Alterations in Dynamic Functional Connectivity in Individuals With Subjective Cognitive Decline

Brain connectivity is highly dynamic, but functional connectivity (FC) studies using resting-state functional magnetic resonance imaging (rs-fMRI) assume it to be static. This study assessed differences in dynamic FC between young healthy adults (YH) and elderly healthy adults (EH) compared to static FC. Using rs-fMRI data from 12 YH and 31 EH, FC was assessed in six functional regions (subcortical, auditory [AUD], sensorimotor [SM], visuospatial [VS], cognitive control [CC], and default mode network [DMN]). Static FC was calculated as Fisher's z-transformed correlation coefficient. The sliding time window correlation (window size 30s, step size 3s) was applied for dynamic FC, and the standard deviation across sliding windows was calculated. Differences in static and dynamic FC between EH and YH were calculated and compared by region. EH showed decreased static FC in the subcortical, CC, and DMN regions (FDR corrected p=0.0013; 74 regions), with no regions showing static FC higher than that in YH. EH showed increased dynamic FC in the subcortical, CC, and DMN regions, whereas decreased dynamic FC in CC and DMN regions (p<0.01). However, the regions showing differences between EH and YH did not overlap between static and dynamic FC. Dynamic FC exhibited differences from static FC in EH and YH, mainly in regions involved in cognitive control and the DMN. Altered dynamic FC demonstrated both qualitatively and quantitatively distinct patterns of transient brain activity and needs to be studied as an imaging biomarker in the aging process.

Background: Neuroanatomical variations are increasingly recognized for their role in influencing cognitive functions, particularly in individuals with subjective cognitive decline (SCD). Structural differences in gray matter (GM) and white matter (WM) volumes, as well as cortical thickness, may underlie the cognitive impairments observed in SCD. Understanding these neuroanatomical changes is crucial for early detection and intervention strategies in cognitive decline. Objective: This study aimed to investigate the neuroanatomical variations between individuals with SCD and healthy controls and to examine the impact of these variations on cognitive functions. Methods: The study was conducted at the Faculty of Rehabilitation Sciences, Lahore University of Biological and Applied Sciences, Pakistan. A total of 42 participants were included, with 21 individuals in the SCD group and 21 in the control group. Participants were recruited through advertisements and referrals, and inclusion criteria for the SCD group included individuals aged 60 and above with self-reported cognitive concerns but no objective impairment on neuropsychological tests. Neuroimaging data were acquired using a 3.0 Tesla MRI scanner, and high-resolution T1-weighted images were analyzed using Statistical Parametric Mapping (SPM) software version 12 and FreeSurfer software. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), Trail Making Test (TMT) Parts A and B, California Verbal Learning Test (CVLT), and Boston Naming Test (BNT). Data analysis was performed using SPSS version 25, with independent t-tests and chi-square tests to compare groups and ANCOVA to adjust for confounders. Effect sizes were calculated using Cohen’s d. Results: Significant differences were observed between the SCD and control groups in several neuroanatomical measures. Individuals with SCD had reduced GM volume in the anterior cingulate cortex (R, p=0.018; L, p=0.025), midcingulate cortex (R, p=0.037), and middle frontal gyrus (L, p=0.030). Significant reductions in WM volume were also found in the inferior frontal gyrus (L, p=0.028) and postcentral gyrus (L, p=0.047). Cortical thickness was significantly reduced in the inferior temporal gyrus (L, p=0.0002; Cohen’s d=1.06), entorhinal cortex (L, p=0.008; Cohen’s d=1.03), and middle temporal gyrus (R, p=0.0004; Cohen’s d=1.02). Cognitive assessments revealed that the SCD group had significantly lower scores on the MMSE (p=0.294, d=0.33), GDS-15 (p=0.001, d=-1.08), and subjective cognitive complaints from patients (p&lt;0.001, d=-2.89). Conclusion: The study found significant neuroanatomical differences between individuals with SCD and healthy controls, particularly in GM and WM volumes and cortical thickness. These structural variations were associated with cognitive impairments observed in the SCD group, underscoring the importance of early detection and targeted interventions. Future research should focus on longitudinal studies and the integration of biomarkers to enhance the understanding of neuroanatomical changes in cognitive decline. Keywords: Neuroanatomical Variations, Subjective Cognitive Decline, Gray Matter Volume, White Matter Volume, Cortical Thickness, Cognitive Functions, MRI, Neuroimaging, Early Detection, Cognitive Decline.

Reconfigurations of dynamic functional network connectivity after 1HZ repetitive transcranial magnetic stimulation in insomnia disorder.

