Alzheimer’s disease (AD) pathology is marked by the deposition of amyloid-β plaques and hyperphosphorylated tau neurofibrillary tangles. This pathology begins years before the first clinical symptoms emerge and progresses through several stages before clinical diagnosis. AD’s pathology alters the brain’s functional connectivity (FC) patterns and these altered FC patterns may serve as imaging markers to diagnose and assess the progression of AD. In this review, we summarize the recent literature investigating connectome alterations across the AD spectrum, spanning preclinical, prodromal, and clinical stages. We identify specific regions and functional connections that are altered across different stages of AD and discuss their relevance to cognition. We also highlight the potential of connectome-based predictive modeling as an individual-specific method in the quest for early diagnosis of AD. The default mode network (DMN) shows significant changes across stages, and its core hubs consistently exhibit reduced connectivity with the medial temporal lobe in association with disease pathology. From a dynamic FC point of view, the flexibility of different networks, especially DMN, was reduced as a result of AD onset and persisted across the stages. These disruptions were also linked to reduced cognitive performance, particularly in domains such as memory and executive function. By bringing together evidence on both disease-specific and stage-specific alterations in FC, this review aims to identify patterns that are most informative for understanding AD progression and their potential for advancing early diagnosis.

Multiple sclerosis (MS), one of the most common neurological causes of disability in young adults, is characterized by cognitive deficits in addition to balance-related symptoms, fatigue, and visual symptoms. Patients have difficulties in different cognitive domains such as memory, learning, executive functions, and attention, especially information processing speed. Current conventional imaging methods are insufficient to elucidate cognitive impairments. Structural alterations in the brain obtained by magnetic resonance imaging (MRI) do not have a high correlation in explaining all cognitive deficits. Therefore, connectivity-based approaches that address brain functions in a more holistic perspective come to the forefront in explaining cognitive functions. The relationship of cognitive deficits with large-scale functional networks through functional connectivity-based approaches via resting-state functional magnetic resonance imaging has begun to be investigated. Although functional connectivity (FC) studies are successful in explaining cognitive functions, the findings are not homogenous. The aim of this review is to analyse the contribution of functional connectivity-based approaches in understanding the clinical-imaging mismatch and to show that cognitive dysfunctions frequently seen in MS patients can only be partially explained by conventional structural imaging techniques. In this respect, this study is a narrative review based on a review of the literature published in the last fifteen years. While the importance of FC in explaining cognitive functions is mentioned, it is also emphasized that the findings of this study may be affected by individual factors such as cognitive reserve.

Patients with minor stroke exhibit slowed processing speed and generalized alterations in functional connectivity involving frontoparietal cortex (FPC). The pattern of connectivity evolves over time. In this study, we examine the relationship of functional connectivity patterns to cognitive performance, to determine neurophysiological underpinnings of improvement, and whether connectivity profiles may be useful in evaluating and predicting longer-term cognitive outcomes. Patients hospitalized with a minor ischemic stroke (NIH Stroke Scale < 10) were neurologically evaluated approximately 1 month following discharge. A battery of neuropsychological tests was administered to assess performance across multiple cognitive domains. Functional connectivity was evaluated using resting state magnetoencephalography (MEG). Repeat evaluations were performed 3-6 months later. The Network Localized Granger Causality framework was used to estimate functional connectivity at each visit. Relationships between functional connectivity and cognitive performance at each visit were assessed using cluster-based permutation tests and mixed effects modeling. Forty-nine patients had available data for both follow-up visits. The average age was 62.4 years; 57% were female; 39% were Black. Mixed effects models indicated significant increases in contralesional frontoparietal beta-band connectivity across visits that corresponded to improved behavioral performance. Early reliance on the contralesional hemisphere was associated with better scores at visit 1, and continued reliance on areas within the ipsilesional hemisphere was associated with poorer performance at visit 2. Specific connectivity profiles are associated with better acute and longer-term cognitive performance and may indicate greater potential for recovery. Further studies are needed to determine if patterns are modifiable.

