Functional Connectivity In Older Adults Research Articles

Stress system dysfunction and changes in brain volume and functional connectivity in older adults with subclinical depressive symptoms

AbstractBackgroundSubclinical depressive symptoms are associated with increased risk of Alzheimer’s disease (AD). This link could be related to stress system dysfunction, known to occur in both depression and AD, and to depend notably on the hippocampus which is particularly sensitive to AD. We aimed at investigating the links between levels of blood stress markers and changes in brain regions involved in the stress response in older adults with subclinical depressive symptoms.MethodCognitively unimpaired older adults with (DepS; n = 73) or without (NoDepS; n = 58) subclinical depressive symptoms (defined using the 15‐item version of the Geriatric Depression Scale), from the baseline data of the Age‐Well trial (NCT02977819) were included. For each participant, levels of cortisol, epinephrine and norepinephrine were obtained from blood sampling. Moreover, the functional connectivity (FC) between, and the gray matter (GM) volume of, the hypothalamus, hippocampus and hippocampal subfields were extracted from resting‐state functional, and structural T1‐weighted, MRI. Levels of blood stress markers and neuroimaging measures were compared between groups. Regression analyses were then conducted between levels of blood markers and brain measures. Analyses were corrected for age, sex, education and anxiety symptoms with statistical significance set to p<0.05.ResultHigher blood epinephrine level (p<0.024), and FC between the hypothalamus and the CA1 hippocampal subfield (p<0.040), was found in DepS compared to NoDepS (Fig.1). This higher epinephrine level was associated with greater FC between the hypothalamus and the CA1 (p<0.007) and Subiculum (p<0.013) subfields (Fig.2). Lower GM volume in the CA1 (p<0.008) and DG/CA2‐3‐4 (p<0.013) subfields was also found in the DepS group (Fig.3), but was not associated with epinephrine level. No significant between‐group difference in blood cortisol and norepinephrine levels was observed.ConclusionSubclinical depressive symptoms in aging are associated with higher blood epinephrine level related to greater FC between the hypothalamus and hippocampal subfields (CA1 and Subiculum) – suggesting an increased sympathetic nervous system activity. They are also associated with GM atrophy in specific hippocampal subfields, including the CA1 that is sensitive to AD. These two distinct mechanisms at this preclinical stage of depression may at least partly explain that depression is a risk factor for AD.

Heart Rate Variability during Slow Wave Sleep is Linked to Resting‐state Functional Connectivity in the Central Autonomic Network among Older Adults ‘at‐risk’ of Dementia

AbstractBackgroundReduced heart rate variability (HRV) can be an early sign of autonomic dysfunction in neurodegenerative diseases, and may be related to brain dysfunction in the central autonomic network (CAN). As yet, such autonomic dysfunction has not been examined during sleep – which is an ideal physiological state to study brain‐heart interaction as both the central and peripheral nervous systems behave differently compared to during wakefulness. Therefore, we aimed to examine whether nocturnal HRV, especially slow wave sleep (SWS), is associated with CAN functional connectivity in older adults ‘at‐risk’ of dementia.MethodOlder adults (n = 78; age range = 50‐88 years; 64% female) attending a memory clinic for cognitive concerns underwent resting‐state functional magnetic resonance imaging and an overnight polysomnography. From these, CAN functional connectivity strength and HRV data during sleep were derived, respectively. High‐frequency heart rate variability (HF‐HRV) was extracted to index parasympathetic activity during distinct periods of sleep, including SWS as well as secondary outcomes of non‐rapid eye movement sleep, wake after sleep onset, and rapid eye movement sleep. General linear models were used to examine associations between CAN functional connectivity and HF‐HRV.ResultAnalyses revealed that increased HF‐HRV during SWS was associated with stronger functional connectivity (F = 3.98, p = 0.022) in two core brain regions within the CAN, the right anterior insular and posterior midcingulate cortex, as well as stronger functional connectivity (F = 6.21, p = 0.005) between broader CAN brain regions – the right amygdala with three sub‐nuclei of the thalamus. There were no significant associations between HF‐HRV and CAN functional connectivity during wake after sleep onset or rapid eye movement sleep.ConclusionThese findings show that in older adults ‘at‐risk’ of dementia, parasympathetic regulation during SWS is uniquely linked to differential functional connectivity within both core and broader CAN brain regions. It is possible that dysfunctional brain‐heart interactions manifest primarily during this specific period of sleep known for its role in memory and metabolic clearance. Further studies elucidating the pathophysiology and directionality of this relationship should be conducted to determine if HRV drives neurodegeneration, or if brain degeneration within the CAN promotes aberrant HRV.