The specific topological changes in dynamic functional networks and their role in cervical spondylotic myelopathy (CSM) brain function reorganization remain unclear. This study aimed to investigate the dynamic functional connection (dFC) of patients with CSM, focusing on the temporal characteristics of the functional connection state patterns and the variability of network topological organization. Eighty-eight patients with CSM and 77 healthy controls (HCs) were recruited for resting-state functional magnetic resonance imaging. We applied the sliding time window analysis method and K-means clustering analysis to capture the dFC variability patterns of the two groups. The graph-theoretical approach was used to investigate the variance in the topological organization of whole-brain functional networks. All participants showed four types of dynamic functional connection states. The mean dwell time in state 2 was significantly different between the two groups. Particularly, the mean dwell time in state 2 was significantly longer in the CSM group than in the healthy control group. Among the four states, switching of relative brain networks mainly included the executive control network (ECN), salience network (SN), default mode network (DMN), language network (LN), visual network (VN), auditory network (AN), precuneus network (PN), and sensorimotor network (SMN). Additionally, the topological properties of the dynamic network were variable in patients with CSM. Dynamic functional connection states may offer new insights into intrinsic functional activities in CSM brain networks. The variance of topological organization may suggest instability of the brain networks in patients with CSM.

Subjective cognitive decline (SCD) is a high-risk population in the preclinical stage of Alzheimer's disease (AD), and olfactory dysfunction is a risk factor for dementia progression. The present study aimed to explore the patterns of functional connectivity (FC) changes in the olfactory neural circuits during olfactory stimulation in SCD subjects. A total of 56 SCD subjects and 56 normal controls (NCs) were included. All subjects were assessed with a cognitive scale, an olfactory behavior test, and olfactory task-based functional magnetic resonance imaging scanning. The FC differences in olfactory neural circuits between the two groups were analyzed by the generalized psychophysiological interaction. Additionally, we calculated and compared the activation of brain regions within the olfactory neural circuits during odor stimulation, the volumetric differences in brain regions showing FC differences between groups, and the correlations between neuroimaging indicators and olfactory behavioral and cognitive scale scores. During odor stimulation, the FC between the bilateral primary olfactory cortex (bPOC) and the right hippocampus in the SCD group was significantly reduced; while the FC between the right hippocampus and the right frontal cortex was significantly increased in the SCD group. The bPOC of all subjects showed significant activation, but no significant difference in activation between groups was found. No significant differences were observed in the volume of the brain regions within the olfactory neural circuits or in olfactory behavior between groups. The volume of the bPOC and right frontal cortex was significantly positively correlated with olfactory identification, and the volume of the right frontal cortex and right hippocampus was significantly correlated with cognitive functions. Furthermore, a significant correlation between the activation of bPOC and the olfactory threshold was found in the whole cohort. These results suggested that while the structure of the olfactory neural circuits and olfactory behavior in SCD subjects remained stable, there were significant changes observed in the FC of the olfactory neural circuits (specifically, the POC-hippocampus-frontal cortex neural circuits) during odor stimulation. These findings highlight the potential of FC alterations as sensitive imaging markers for identifying high-risk individuals in the early stage of AD.

BackgroundExcessive daytime sleepiness (EDS) is a frequent nonmotor symptoms of Parkinson’s disease (PD), which seriously affects the quality of life of PD patients and exacerbates other nonmotor symptoms. Previous studies have used static analyses of these resting-state functional magnetic resonance imaging (rs-fMRI) data were measured under the assumption that the intrinsic fluctuations during MRI scans are stationary. However, dynamic functional network connectivity (dFNC) analysis captures time-varying connectivity over short time scales and may reveal complex functional tissues in the brain.PurposeTo identify dynamic functional connectivity characteristics in PD-EDS patients in order to explain the underlying neuropathological mechanisms.MethodsBased on rs-fMRI data from 16 PD patients with EDS and 41 PD patients without EDS, we applied the sliding window approach, k-means clustering and independent component analysis to estimate the inherent dynamic connectivity states associated with EDS in PD patients and investigated the differences between groups. Furthermore, to assess the correlations between the altered temporal properties and the Epworth sleepiness scale (ESS) scores.ResultsWe found four distinct functional connectivity states in PD patients. The patients in the PD-EDS group showed increased fractional time and mean dwell time in state IV, which was characterized by strong connectivity in the sensorimotor (SMN) and visual (VIS) networks, and reduced fractional time in state I, which was characterized by strong positive connectivity intranetwork of the default mode network (DMN) and VIS, while negative connectivity internetwork between the DMN and VIS. Moreover, the ESS scores were positively correlated with fraction time in state IV.ConclusionOur results indicated that the strong connectivity within and between the SMN and VIS was characteristic of EDS in PD patients, which may be a potential marker of pathophysiological features related to EDS in PD patients.

