Changes In Brain Connectivity Research Articles

Brain Scans May Offer Clues About Depression Remission

Brain Scans May Offer Clues About Depression Remission

Reorganization of Brain Networks as a Substrate of Resilience: An Analysis of Cytochrome c Oxidase Activity in Rats.

The unpredictable chronic mild stress (UCMS) model has been used to induce depressive-like symptoms in animal models, showing adequate predictive validity. Our work aims to evaluate the effects of environmental enrichment (EE) on resilience in this experimental model of depression. We also aim to assess changes in brain connectivity using cytochrome c oxidase histochemistry in cerebral regions related to cognitive-affective processes associated with depressive disorder: dorsal hippocampus, prefrontal cortex, amygdala, accumbens, and habenula nuclei. Five groups of rats were used: UCMS, EE, EE+UCMS (enrichment+stress), BG (basal level of brain activity), and CONT (behavioral tests only). We assessed the hedonic responses elicited by sucrose solution using a consumption test; the anxiety level was evaluated using the elevated zero maze test, and the unconditioned fear responses were assessed by the cat odor test. The behavioral results showed that the UCMS protocol induces elevated anhedonia and anxiety. But these responses are attenuated previous exposure to EE. Regarding brain activity, the UCMS group showed greater activity in the habenula compared to the EE+UCMS group. EE induced a functional reorganization of brain activity. The EE+UCMS and UCMS groups showed different patterns of connections between brain regions. Our results showed that EE favors greater resilience and could reduce vulnerability to disorders such as depression and anxiety, modifying metabolic brain activity.

Antidepressant treatment-related brain activity changes in remitted major depressive disorder.

Recent evidence has shown that some brain regions are core hubs and play a key role in the treatment of depression. Twenty-five unmedicated patients with major depressive disorder (MDD) were included, and telephone follow-up was performed at 8, 24, and 48 weeks after enrollment. After reaching clinical remission, they were scheduled for a second magnetic resonance imaging scan and clinical evaluation. Thirty-one healthy controls were also investigated. The intrinsic functional connectivity (degree centrality) of each participant was mapped using a computationally efficient approach. Then, functional connectivity of patients was calculated between the identified regions of interest by degree centrality analysis and every voxel. Later, linear regression analysis was used to identify potential variables predictive of an improvement in disease severity. The prominent hubs identified by degree centrality analysis included the cerebellum, inferior temporal gyrus, lingual gyrus, dorsal medial prefrontal cortex (DMPFC), and dorsal lateral prefrontal cortex. We also found that the increased degree centrality of DMPFC was associated with improvement in depressive symptoms. The brain activity associated with antidepressant effects, especially brain connectivity changes in the left DMPFC, can potentially be used to monitor treatment response and predict treatment outcomes.

Functional and structural brain network development in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a prevalent childhood neurodevelopmental disorder. Given the profound brain changes that occur during childhood and adolescence, it is important to examine longitudinal changes of both functional and structural brain connectivity across development in ADHD. This study aimed to examine the development of functional and structural connectivity in children with ADHD compared to controls using graph metrics. One hundred and seventy five individuals (91 children with ADHD and 84 non-ADHD controls) participated in a longitudinal neuroimaging study with up to three waves. Graph metrics were derived from 370 resting state fMRI (197 Control, 173 ADHD) and 297 diffusion weighted imaging data (152 Control, 145 ADHD) acquired between the ages of 9 and 14. For functional connectivity, children with ADHD (compared to typically developing children) showed lower degree, local efficiency and betweenness centrality predominantly in parietal, temporal and visual cortices and higher degree, local efficiency and betweenness centrality in frontal, parietal, and temporal cortices. For structural connectivity, children with ADHD had lower local efficiency in parietal and temporal cortices and, higher degree and betweenness centrality in frontal, parietal and temporal cortices. Further, differential developmental trajectories of functional and structural connectivity for graph measures were observed in higher-order cognitive and sensory regions. Our findings show that topology of functional and structural connectomes matures differently between typically developing controls and children with ADHD during childhood and adolescence. Specifically, functional and structural neural circuits associated with sensory and various higher order cognitive functions are altered in children with ADHD.

The instant effect of embodiment via mirror visual feedback on electroencephalogram-based brain connectivity changes: A pilot study.