Resting‐State Connectivity Changes in Older Adults with Sleep Disturbance

AbstractBackgroundSleep and related disorders could lead to changes in various brain network connectivities, but little is known about the role of Aβ burden—a key Alzheimer’s disease (AD) biomarker—in the relationship between sleep disturbance and altered functional connectivity in older adults. This study examined the association between sleep disturbance, Aβ positivity, and with‐in and between resting‐state functional connectivity networks using a large‐scale dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).MethodSample was consisted of 413 individuals (mean age 76.56±7.20; 57.5% cognitively normal, 30.3% mild cognitive impairment, and 12.1% AD) who had completed sleep measures (Neuropsychiatric Inventory), CSF‐Aβ42 data, and resting‐state fMRI scans at baseline. Functional connectivity within Salience (SN), Default Mode (DMN) and Frontal Parietal networks (FPN) were compared between participants with sleep disturbance versus without sleep disturbance. The interaction between Aβ positivity and sleep disturbance were evaluated controlling for age, diagnosis status, gender, sedatives and hypnotics use, and hypertension.ResultSleep disturbance was associated with reduced connectivity in the SN (β = 0.04, P = 0.006) but not with DMN or FPN. Additionally, sleep disturbance interacted significantly with Aβ positivity in altered with‐in connectivity of SN (β = 0.10, P = 0.003), DMN (β = 0.07, P = 0.0048), and FPN (β = 0.09, P = 0.03) networks.ConclusionSleep disturbance may lead to altered connectivity in the SN and further change various within and between functional networks in the presence of amyloid burden.

Heart rate variability during slow wave sleep is linked to functional connectivity in the central autonomic network.

Reduced heart rate variability can be an early sign of autonomic dysfunction in neurodegenerative diseases and may be related to brain dysfunction in the central autonomic network. As yet, such autonomic dysfunction has not been examined during sleep-which is an ideal physiological state to study brain-heart interaction as both the central and peripheral nervous systems behave differently compared to during wakefulness. Therefore, the primary aim of the current study was to examine whether heart rate variability during nocturnal sleep, specifically slow wave (deep) sleep, is associated with central autonomic network functional connectivity in older adults 'at-risk' of dementia. Older adults (n = 78; age range = 50-88 years; 64% female) attending a memory clinic for cognitive concerns underwent resting-state functional magnetic resonance imaging and an overnight polysomnography. From these, central autonomic network functional connectivity strength and heart rate variability data during sleep were derived, respectively. High-frequency heart rate variability was extracted to index parasympathetic activity during distinct periods of sleep, including slow wave sleep as well as secondary outcomes of non-rapid eye movement sleep, wake after sleep onset, and rapid eye movement sleep. General linear models were used to examine associations between central autonomic network functional connectivity and high-frequency heart rate variability. Analyses revealed that increased high-frequency heart rate variability during slow wave sleep was associated with stronger functional connectivity (F = 3.98, P = 0.022) in two core brain regions within the central autonomic network, the right anterior insular and posterior midcingulate cortex, as well as stronger functional connectivity (F = 6.21, P = 0.005) between broader central autonomic network brain regions-the right amygdala with three sub-nuclei of the thalamus. There were no significant associations between high-frequency heart rate variability and central autonomic network connectivity during wake after sleep onset or rapid eye movement sleep. These findings show that in older adults 'at-risk' of dementia, parasympathetic regulation during slow wave sleep is uniquely linked to differential functional connectivity within both core and broader central autonomic network brain regions. It is possible that dysfunctional brain-heart interactions manifest primarily during this specific period of sleep known for its role in memory and metabolic clearance. Further studies elucidating the pathophysiology and directionality of this relationship should be conducted to determine if heart rate variability drives neurodegeneration, or if brain degeneration within the central autonomic network promotes aberrant heart rate variability.