To investigate alterations in functional connectivity of the mediodorsal thalamic nucleus (MD) in Chronic Insomnia Disorder (CID) patients and their correlations with clinical neuropsychological characteristics. The study enrolled individuals who met the International Classification of Sleep Disorders -Third Edition (ICSD-3) criteria for CID, with the addition of age- and sex-matched healthy controls (HC). Using bilateral Mediodorsal medial magnocellular (MDm) and Mediodorsal lateral parvocellular (MDl) as seeds, whole-brain resting-state functional connectivity (RSFC) was analyzed. Group RSFC differences between CID and HC were compared, followed by correlations with Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scales (SAS) and Self-Rating Depression Scales (SDS) in CID patients. Mediation analyses were conducted to investigate whether RSFC alterations serve as a mediator associated with symptoms of anxiety or depression in CID patients. The study included 50 CID patients and 42 HCs. Patients showed reduced RSFC of the MD with the other subregions of the thalamus, middle frontal gyrus (MFG), lingual gyrus (LING), caudate nucleus (CAU), and cerebellum. The left MDl-right LING connectivity showed a significant negative correlation with SAS scores, and this connectivity significantly mediated the relationship between sleep quality and anxiety in CID patients. Our findings demonstrate that the MD may serves as a critical hub in both sleep-wake regulation and emotional processing networks in CID patients, positioning it as a promising target for personalized neuromodulation therapies aimed at treating CID and its comorbid anxiety.

In the later stages of Parkinson’s disease, patients often manifest levodopa-induced dyskinesia (LID), compromising their quality of life. The pathophysiology underlying LID is poorly understood, and treatment options are limited. To move toward filling this treatment gap, the intrinsic and synaptic changes in striatal spiny projection neurons (SPNs) triggered by the sustained elevation of dopamine (DA) during dyskinesia were characterized using electrophysiological, pharmacological, molecular, and behavioral approaches. Our studies revealed that the intrinsic excitability and functional corticostriatal connectivity of SPNs in dyskinetic mice oscillate between LID on- and off-states in a cell- and state-specific manner. Although triggered by levodopa, these oscillations in SPN properties depended on both dopaminergic and cholinergic signaling. Disrupting M1 muscarinic receptor signaling specifically in indirect pathway SPNs or deleting its downstream signaling partner CalDAG-GEFI blunted the levodopa-induced alterations in functional connectivity, enhanced the motoric benefits of levodopa, and attenuated LID severity.

Altered task-related brain network dynamics and performance consistency in a non-clinical group burdened with childhood trauma.

Sensory processing disorder (SPD) is a neurodevelopmental condition characterized by impaired sensory discrimination and responsivity. Although the causes and neural correlates of SPD remain poorly understood, prenatal influences should be considered, as the prenatal environment is strongly implicated in the progression of neurodevelopmental disorders. One factor hypothesized to promote SPD is perinatal Western‐style diet (WSD) exposure. This study explored the effects of perinatal WSD exposure on the proposed neural correlates of SPD in Japanese macaques. Functional connectivity between sensory and emotional processing areas was assessed at 4 months of age using resting‐state functional magnetic resonance imaging (rs‐fMRI). A machine learning model successfully predicted perinatal diet group based on functional connectivity strengths, indicating that differences in sensory connectivity exist between diet groups. Intra‐somatomotor, visual‐auditory, somatomotor‐auditory, somatomotor‐visual, and intra‐visual network connections demonstrated the greatest differences between groups, with primary motor cortex connectivity being the most impacted. Connections to the amygdala were not major contributors to accurate model performance, but amygdala connectivity, especially to the somatomotor network, may still be a weak driver of model performance. These findings suggest that a proposed predictor of SPD, perinatal WSD exposure, impacts the functional connectivity of sensory processing areas relevant in SPD during early infancy.

Neural correlates of shift work in nurses: Alterations in cortical gyrification and functional connectivity.

Lower cortical gyrification and connectivity in major depressive disorder associated with cognition deficits and neurotransmitter profiles.

Neural Mechanisms Underlying the Depression-reducing Effects of Mindfulness-Based Stress Reduction in University Students: A Rs-fMRI Study.

Social cognitive dysfunction and altered functional connectivity and small-world properties of the social brain network in idiopathic generalized epilepsy.