The therapeutic efficacy of mirror visual feedback (MVF) is attributed to the perception of embodiment. This study intends to investigate the instantaneous effect of embodiment on brain connectivity. Twelve healthy subjects were required to clench and open their non-dominant hands and keep the dominant hands still during two experimental sessions. In the first session, the dominant hand was covered and no MVF was applied, named the sham-MVF condition. Random vibrotactile stimulations were applied to the non-dominant hand with MVF in the subsequent session. Subjects were asked to pedal while having embodiment perception during motor tasks. As suggested by previous findings, trials of no vibration and continuous vibration were selected for this study, named the condition of MVF and vt-MVF. EEG signals were recorded and the alterations in brain connectivity were analyzed. The average node degrees of sham-MVF, MVF, and vt-MVF conditions were largely different in the alpha band (9.94, 11.19, and 17.37, respectively). Further analyses showed the MVF and vt-MVF had more nodes with a significantly large degree, which mainly occurred in the central and the visual stream involved regions. Results of network metrics showed a significant increment of local and global efficiency, and a reduction of characteristic path length for the vt-MVF condition in the alpha and beta bands compared to sham-MVF, and in the alpha band compared to MVF. Similar trends were found for MVF condition in the beta band compared to sham-MVF. Moreover, significant leftward asymmetry of global efficiency and rightward asymmetry of characteristic path length was reported in the vt-MVF condition in the beta band. These results indicated a positive impact of embodiment on network connectivity and neural communication efficiency, which reflected the potential mechanisms of MVF for new insight into neural modulation.

Tensorial independent component analysis reveals social and reward networks associated with major depressive disorder.

Major depressive disorder (MDD) has been associated with changes in functional brain connectivity. Yet, typical analyses of functional connectivity, such as spatial independent components analysis (ICA) for resting-state data, often ignore sources of between-subject variability, which may be crucial for identifying functional connectivity patterns associated with MDD. Typically, methods like spatial ICA will identify a single component to represent a network like the default mode network (DMN), even if groups within the data show differential DMN coactivation. To address this gap, this project applies a tensorial extension of ICA (tensorial ICA)-which explicitly incorporates between-subject variability-to identify functionally connected networks using functional MRI data from the Human Connectome Project (HCP). Data from the HCP included individuals with a diagnosis of MDD, a family history of MDD, and healthy controls performing a gambling and social cognition task. Based on evidence associating MDD with blunted neural activation to rewards and social stimuli, we predicted that tensorial ICA would identify networks associated with reduced spatiotemporal coherence and blunted social and reward-based network activity in MDD. Across both tasks, tensorial ICA identified three networks showing decreased coherence in MDD. All three networks included ventromedial prefrontal cortex, striatum, and cerebellum and showed different activation across the conditions of their respective tasks. However, MDD was only associated with differences in task-based activation in one network from the social task. Additionally, these results suggest that tensorial ICA could be a valuable tool for understanding clinical differences in relation to network activation and connectivity.

Repurposing the mucolytic agent ambroxol for treatment of sub-acute and chronic ischaemic stroke.

Ambroxol is a well-known mucolytic expectorant, which has gained much attention in amyotrophic lateral sclerosis, Parkinson's and Gaucher's disease. A specific focus has been placed on ambroxol's glucocerebrosidase-stimulating activity, on grounds that the point mutation of the gba1 gene, which codes for this enzyme, is a risk factor for developing Parkinson's disease. However, ambroxol has been attributed other characteristics, such as the potent inhibition of sodium channels, modification of calcium homeostasis, anti-inflammatory effects and modifications of oxygen radical scavengers. We hypothesized that ambroxol could have a direct impact on neuronal rescue if administered directly after ischaemic stroke induction. We longitudinally evaluated 53 rats using magnetic resonance imaging to examine stroke volume, oedema, white matter integrity, resting state functional MRI and behaviour for 1 month after ischemic stroke onset. For closer mechanistic insights, we evaluated tissue metabolomics of different brain regions in a subgroup of animals using ex vivo nuclear magnetic resonance spectroscopy. Ambroxol-treated animals presented reduced stroke volumes, reduced cytotoxic oedema, reduced white matter degeneration, reduced necrosis, improved behavioural outcomes and complex changes in functional brain connectivity. Nuclear magnetic resonance spectroscopy tissue metabolomic data at 24 h post-stroke proposes several metabolites that are capable of minimizing post-ischaemic damage and that presented prominent shifts during ambroxol treatment in comparison to controls. Taking everything together, we propose that ambroxol catalyzes recovery in energy metabolism, cellular homeostasis, membrane repair mechanisms and redox balance. One week of ambroxol administration following stroke onset reduced ischaemic stroke severity and improved functional outcome in the subacute phase followed by reduced necrosis in the chronic stroke phase.