Functional connectivity in older adults-the effect of cerebral small vessel disease.

Ageing is associated with functional reorganization that is mainly characterized by declining functional connectivity due to general neurodegeneration and increasing incidence of disease. Functional connectivity has been studied across the lifespan; however, there is a paucity of research within the older groups (≥75 years) where neurodegeneration and disease prevalence are at its highest. In this cross-sectional study, we investigated associations between age and functional connectivity and the influence of cerebral small vessel disease (CSVD)-a common age-related morbidity-in 167 community-dwelling older adults aged 75-91 years (mean = 80.3 ± 3.8). Resting-state functional MRI was used to determine functional connectivity within ten standard networks and calculate the whole-brain graph theoretical measures global efficiency and clustering coefficient. CSVD features included white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and atrophy that were assessed in each individual and a composite score was calculated. Both main and interaction effects (age*CSVD features) on functional connectivity were studied. We found stable levels of functional connectivity across the age range. CSVD was not associated with functional connectivity measures. To conclude, our data show that the functional architecture of the brain is relatively unchanged after 75 years of age and not differentially affected by individual levels of vascular pathology.

Combined Cognitive Training and Vortioxetine Mitigates Age-Related Declines in Functional Brain Network Integrity

ObjectiveAge-related cognitive decline is common and potentially modifiable with cognitive training. Combining cognitive training with pro-cognitive medication offers an opportunity to modify brain networks to mitigate age-related cognitive decline. We tested the hypothesis that the efficacy of cognitive training could be amplified by combining it with vortioxetine, a pro-cognitive and pro-neuroplastic multimodal antidepressant. MethodsWe evaluated the effects of 6 months of computerized cognitive training plus vortioxetine (versus placebo) on resting state functional connectivity in older adults (age 65+) with age-related cognitive decline. We first evaluated the association of functional connectivity with age and cognitive performance (N = 66). Then we compared the effects of vortioxetine plus cognitive training versus placebo plus cognitive training on connectivity changes over the training period (n = 20). ResultsAt baseline, greater age was significantly associated with lower within-network strength and network segregation, and poorer cognitive function. Cognitive training plus vortioxetine over 6 months positively impacted the relationship between age to mean network segregation. These effects were not observed in the placebo group. In contrast, vortioxetine did not modify the relationship of age to change in mean within-network strength. Exploratory analyses identified the cingulo-opercular network as the network most affected by cognitive training plus vortioxetine. ConclusionThis preliminary study provides evidence that combining cognitive training with pro-cognitive medication may modulate the effects of aging on functional brain networks. Results indicate that for older adults experiencing age-related cognitive decline, vortioxetine has a potentially beneficial effect on the correspondence between aging and functional brain network segregation. These results await replication in a larger sample.

Plasma NfL predicts default mode network functional connectivity in older adults at higher risk for Alzheimer’s disease

AbstractBackgroundNeurofilament light (NfL) is a measure of neuronal damage and has the potential as a monitoring and prognostic biomarker of Alzheimer’s disease (AD) (Mattsson et al., 2019). Likewise, alterations in default mode network (DMN) functional connectivity (FC) may predict AD progression (Jones et al., 2016). Here, we investigated the relationship between plasma NfL levels and DMN FC along the continuum of AD, and explored whether APOE ε4 status influenced this relationship.MethodResting‐state functional MRI data and blood samples were available for 103 older adults (17 with AD dementia, age: 69.2±6.9; m/f: 8/9; CDR: 0.7±0.3; and 86 without dementia (includes amnestic MCI and control), age: 71.7±7.4; m/f: 21/65; CDR: 0.3±0.2). Plasma NfL was measured using a single‐molecule array (Simoa) assay. We calculated DMN FC using 32 high consensus DMN ROIs from Dworetsky et al. (2021). DMN FC was defined as the average correlation between the mean time‐series of three ROIs labeled as posterior cingulate cortex and those of all the other ROIs. Participants’ APOE status was defined as APOE ε4 carriers (ε3/ε4 or ε4/ε4) and noncarriers (ε3/ε3). Multiple regression was run with DMN FC as the outcome variable, plasma NfL as the predictor, and age and sex as covariates.ResultPlasma NfL levels were higher in those with dementia compared to those without dementia (t = 4.4608, p = 0.0002) but did not differ between amnestic MCI and control (t = 1.6116, p = 0.1130). Across all participants, plasma NfL did not predict DMN FC (Β = 0.0045, p = 0.4830). However, higher plasma NfL was marginally associated with higher DMN FC in those with dementia (Β = 0.0045, p = 0.0657) but not in those without dementia (Β = 0.0021, p = 0.3160). Moreover, in those without dementia, higher plasma NfL predicted higher DMN FC in APOE ε4 carriers (Β = 0.0079, p = 0.0312) but not in APOE ε4 noncarriers (Β = 0.0023, p = 0.4871).ConclusionOur results indicate that the increase of DMN FC, seen at early stages of AD (Damoiseaux et al., 2012), is significantly associated with more neuronal damage in APOE ε4 carriers without dementia.