MIR124 polygenic risk and functional connectivity of the striatum in patients with bipolar disorder: mediation by childhood trauma.

Dynamic alterations in effective functional connectivity in patients with obstructive sleep apnea: Insights from fMRI and electrochemical sensor testing

This study aimed to investigate the alterations in resting-state functional connectivity (rsFC) in patients with cervical spondylotic myelopathy (CSM) using functional near-infrared spectroscopy (fNIRS), and to explore the neuropathological mechanisms underlying these changes. Fifteen CSM patients (JOA score: 12.3 ± 2.1) and 15 age-matched healthy controls (HCs) underwent fNIRS recording during an eyes-open resting state. Hemodynamic signals were acquired from 63 channels covering the prefrontal, parietal, and occipital cortices. Pearson correlation coefficients were calculated for channel-wise time series, and group differences in FC matrices were compared using two-sample t-tests (p < 0.05) with false discovery rate (FDR) correction. CSM patients exhibited significantly enhanced connectivity between the secondary somatosensory cortex and premotor/somatosensory association cortices at the total hemoglobin (HbT) level compared to HCs (frontal eye field-supramarginal gyrus: 0.77220 ± 0.09584 vs. 0.600266 ± 0.141879, FDR p < 0.05). Hyperconnectivity was observed between the right occipital lobe and bilateral prefrontal cortices in CSM patients (left prefrontal-right occipital: 0.18390 ± 0.117860 vs. 0.049514 ± 0.11688, FDR p < 0.05; right prefrontal-right occipital: 0.190342 ± 0.144897 vs. 0.0544925 ± 0.0856284, FDR p < 0.05). Notably, the right occipital lobe showed more pronounced hyperconnectivity with the right dorsolateral prefrontal cortex ( 0.26741 ± 0.11123 vs. 0.02533 ± 0.13632, FDR p < 0.01). This study provides the first fNIRS-based evidence of characteristic functional network changes and compensatory reorganization in CSM patients. The observed hyperconnectivity between the occipital and prefrontal cortices may reflect neuroplastic responses to visual and chronic sensorimotor deficits, while global integration impairments could underlie clinical disabilities. These quantifiable connectivity signatures offer novel targets for monitoring disease progression and evaluating therapeutic interventions.

Objective: To investigate the relationship between alterations in dynamic functional connectivity (dFC) and spatial navigation abilities in individuals with subjective cognitive decline (SCD) across different Traditional Chinese Medicine (TCM) constitutions. Methods: Seventy-five participants with SCD, comprising 34 individuals with balanced constitutions and 41 individuals with biased constitutions, were recruited from the Affiliated Drum Tower Hospital of Nanjing University Medical School between August 2022 and January 2025. The participants underwent TCM constitution assessment, spatial navigation ability testing, and neuropsychological scale evaluation. Additionally, each participant was assessed using 3.0 T resting-state functional magnetic resonance imaging (rs-fMRI) and high-resolution T1-weighted imaging scans. Based on prior research, 20 spatial navigation-related regions of interest (ROIs) were defined. Afterwards, rs-fMRI time series were segmented using a sliding time window approach before calculating the dFC within the spatial navigation brain network. Results: Compared to the balanced constitution group, the biased constitution SCD group showed significantly lower scores on the Mini-Mental State Examination (MMSE) (z=-3.05, P=0.002) and the Auditory Verbal Learning Test (AVLT) measures: immediate recall (z=-2.12, P=0.035), short-delay recall (z=-2.22, P=0.026), long-delay recall (z=-2.88, P=0.004), cued recall (z=-2.91, P=0.004), and recognition (z=-2.20, P=0.028). They also exhibited significantly higher average error distances in ego-allocentric navigation (z=-2.28, P=0.023), egocentric navigation (z=-2.31, P=0.021), and delayed navigation (z=-2.02, P=0.043). Participants with SCD who had a biased constitution also demonstrated significantly reduced dFC between the left parahippocampal gyrus (PHG) and left prefrontal cortex (PFC) (t=2.43), right precuneus and right retrosplenial cortex (RSC) (t=2.96), and left inferior parietal lobule (IPL) and left hippocampus (t=2.42) (all P<0.05, Bonferroni-corrected). Conversely, the dFC was significantly increased between the right PHG and left PFC (t=-2.29, P<0.05, Bonferroni-corrected). Significant correlations were also found in participants with SCD who had biased constitutions: the dFC between the left PHG and left PFC positively correlated with the egocentric navigation average total error (r=0.34, P=0.030) and negatively correlated with the visuospatial memory cognitive domain (r=-0.35, P=0.026); the dFC between the left IPL and left hippocampus negatively correlated with the egocentric navigation average total error (r=-0.32, P=0.043); and the dFC between the right PHG and left PFC positively correlated with the delayed navigation average total error (r=0.33, P=0.037). The area under the ROC curve for the combined differences in cognitive assessments, spatial navigation behavior, and navigation-related brain network dFC was 0.966 in predicting biased constitution versus balanced constitution in participants with SCD. Conclusions: Individuals with SCD and biased constitutions demonstrated poorer spatial navigation ability, possibly due to altered dFC within the spatial navigation brain network. Furthermore, the integrated model based on spatial navigation behaviors and dFC exhibited a high predictive value in distinguishing between individuals with SCD who had balanced and biased constitutions.