Influence of vigilance-related arousal on brain dynamics: Potentials of new approaches

Growing research has focused on how mesoscopic activity in the brain develops over time and space. Recent influential studies using functional imaging have characterized brain dynamics in terms of the spread of activation across the brain following a unimodal to transmodal axis. In parallel, a number of studies have assessed changes of brain connectivity in terms of vigilance-linked arousal. Here I offer a view on how these two lines of research can lead to a deeper understanding of how arousal shapes the brain's dynamic behavior. This knowledge could have great impact on the investigation of mental disease.

Unblinding and demand characteristics in the treatment of depression

Blinding of treatment allocation in clinical trials in psychiatry is regarded as an ideal. The potential impact of unblinding chimes with a general concern for psychological research: so-called demand characteristics can undermine confidence in findings from experimental and clinical studies. Scepticism can result in nihilism. The reliance on subjective report of symptoms in clinical trials of drug efficacy in depression provides an important example. It is regularly implied that if subjective effects, including specific adverse reactions, unblind participants to an active treatment then evidence for its efficacy is suspect. In fact, the strong association between dose and subjective effects does not translate into a strong relationship with efficacy in randomised controlled trials (RCTs) of conventional antidepressant drugs; this observation falsifies the proposition that unblinding is the principal mechanism driving RCT outcomes in studies of depression. Instead, changes in brain function, that occur soon after treatment starts, do predict treatment outcomes and align with our understanding of neurotransmitter effects from neuroscience. Psychedelic experience for the treatment of depression must be unblinding, but the effect results directly from serotonergic receptor activation and changes in brain connectivity. Where such effects are part of a novel mechanism of action, a strong dose response relationship would be expected, irrespective of unblinding. We highlight the importance of exploring blinding as a mechanism, confirming dose-related outcomes, and dissociating unblinding effects from efficacy. Unblinding does not necessarily invalidate the subjective experience of sustained recovery from depression.

Persistent Brain Connectivity Changes in Healthy Volunteers Following Nitrous Oxide Inhalation

BackgroundNitrous oxide holds promise in the treatment of major depressive disorder. Its psychotropic effects and NMDA receptor antagonism have led to comparisons with ketamine. Despite longstanding use, persistent effects of nitrous oxide on the brain have not been characterized. MethodsSixteen healthy volunteers were recruited in a double-blind crossover study. In randomized order, individuals underwent a 1-hour inhalation of either 50% nitrous oxide/oxygen or air/oxygen mixtures. At least two 7.5-minute echo-planar resting-state functional magnetic resonance imaging scans were obtained before and at 2 and 24 hours after each inhalation (average 130 min/participant). Using the time series of preprocessed, motion artifact–scrubbed, and nuisance covariate–regressed imaging data, interregional signal correlations were measured and converted to T scores. Hierarchical clustering and linear mixed-effects models were employed. ResultsNitrous oxide inhalation produced changes in global brain connectivity that persisted in the occipital cortex at 2 and 24 hours postinhalation (p < .05, false discovery rate–corrected). Analysis of resting-state networks demonstrated robust strengthening of connectivity between regions of the visual network and those of the dorsal attention network, across 2 and 24 hours after inhalation (p < .05, false discovery rate–corrected). Weaker changes in connectivity were found between the visual cortex and regions of the frontoparietal and default mode networks. Parallel analyses following air/oxygen inhalation yielded no significant changes in functional connectivity. ConclusionsNitrous oxide inhalation in healthy volunteers revealed persistent increases in global connectivity between regions of primary visual cortex and dorsal attention network. These findings suggest that nitrous oxide inhalation induces neurophysiological cortical changes that persist for at least 24 hours.

Age Related Functional Connectivity Signature Extraction Using Energy-Based Machine Learning Techniques.

The study of brain connectivity plays an important role in understanding the functional organizations of the brain. It also helps to identify connectivity signatures that can be used for evaluating neural disorders and monitoring treatment efficacy. In this work, age-related changes in brain connectivity are studied to obtain aging signatures based on various modeling techniques. These include an energy-based machine learning technique to identify brain network interaction differences between two age groups with a large (30 years) age gap between them. Disconnectivity graphs and activation maps of the seven prominent resting-state networks (RSN) were obtained from functional MRI data of old and young adult subjects. Two-sample t-tests were performed on the local minimums with Bonferroni correction to control the family-wise error rate. These local minimums are connectivity states showing not only which brain regions but also how strong they are working together. They work as aging signatures that can be used to differentiate young and old groups. We found that the attention network's connectivity signature is a state with all the regions working together and young subjects have a stronger average connectivity among these regions. We have also found a common pattern between young and old subjects where the left and right brain regions of the frontal network are sometimes working separately instead of together. In summary, in this work, we combined machine learning and statistical approaches to extract connectivity signatures, which can be utilized to distinguish aging brains and monitor possible treatment efficacy.