Plasma NfL predicts default mode network functional connectivity in older adults at higher risk for Alzheimer’s disease

AbstractBackgroundNeurofilament light (NfL) is a measure of neuronal damage and has the potential as a monitoring and prognostic biomarker of Alzheimer’s disease (AD) (Mattsson et al., 2019). Likewise, alterations in default mode network (DMN) functional connectivity (FC) may predict AD progression (Jones et al., 2016). Here, we investigated the relationship between plasma NfL levels and DMN FC along the continuum of AD, and explored whether APOE ε4 status influenced this relationship.MethodResting‐state functional MRI data and blood samples were available for 103 older adults (17 with AD dementia, age: 69.2±6.9; m/f: 8/9; CDR: 0.7±0.3; and 86 without dementia (includes amnestic MCI and control), age: 71.7±7.4; m/f: 21/65; CDR: 0.3±0.2). Plasma NfL was measured using a single‐molecule array (Simoa) assay. We calculated DMN FC using 32 high consensus DMN ROIs from Dworetsky et al. (2021). DMN FC was defined as the average correlation between the mean time‐series of three ROIs labeled as posterior cingulate cortex and those of all the other ROIs. Participants’ APOE status was defined as APOE ε4 carriers (ε3/ε4 or ε4/ε4) and noncarriers (ε3/ε3). Multiple regression was run with DMN FC as the outcome variable, plasma NfL as the predictor, and age and sex as covariates.ResultPlasma NfL levels were higher in those with dementia compared to those without dementia (t = 4.4608, p = 0.0002) but did not differ between amnestic MCI and control (t = 1.6116, p = 0.1130). Across all participants, plasma NfL did not predict DMN FC (Β = 0.0045, p = 0.4830). However, higher plasma NfL was marginally associated with higher DMN FC in those with dementia (Β = 0.0045, p = 0.0657) but not in those without dementia (Β = 0.0021, p = 0.3160). Moreover, in those without dementia, higher plasma NfL predicted higher DMN FC in APOE ε4 carriers (Β = 0.0079, p = 0.0312) but not in APOE ε4 noncarriers (Β = 0.0023, p = 0.4871).ConclusionOur results indicate that the increase of DMN FC, seen at early stages of AD (Damoiseaux et al., 2012), is significantly associated with more neuronal damage in APOE ε4 carriers without dementia.

Musical Experience Relates to Insula-Based Functional Connectivity in Older Adults.

Engaging in musical activities throughout the lifespan may protect against age-related cognitive decline and modify structural and functional connectivity in the brain. Prior research suggests that musical experience modulates brain regions that integrate different modalities of sensory information, such as the insula. Most of this research has been performed in individuals classified as professional musicians; however, general musical experiences across the lifespan may also confer beneficial effects on brain health in older adults. The current study investigated whether general musical experience, characterized using the Goldsmith Music Sophistication Index (Gold-MSI), was associated with functional connectivity in older adults (age = 65.7 ± 4.4, n = 69). We tested whether Gold-MSI was associated with individual differences in the functional connectivity of three a priori hypothesis-defined seed regions in the insula (i.e., dorsal anterior, ventral anterior, and posterior insula). We found that older adults with more musical experience showed greater functional connectivity between the dorsal anterior insula and the precentral and postcentral gyrus, and between the ventral anterior insula and diverse brain regions, including the insula and prefrontal cortex, and decreased functional connectivity between the ventral anterior insula and thalamus (voxel p < 0.01, cluster FWE p < 0.05). Follow-up correlation analyses showed that the singing ability subscale score was key in driving the association between functional connectivity differences and musical experience. Overall, our findings suggest that musical experience, even among non-professional musicians, is related to functional brain reorganization in older adults.