Altered resting-state functional connectivity in the sleep-wake circuit in juvenile myoclonic epilepsy: A Seed-based fMRI study.

Electroconvulsive therapy improves functional connectivity of the frontoparietal network and language network in patients with treatment-resistant depression.

Insomnia disorder (ID) frequently coexists with substantial psychiatric comorbidity, particularly anxiety and depression. The neurobiological mechanisms underlying the association between ID and emotional dysregulation remain incompletely understood. The locus coeruleus (LC), a pontine nucleus within the ascending reticular activating system, plays a crucial role in sleep-wake regulation and emotional processing. Here, we acquired simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) data from 37 patients with ID and 30 healthy controls (HCs) during their nocturnal sleep. Group-by-stage interactions in LC-based functional connectivity (FC) were assessed using a linear mixed-effects model. Associations were evaluated between FC patterns and the Pittsburgh sleep quality index (PSQI), the self-rating depression scale (SDS) and the self-rating anxiety scale (SAS). Significant group-by-stage interactions were observed in multiple brain regions, including the cingulate cortex, right insular cortex, left temporal cortex and left insular cortex. Post hoc analyses revealed that patients with ID exhibited significantly enhanced FC between the LC and cingulate cortex during N2 sleep compared to HCs (p = 0.023). In the pooled sample, N2-specific LC-cingulate cortex connectivity strength demonstrated significant positive correlations with both SDS scores (r = 0.337, p = 0.018) and PSQI scores (r = 0.401, p = 0.003). In conclusion, the observed alterations in LC-cingulate cortex FC during N2 sleep suggest a distinct neural circuit that may underlie the dysregulation of emotional processing in ID. These findings may provide insights into neurobiological mechanisms in ID.

Cognitive and behavioral deficits in Alzheimer’s disease (AD) and frontotemporal dementia (FTD) arise alongside gray matter atrophy and altered functional connectivity, yet the structure-function relationship across the dementia spectrum remains unclear. Here we combine structural and functional MRI from 221 patients—AD (n = 82), behavioral variant FTD (n = 41), corticobasal syndrome (n = 27), and nonfluent (n = 34) or semantic (n = 37) variant primary progressive aphasia—and 100 cognitively normal individuals. Partial least-squares regression reveals three structure–function components. Component 1 links cumulative atrophy to sensorimotor hypo-connectivity and hyper-connectivity in association cortical and subcortical brain regions. Components 2 and 3 tie focal, syndrome-specific atrophy to peri-lesional hypo-connectivity and distal hyper-connectivity. Structural and functional component scores explain 34% of the variance in global and domain-specific cognitive deficits on average. The functional connectivity changes reflect alterations of intrinsic activity gradients. Eigenmode analysis shows that atrophy relates to reduced gradient amplitudes and narrowed phase angles between gradients, offering a mechanistic account of network collapse in neurodegeneration.

Frequency-specific alterations in low-frequency functional connectivity in children with ADHD.