However, the dynamic trajectory of functional network alterations in MS remains unclear.

    Hidden Markov Modeling Reveals Altered Functional Network Dynamics in Multiple Sclerosis · 2026 · DOI

  • Despite this, little is known about the foundations of cerebellar functional organisation in early life.

    Early development of cerebellar functional connectivity · 2026 · DOI

  • These developmental changes may contribute to age-related differences in the association between cannabis use and large-scale functional network organisation, yet this association remains incompletely characterised.

    Longitudinal fMRI reveals altered developmental trajectories of functional network organisation associated with adolescent cannabis use · 2026 · DOI

  • Population-level structural connectomes provide common references for studying brain organization, yet their adequacy for representing individual brains remains unclear.

    When are population connectome harmonics adequate representations of individual brains? · 2026 · DOI

  • Classical covariance methods are not suitable for unordered relationships. Vectorizing a network does not resolve the issue of how to define a covariance model on the relationships themselves. Treating all connections independently discards scientific structure.

    Covariance Kernels on Unordered Pair Spaces: Theory and Applications to Network-Valued Data · 2026 · DOI

  • Investigate the effects of ATD on 5-HT signaling in female participants, - Examine the relationship between TPH2 genotype and 5-HT signaling in other populations, - Develop personalized treatment strategies based on genetic variations, - Explore the neural mechanisms underlying emotional dysregulation in anxiety and stress-related…

    State and trait serotonin variations interact to shape the intrinsic connectivity and gradient architecture of the brain – a combined TPH2 genetics and tryptophan depletion study in men · 2026 · DOI

  • Investigating the use of ensemble learning to improve the representation quality. Exploring the application of the proposed method to other psychiatric disorders.

    Decoding cortical folding with deep learning: toward neurodevelopmental biomarkers of psychiatric disorders · 2026 · DOI

  • Small sample size, - Limited to drug-naïve MCI-LB participants, - Education as a proxy of cognitive reserve/brain resilience may not be…

    Dynamic functional connectivity is related to cognitive performance of prodromal Lewy body dementia · 2026 · DOI

  • Investigate the relationship between cognitive performance and brain connectivity dynamics in larger samples, - Examine the effects of medication on brain connectivity dynamics in MCI-LB, - Explore the relationship between education and cognitive reserve/brain resilience…

    Dynamic functional connectivity is related to cognitive performance of prodromal Lewy body dementia · 2026 · DOI

  • A probabilistic treatment of estimated geometry could connect these deterministic bounds to convergence theory for learned embeddings and covariance estimators - Non-Gaussian outcomes and time-varying relational processes would extend the inferential setting - The higher-order construction in Appendix A also suggests analogous theory for relations involving more than two…

    Covariance Kernels on Unordered Pair Spaces: Theory and Applications to Network-Valued Data · 2026 · DOI

  • Investigating the effects of volume-conductance effects and topological distortions caused by subjective thresholding, - Moving beyond traditional single-feature connectivity analyses to characterize high-dimensional spatiotemporal network dynamics, - Exploring the potential dimensional heterogeneity of damage within classic prefrontal regulatory…

    Multiscale EEG network alterations in adolescents with depressive symptoms: static–dynamic connectivity, topological features, and exploratory scalp-level network hubs · 2026 · DOI

  • The study only examined the macaque insula - The study used a limited number of cluster validation methods - The study did not examine the functional organization of the insula…

    Intrinsic functional clustering of the macaque insular cortex · 2024 · DOI

Most-cited papers in Functional Brain Connectivity Studies

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Open questions raised by papers listed on this page include: (1) There is a lack of understanding of the association between obesity and premature pubarche and their effects on brain functional connectivity (“Obesity-Associated Differences in Brain Functional Connectivity in Girls with…”, 2026); (2) Lack of objective neuroimaging biomarkers for identifying neurobiological subtypes (“Edge-centric brain connectomes reveal two molecularly distinct neurobiological…”, 2026); (3) There is a need to understand how individual variations in 5-HT-regulating genetic polymorphisms interact with acute tryptophan depletion to shape brain connectivity and architecture (“State and trait serotonin variations interact to shape the intrinsic…”, 2026); (4) The neural underpinnings of linguistic deficits in patients with Lewy body diseases are not well understood (“Language network disruption in patients with Lewy body diseases”, 2026); (5) There is a need to move beyond traditional single-feature connectivity analyses to characterize high-dimensional spatiotemporal network dynamics (“Multiscale EEG network alterations in adolescents with depressive symptoms:…”, 2026). 1,332 gap statements have been mined from Functional Brain Connectivity Studies papers in our 7.9M-paper local library, which holds 5,620 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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