Auditory attentional load attenuates age-related audiovisual integration: An EEG study

Studies have revealed that visual attentional load modulated audiovisual integration (AVI) greatly; however, auditory and visual attentional resources are separate to some degree, and task-irrelevant auditory information could arouse much faster and larger attentional alerting effects than visible information. Here, we aimed to explore how auditory attentional load influences AVI and how aging could have an effect. Thirty older and 30 younger adults participated in an AV discrimination task with an additional auditory distractor competing for attentional resources. The race model analysis revealed highest AVI in the low auditory attentional load condition (low > no > medium > high, pairwise comparison, all p ≤ 0.047) for younger adults and a higher AVI under the no auditory attentional-load condition (p = 0.008), but there was a lower AVI under the low (p = 0.019), medium (p < 0.001), and high (p = 0.021) auditory attentional-load conditions for older adults than for younger adults. The time-frequency analysis revealed higher theta- and alpha-band AVI oscillation under no and low auditory attentional-load conditions than under medium and high auditory attentional-load conditions for both older (all p ≤ 0.011) and younger (all p ≤ 0.024) adults. Additionally, Weighted Phase lag index (WPLI) analysis revealed higher theta-band and lower alpha-band global functional connectivity for older adults during AV stimuli processing (all p ≤ 0.031). These results suggested that the AVI was higher in the low attentional-load condition than in the no attentional-load condition but decreased inversely with increasing of attentional load and that there was a significant aging effect in older adults. In addition, the strengthened theta-band global functional connectivity in older adults during AV stimuli processing might be an adaptive phenomenon for age-related perceptual decline.

Physical activity moderates the association between executive function and functional connectivity in older adults.

Recent evidence suggests that physical activity may influence the functional connectivity of the aging brain. The purpose of this study was to examine the influence of physical activity on the association between executive function and functional connectivity of key brain networks and graph theory metrics in community-dwelling older adults. Participants were 47 older adults (M = 73 years; SD = 5.92) who participated in neuropsychological testing, physical activity measurements, and magnetic resonance imaging (MRI). Seed-to-voxel moderation analyses and graph theory analyses were conducted. Physical activity was significantly positively associated with default mode network functional connectivity (DMN FC; Posterior Cingulate Gyrus, p-FDR = 0.005; Frontal Pole (L), p-FDR = 0.005; Posterior Cingulate Gyrus, p-FDR = 0.006; Superior Frontal Gyrus (L), p-FDR = 0.016) and dorsal attention network functional connectivity (DAN FC; Inferior Frontal Gyrus Pars Opercularis (R), p-FDR = 0.044). The interaction between physical activity and executive function on the DMN FC and DAN FC was analyzed. The interaction between executive function and physical activity was significantly associated with DMN FC. When this significant interaction was probed, the association between physical activity and DMN FC differed between levels of high and low executive function such that the association was only significant at levels of high executive function. These results suggest that greater physical activity in later life is associated with greater DMN and DAN FC and provides evidence for the importance of physical activity in cognitively healthy older adults.

Musical experience relates to functional connectivity in older adults

Previous studies have shown that engaging in musical activities throughout the lifespan may buffer age-related decline in auditory and motor function, as well as in general cognitive function. MRI studies have demonstrated that individuals with musical training and experience exhibited greater grey matter volume and functional connectivity in extensive brain regions, especially in auditory and motor systems, compared to matched controls with no particular musical training or experience. Therefore, musical activity is a potential protective factor for brain health across lifespan. However, how lifespan musical experience shapes functional connectivity in older adults is still unknown. The current analysis investigated whether general musical experience (Goldsmith Music Sophistication Index) is associated with functional connectivity in older adults (age=65.7±4.4, n=69), focusing on seed regions in primary motor areas (bilateral precentral gyrus) and primary auditory regions (bilateral anterior/posterior superior temporal gyrus) and their functional connectivity towards other areas throughout the whole brain. We found that older adults with more musical experience showed greater functional connectivity between anterior superior temporal gyrus and insula (R2=0.10, p=0.01), and between posterior superior temporal gyrus and cerebellum (R2=0.08, p=0.02). However, musical experience and music-related functional connectivity was not significantly correlated with general cognitive functions in our sample. Overall, our findings suggest that older adults with more musical experience might be more efficient in some aspects of auditory processing and auditory-motor skills, but this may not transfer towards domain-general cognitive tests. Our results support the notion that even non-professional engagement in musical experiences may afford benefits to the aging brain.