Cerebral small vessel disease (CSVD) is a common disease that seriously endangers people’s health, and is easily overlooked by both patients and clinicians due to its near-silent onset. Dynamic functional connectivity (DFC) is a new concept focusing on the dynamic features and patterns of brain networks that represents a powerful tool for gaining novel insight into neurological diseases. To assess alterations in DFC in CSVD patients, and the correlation of DFC with cognitive function. We enrolled 35 CSVD patients and 31 normal control subjects (NC). Resting-state functional MRI (rs-fMRI) with a sliding-window approach and k-means clustering based on independent component analysis (ICA) was used to evaluate DFC. The temporal properties of fractional windows and the mean dwell time in each state, as well as the number of transitions between each pair of DFC states, were calculated. Additionally, we assessed the functional connectivity (FC) strength of the dynamic states and the associations of altered neuroimaging measures with cognitive performance. A dynamic analysis of all included subjects suggested four distinct functional connectivity states. Compared with the NC group, the CSVD group had more fractional windows and longer mean dwell times in state 4 characterized by sparse FC both inter-network and intra-networks. Additionally, the CSVD group had a reduced number of windows and shorter mean dwell times compared to the NC group in state 3 characterized by highly positive FC between the somatomotor and visual networks, and negative FC in the basal ganglia and somatomotor and visual networks. The number of transitions between state 2 and state 3 and between state 3 and state 4 was significantly reduced in the CSVD group compared to the NC group. Moreover, there was a significant difference in the FC strength between the two groups, and the altered temporal properties of DFC were significantly related to cognitive performance. Our study indicated that CSVD is characterized by altered temporal properties in DFC that may be sensitive neuroimaging biomarkers for early disease identification. Further study of DFC alterations could help us to better understand the progressive dysfunction of networks in CSVD patients.

Subjective cognitive decline (SCD), as expressed by older adults, is associated with negative affect, which, in turn, is a likely risk factor for Alzheimer’s Disease (AD). This study assessed the associations between negative affective burden, cognitive functioning, and functional connectivity in networks vulnerable to AD in the context of SCD. Older participants (60–90 years) with SCD (n = 51) and healthy controls (n = 50) were investigated in a cross-sectional study. Subclinical negative affective burden, quantified through a composite of self-reported negative affective factors, was related to cognitive functioning (self-perceived and objective) and functional connectivity. Seed-to-voxel analyses were carried out in default mode network (DMN) and salience network (SAL) nodes using resting-state functional magnetic resonance imaging. Greater negative affective burden was associated with lower self-perceived cognitive functioning and lower between-network functional connectivity of DMN and SAL nodes in the total sample. In addition, there was a significant moderation of SCD status. Greater negative affective burden related to higher functional connectivity within DMN (posterior cingulate-to-precuneus) and within SAL (anterior cingulate-to-insula) nodes in the SCD group, whereas in controls the inverse association was found. We show that negative affective burden is associated with functional brain alterations in older adults, regardless of SCD status. Specifically in the SCD phenotype, greater negative affective burden relates to higher functional connectivity within brain networks vulnerable to AD. Our findings imply that negative affective burden should be considered a potentially modifiable target for early intervention.