Executive control network (ECN) and default mode network (DMN) functional connectivity in older adults with remitted depression, mild cognitive impairment, Alzheimer’s dementia, or normal cognition

AbstractBackgroundMajor Depressive Disorder (MDD) is associated with an increased risk of developing Alzheimer’s dementia (AD). The present study aims to understand risk for AD by comparing resting state functional connectivity (FC) in putatively shared vulnerability networks; executive control network (ECN) or default mode network (DMN) among older adults who are either healthy or have a history of MDD, MCI, or AD.MethodWe assessed brain functional alterations in ECN and DMN in five groups at‐risk for dementia: remitted MDD, non‐amnestic mild cognitive impairment (naMCI), MDD+naMCI, amnestic MCI (aMCI), and MDD+aMCI. The analysis also included individuals with AD and healthy controls (HC). Resting‐state functional MRI data were acquired on the same 3T scanner. Following quality control (n=330), dual regression was conducted. The ECN and DMN group‐ICA (independent component analysis) were selected from the Smith atlas. Next, the group difference in the functional connectivity (FC) of each network was calculated using PALM (Permutation Analysis of Linear Models).ResultFor within‐network FC in the ECN or DMN, we found no difference between participant groups. For between‐network FC, we found a significant difference between the DMN and the superior parietal lobe (SPL); post‐hoc tests showed decreased anti‐correlation between the AD group compared to the MDD and HC groups (p&lt;0.05).ConclusionThe between‐network difference in DMN among groups was driven by the AD group. There was minimal distinction among those with remitted MDD or MCI. It is possible that remitted MDD may not act as mechanistic risk for AD in ECN or DMN networks.

Multifocal Transcranial Direct Current Stimulation Modulates Resting-State Functional Connectivity in Older Adults Depending on the Induced Current Density.

Combining non-invasive brain stimulation (NIBS) with resting-state functional magnetic resonance imaging (rs-fMRI) is a promising approach to characterize and potentially optimize the brain networks subtending cognition that changes as a function of age. However, whether multifocal NIBS approaches are able to modulate rs-fMRI brain dynamics in aged populations, and if these NIBS-induced changes are consistent with the simulated electric current distribution on the brain remains largely unknown. In the present investigation, thirty-one cognitively healthy older adults underwent two different multifocal real transcranial direct current stimulation (tDCS) conditions (C1 and C2) and a sham condition in a crossover design during a rs-fMRI acquisition. The real tDCS conditions were designed to electrically induce two distinct complex neural patterns, either targeting generalized frontoparietal cortical overactivity (C1) or a detachment between the frontal areas and the posteromedial cortex (C2). Data revealed that the two tDCS conditions modulated rs-fMRI differently. C1 increased the coactivation of multiple functional couplings as compared to sham, while a smaller number of connections increased in C1 as compared to C2. At the group level, C1-induced changes were topographically consistent with the calculated electric current density distribution. At the individual level, the extent of tDCS-induced rs-fMRI modulation in C1 was related with the magnitude of the simulated electric current density estimates. These results highlight that multifocal tDCS procedures can effectively change rs-fMRI neural functioning in advancing age, being the induced modulation consistent with the spatial distribution of the simulated electric current on the brain. Moreover, our data supports that individually tailoring NIBS-based interventions grounded on subject-specific structural data might be crucial to increase tDCS potential in future studies amongst older adults.

EEG-Based Resting-State Functional Connectivity in Older Adults and Its Link to Motor Performance

Turning is a component of gait that requires planning for movement of multiple body segments and the sophisticated integration of sensory information from the vestibular, visual, and somatosensory systems. These aspects of turning have led to growing interest to quantify turning in clinical populations to characterize deficits or identify disease progression. However, turning may be affected by environmental differences, and the degree to which turning assessments are comparable across research or clinical sites has not yet been evaluated.The aim of this study was to determine the extent to which peak turning speeds are equivalent between two sites for a variety of mobility tasks.Data were collected at two different sites using separate healthy young adult participants (n = 47 participants total), but recruited using identical inclusion and exclusion criteria. Participants at each site completed three turning tasks: a one-minute walk (1 MW) along a six-meter walkway, a modified Illinois Agility Test (mIAT), and a custom clinical turning course (CCTC). Peak yaw turning speeds were extracted from wearable inertial sensors on the head, trunk, and pelvis. Between-site differences and two one-sided tests (TOST) were used to determine equivalence between sites, based on a minimum effect size reported between individuals with mild traumatic brain injury and healthy control subjects.No outcomes were different between sites, and equivalence was determined for 6/21 of the outcomes. These findings suggest that some turning tasks and outcome measures may be better suited for multi-site studies. The equivalence results are also dependent on the minimum effect size of interest; nearly all outcomes were equivalent across sites when larger minimum effect sizes of interest were used.Together, these results suggest some tasks and outcome measures may be better suited for multi-site studies and literature-based comparisons.

Executive Control Network (ECN) and Default Mode Network (DMN) Functional Connectivity in Older Adults With Remitted Depression, Mild Cognitive Impairment, Alzheimer’s Dementia, or Normal Cognition

Executive Control Network (ECN) and Default Mode Network (DMN) Functional Connectivity in Older Adults With Remitted Depression, Mild Cognitive Impairment, Alzheimer’s Dementia, or Normal Cognition

Improvements in memory and brain functional connectivity in older adults with subjective cognitive complaints following multiple‐modality exercise and mind‐motor training: An exploratory sub‐study

AbstractBackgroundWhether task‐based brain functional connectivity (FC) following exercise suggests adaptations in preferential brain regions is unclear. The objective of this study was to explore cognitive function and FC changes following multiple‐modality exercise and mind‐motor training in older adults with subjective cognitive complaints.MethodsWe included older adults (n=127, mean age 67.5 [7.3] years, 71% women) randomized to 45 minutes of multiple‐modality exercise with 15 minutes of mind‐motor training (M4 group, n = 63) or an active control group (M2 group, n = 64). Both groups exercised 60 minutes/day, 3 days/week, for 24 weeks. Participants completed twelve cognitive tasks from the Cambridge Brain Sciences (CBS) battery at baseline and follow‐up (memory, reasoning, concentration and planning tasks). A subsample of participants from the M4 group (n = 9, mean age 67.8 [8.8] years, 8 women) also underwent 5 minutes of continuous fMRI data collection while completing four CBS memory tasks. Behavioural data were analyzed using linear mixed models for repeated measures, and paired samples t‐test. All fMRI data were analyzed using group‐level independent component denoising and dual regression procedures, correcting for voxel‐wise comparisons.ResultsThe M4 group showed greater improvements in the Paired Associates tasks compared to the M2 group at 24 weeks (mean difference: 0.47, 95% confidence interval: .08 to .86, p = 0.019). No other results were found to be significant. For our fMRI analysis, dual regression revealed significant decreased FC co‐activation in the right precentral/postcentral gyri after the exercise program during the Spatial Span task (corrected p = 0.008) with no change in the behavioural task performance. Only trends for changes in FC were found for the other tasks (all corrected p &lt; 0.09). For the Paired Associates task, there was a trend for increased co‐activation in the right temporal lobe (Brodmann Area = 38, corrected p = 0.07), and left middle frontal temporal gyrus (corrected p = 0.06).ConclusionsOur findings provide insight into the potential of our multiple‐modality exercise and mind‐motor training intervention to promote improvements in behavioural measures of visuospatial memory, as well as, impart FC adaptations in brain regions relevant to Alzheimer’s disease risk.