Subjective cognitive decline (SCD) serves as an initial symptom of preclinical Alzheimer’s disease (AD). The accumulation of amyloid-beta (Aβ) is acknowledged as a critical risk factor for the eventual progression to mild cognitive impairment or dementia in individuals with SCD, highlighting the necessity for early detection and intervention. Previous studies have identified the retina and choriocapillaris as potential biomarkers for AD; however, these investigations have not thoroughly examined large and medium-sized choroidal vessels. Ultra-wide swept-source optical coherence tomography angiography (SS-OCTA), an innovative noninvasive imaging modality, facilitates rapid and precise quantitative assessment of retinal and choroidal boundaries and vasculature through dynamic scanning, encompassing large and medium-sized choroidal vessels. This study aims to characterize the outer retinal and choroidal vasculature and structure in individuals with SCD, examine the correlation between altered choroidal vasculature parameters and amyloid burden, and the presence of the apolipoprotein E (APOE) ε4 allele in SCD participants, to identify potential ocular biomarkers for high-risk SCD screening. In this study, 57 individuals with SCD and 45 matched normal controls were enrolled. Ultra-wide SS-OCTA was employed to assess the thickness of the outer retina and choroid and the blood flow within the choriocapillaris and large, medium-sized choroidal vessels. 18F-Florbetapir positron emission tomography scans were performed to classify amyloid-positive-SCD (Aβ + SCD) and amyloid-negative-SCD (Aβ-SCD) groups. Plasma Aβ42/40 and APOE ε4 genotypes were also measured. Compared with normal controls, individuals with SCD exhibited a significant increase in the choroidal vessel index and a reduction in outer retinal thickness. The Aβ + SCD group demonstrated an elevated choriocapillaris flow area relative to the Aβ- SCD group. Moreover, a negative correlation was observed between the choriocapillaris flow area and plasma Aβ42/40 levels in the SCD cohort. Among SCD participants, APOE ε4 carriers displayed increased choriocapillaris flow area and choroidal vessel volume compared to APOE ε4 non-carriers. Our findings provide intriguing insights into the relationship between amyloid pathology and changes in the choriocapillaris flow area. The choroid may serve as a potential biomarker for screening Aβ + SCD.

The pathogenesis of autism spectrum disorder (ASD) remains unclear. Diagnosis relies on symptoms and relevant scales, which are highly subjective. Moreover, most diagnoses are made after the age of 3, delaying treatment opportunities. This study aimed to explore dynamic functional network connectivity (dFNC) in toddlers with ASD aged 1-3 years, to identify group-level differences in dynamic functional connectivity (FC) patterns and investigate their associations with autistic symptoms, with the goal of providing preliminary neuroimaging insights into the neural mechanisms underlying ASD during this critical developmental window. Magnetic resonance imaging (MRI) data of 41 toddlers diagnosed with ASD and 23 age- and sex-matched normal development control (NC) individuals were collected. We examined group differences in dFNC properties, including temporal characteristics of brain states, mean dwell time (MDT), state occurrence rate (OR), and state transition frequency. Correlation analyses were performed to assess the relationships between these dFNC metrics and the severity of autistic symptoms. Compared with the NC group, toddlers with ASD spent more time in a brain state characterized by globally weak connectivity and a notable lack of between-network functional connectivity, with a significantly higher OR and nominally longer MDT. They also showed a nominally reduced MDT in a brain state marked by strong within-network connectivity and enhanced modular organization across multiple functional networks. Exploratory correlation analyses between autism metrics and dFC measures suggested several nominal associations (uncorrected p < 0.05). Toddlers with ASD exhibit abnormal dFNC patterns, characterized by altered temporal properties of brain states and disrupted state-related connectivity profiles. These results provide empirical evidence for altered dynamic brain organization in early ASD, contributing to a better understanding of its neural underpinnings during this critical developmental window.

This study aimed to clarify the independent and joint associations of loneliness and social isolation with subjective cognitive decline (SCD) among perimenopausal women. This cross-sectional study was conducted between March and September 2024 and comprised 903 perimenopausal women. Subjective perceived loneliness, objective social isolation, and severity of SCD were measured using a set of self-reported online questionnaires. Latent class analysis was employed to determine the high-risk SCD groups among perimenopausal women, and restricted cubic spline model and logistic regression models were further utilized to investigate the independent and joint associations of loneliness and social isolation with SCD. The mean SCD score across all participants was 3.77 (SD=2.99). Latent class analysis categorized the participants into a "mild SCD group" (47.8%) and "severe SCD group" (52.2%). Logistic regression analysis revealed that both loneliness and social isolation were independently associated with SCD. Notably, joint analysis revealed that compared with participants without loneliness and social isolation, those with moderate to severe loneliness and social isolation exhibited the highest odds of severe SCD. Furthermore, significant additive and multiplicative interactions were observed between moderate to severe loneliness and social isolation. In perimenopausal populations, loneliness and social isolation were not only independently associated with SCD but also exhibited a joint relationship. These findings offer deeper insights into understanding the relationship between social connections and SCD, and provide empirical evidence for developing psychosocial interventions aimed at preserving cognitive health in perimenopausal women.