Characteristics of resting-state functional connectivity in older adults after the PICMOR intervention program: a preliminary report

BackgroundThe present study aimed to provide a basis for future research examining the neural mechanisms that underlie the beneficial effect of an intervention program, Photo-Integrated Conversation Moderated by Robots (PICMOR), on verbal fluency in older adults as identified in our previous randomized controlled trial. In this preliminary report, we conducted an additional experiment using resting-state functional magnetic resonance imaging (rsfMRI) after the intervention period. Specifically, we investigated the resting-state functional connectivity (rsFC) characteristics of the intervention group (INT) compared to the control group (CONT).MethodsrsfMRI data were acquired from 31 and 30 participants in INT and CONT, respectively, after the intervention. In the analyses, two of the most important regions in verbal fluency, the left inferior and middle frontal gyri, were selected as seed regions, and the rsFCs were compared between groups. We also conducted regression analyses for rsFCs using the difference in individual phonemic verbal fluency task (PVFT) scores between the pre- and post-intervention periods (i.e., post- minus pre-intervention) as an independent variable.ResultsWe found higher rsFC in INT than in CONT between the left inferior frontal gyrus as a seed region and the temporal pole and middle frontal gyrus. The rsFC strength between the left inferior frontal gyrus and temporal pole positively correlated with an increased PVFT score between the pre- and post-intervention periods. In contrast, we found lower rsFC in INT than in CONT between the left middle frontal gyrus as a seed region and the posterior cingulate cortex, precuneus, and postcentral gyrus.ConclusionsOur findings suggest that the beneficial intervention effect of PICMOR on verbal fluency is characterized by enhanced rsFC of the left inferior frontal gyrus with semantic and executive control-related regions and suppressed rsFC between the left middle frontal gyrus and posterior cortical midline structures. No definitive conclusions can be made because of a lack of rsfMRI data before the intervention. However, this pilot study provides the candidates for rsFCs, reflecting the beneficial effects of PICMOR on the brain network involved in verbal fluency.Trial registrationThe trial was retrospectively registered at the UMIN Clinical Trials Registry (UMIN000036667) (May 7th, 2019).

Self-reported experiences of discrimination in older black adults are associated with insula functional connectivity.

Self-reported experiences of discrimination are associated with a number of negative health outcomes. However, the neurobiological correlates of discrimination remain elusive. Recent neuroimaging work suggests that the amygdala is sensitive to forms of social adversity and the insula is involved in assessments of trust. We hypothesized that functional connectivity (FC) of these brain regions may be associated with discrimination in older Black adults. One-hundred and twenty-four nondemented older Black adults participating in the Minority Aging Research Study or the Clinical Core study of the Rush Alzheimer's Disease Center completed a measure of self-reported experiences of discrimination and a 3T MRI brain scan including structural T1 and resting-state fMRI EPIBOLD sequences. The right and left amygdala and insula regions were anatomically delineated as ROIs according to the Harvard-Oxford Brain Atlas and whole-brain voxelwise FC analyses were conducted using default parameters in the CONN toolbox. In regression analyses controlling for demographics and global cognition, self-reported experiences of discrimination were associated with greater FC between the left insula and the bilateral intracalcarine cortex, weaker FC between the left insula and the left dorsolateral prefrontal cortex, and weaker FC between the right insula and the left supplementary motor area. Amygdala analyses yielded no significant findings. Greater self-reported experiences of discrimination are associated with differential insula functional connectivity in older adults. More specifically, results suggest that discrimination is associated with differential connectivity of a key region (the insula) involved in trust perception.

Neural correlates of working memory training: Evidence for plasticity in older adults

Brain activity typically increases with increasing working memory (WM) load, regardless of age, before reaching an apparent ceiling. However, older adults exhibit greater brain activity and reach ceiling at lower loads than younger adults, possibly reflecting compensation at lower loads and dysfunction at higher loads. We hypothesized that WM training would bolster neural efficiency, such that the activation peak would shift towards higher memory loads after training. Pre-training, older adults showed greater recruitment of the WM network than younger adults across all loads, with decline at the highest load. Ten days of adaptive training on a verbal WM task improved performance and led to greater brain responsiveness at higher loads for both groups. For older adults the activation peak shifted rightward towards higher loads. Finally, training increased task-related functional connectivity in older adults, both within the WM network and between this task-positive network and the task-negative/default-mode network. These results provide new evidence for functional plasticity with training in older adults and identify a potential signature of improvement at the neural level.