Sleep problems are very prevalent in older adults, especially in those at risk for dementia. But the relationships between sleep parameters and subjective or objective cognitive decline are still inconclusive. The study aimed to investigate the self-reported and objectively measured sleep characteristics in older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). This study adopted a cross-sectional design. We included older adults with SCD or MCI. Sleep quality was measured separately by the Pittsburgh sleep quality index (PSQI) and ActiGraph. Participants with SCD were divided into low, moderate, and high levels of SCD groups. Independent samples T-tests, one-way ANOVA, or nonparametric tests were used to compare the sleep parameters across groups. Covariance analyses were also performed to control the covariates. Around half of the participants (45.9%) reported poor sleep quality (PSQI＜7), and 71.3% of participants slept less than 7 hours per night, as measured by ActiGraph. Participants with MCI showed shorter time in bed (TIB) (p＜0.05), a tendency of shorter total sleep time (TST) at night (p = 0.074) and for each 24-hour cycle (p = 0.069), compared to those with SCD. The high SCD group reported the highest PSQI total score and longest sleep latency than all the other three groups (p＜0.05). Both the MCI and high SCD groups had shorter TIB and TST for each 24-hour cycle than the low or moderate SCD groups. Besides, participants with multiple-domain SCD reported poorer sleep quality than those with single-domain SCD (p＜0.05). Sleep dysregulation is prevalent in older adults with a risk for dementia. Our findings revealed that objectively measured sleep duration might be an early sign of MCI. Individuals with high levels of SCD demonstrated poorerself-perceived sleep quality and deserved more attention. Improving sleep quality might be a potential target to prevent cognitive decline for people with a risk for dementia.

Previous studies reported abnormally increased and/or decreased blood oxygen level-dependent (BOLD) activations during functional tasks in subjective cognitive decline (SCD). The neurophysiological basis underlying these functional aberrations remains debated. This study aims to investigate vascular and metabolic responses and their dependence on cognitive processing loads during functional tasks in SCD. Twenty-one SCD and 18 control subjects performed parametric N-back working-memory tasks during MRI scans. Task-evoked percentage changes (denoted as δ) in cerebral blood volume (δCBV), cerebral blood flow (δCBF), BOLD signal (δBOLD) and cerebral metabolic rate of oxygen (δCMRO2) were evaluated. In the frontal lobe, trends of decreased δCBV, δCBF and δCMRO2 and increased δBOLD were observed in SCD compared with control subjects under lower loads, and these trends increased to significant differences under the 3-back load. δCBF was significantly correlated with δCMRO2 in controls, but not in SCD subjects. As N-back loads increased, the differences between SCD and control subjects in δCBF and δCMRO2 tended to enlarge. In the parietal lobe, no significant between-group difference was observed. Our findings suggested that impaired vascular and metabolic responses to functional tasks occurred in the frontal lobe of SCD, which contributed to unusual BOLD hyperactivation and was modulated by cognitive processing loads.

BackgroundNeuropsychologically intact older adults who report experiencing subjective cognitive decline (SCD) likely draw on daily experiences of cognitive difficulties as an indicator of worsening cognitive functioning. Specifically, the frequency of problems (e.g., memory lapses, difficulty planning) and/or the degree that these problems interfere with their daily activities may play a role in their perception of cognitive changes. The current study examined differences in daily cognitive difficulties in older adults without SCD compared to those with SCD or MCI.MethodParticipants (n=212, Mage=76.97 years, range: 70‐90, 65% female, 50% White) completed a battery of objective cognitive performance tasks, psychosocial questionnaires, and they self‐reported experience of and interference from cognitive difficulties each day for 14 days (via smartphones). Fifty‐seven participants were classified as having mild cognitive impairment (MCI) using the Jak, Bondi (2009) criteria. One hundred and three participants not classified as MCI were classified as SCD as they reported their memory functioning worsening in the past 5 years. The remaining 52 participants with no SCD were normal controls. Generalized linear modeling was used to predict total number of and average interference from memory lapses and general thinking problems from daily reports.ResultAfter accounting for age, sex, race/ethnicity, education, and depressive symptoms, cognitively normal participants with SCD and those with MCI reported significantly more everyday cognitive difficulties compared to cognitively normal participants without SCD (Figures 1‐3). The MCI and SCD groups did not differ from each other (p’s&gt;.07). For retrospective memory lapses and general thinking problems, normal controls reported significantly lower interference than participants with SCD and those with MCI (p’s&gt;.02; Figures 5 and 6). For prospective memory lapses, only participants with MCI reported significantly higher interference than normal controls (p=.01; Figure 4).ConclusionCompared to participants without SCD, participants with SCD and those with MCI reported more frequent everyday cognitive problems and that problems were more likely to interfere in daily activities. Everyday cognitive difficulties may differentiate those individuals more likely to develop functional impairments related to declining cognition. Difficulties meeting daily cognitive demands has the potential to interfere with the ability of older adults to safely live independently.

Tinnitus severity is related to changes in functional connectivity between precuneus and inferior temporal gyrus.