Effects of inhaled cannabis high in Δ9-THC or CBD on the aging brain: A translational MRI and behavioral study.

With the recent legalization of inhaled cannabis for medicinal and recreational use, the elderly represents one of the newest, rapidly growing cohorts of cannabis users. To understand the neurobiological effects of cannabis on the aging brain, 19-20 months old mice were divided into three groups exposed to vaporized cannabis containing ~10% Δ9-THC, ~10% CBD, or placebo for 30 min each day. Voxel based morphometry, diffusion weighted imaging, and resting state functional connectivity data were gathered after 28 days of exposure and following a two-week washout period. Tail-flick, open field, and novel object preference tests were conducted to explore analgesic, anxiolytic, and cognitive effects of cannabis, respectively. Vaporized cannabis high in Δ9-THC and CBD achieved blood levels reported in human users. Mice showed antinociceptive effects to chronic Δ9-THC without tolerance while the anxiolytic and cognitive effects of Δ9-THC waned with treatment. CBD had no effect on any of the behavioral measures. Voxel based morphometry showed a decrease in midbrain dopaminergic volume to chronic Δ9-THC followed but an increase after a two-week washout. Fractional anisotropy values were reduced in the same area by chronic Δ9-THC, suggesting a reduction in gray matter volume. Cannabis high in CBD but not THC increased network strength and efficiency, an effect that persisted after washout. These data would indicate chronic use of inhaled cannabis high in Δ9-THC can be an effective analgesic but not for treatment of anxiety or cognitive decline. The dopaminergic midbrain system was sensitive to chronic Δ9-THC but not CBD showing robust plasticity in volume and water diffusivity prior to and following drug cessation an effect possibly related to the abuse liability of Δ9-THC. Chronic inhaled CBD resulted in enhanced global network connectivity that persisted after drug cessation. The behavioral consequences of this sustained change in brain connectivity remain to be determined.

Irritability in early to middle childhood: Cross-sectional and longitudinal associations with resting state amygdala and ventral striatum connectivity

BackgroundIrritability is a common symptom that may affect children’s brain development. This study aims to (1) characterize age-dependent and age-independent neural correlates of irritability in a sample of 4–8 year old children, and (2) examine early irritability as a predictor of change in brain connectivity over time. MethodsTypically developing children, ages 4–8 years, with varying levels of irritability were included. Resting state fMRI and parent-rated irritability (via Child Behavior Checklist; CBCL) were collected at up to three time points, resulting in a cross-sectional sample at baseline (N = 176, M = 6.27, SD = 1.49), and two subsamples consisting of children who were either 4 or 6 years old at baseline that were followed longitudinally for two additional timepoints, one- and two-years post-baseline. That is, a “younger” cohort (age 4 at baseline, n = 34, M age = 4.44, SD = 0.25) and an “older” cohort (age 6 at baseline, n = 29, M age = 6.50, SD = 0.30). Across our exploratory analyses, we examined how irritability related to seed-based intrinsic connectivity via whole-brain connectivity ANCOVAs using the left and right amygdala, and left and right ventral striatum as seed regions. ResultsCross-sectionally, higher levels of irritability were associated with greater amygdala connectivity with the posterior cingulate, controlling for child age. No age-dependent effects were observed in the cross-sectional analyses. Longitudinal analyses in the younger cohort revealed that early higher vs. lower levels of irritability, controlling for later irritability, were associated with decreases in amygdala and ventral striatum connectivity with multiple frontal and parietal regions over time. There were no significant findings in the older cohort. ConclusionsFindings suggest that irritability is related to altered neural connectivity during rest regardless of age in early to middle childhood and that early childhood irritability may be linked to altered changes in neural connectivity over time. Understanding how childhood irritability interacts with neural processes can inform pathophysiological models of pediatric irritability and the development of targeted mechanistic interventions.

Longitudinal changes in global structural brain connectivity and cognitive performance in former hospitalized COVID-19 survivors: an exploratory study

BackgroundLong-term sequelae of COVID-19 can result in reduced functionality of the central nervous system and substandard quality of life. Gaining insight into the recovery trajectory of admitted COVID-19 patients on their cognitive performance and global structural brain connectivity may allow a better understanding of the diseases' relevance.ObjectivesTo assess whole-brain structural connectivity in former non-intensive-care unit (ICU)- and ICU-admitted COVID-19 survivors over 2 months following hospital discharge and correlate structural connectivity measures to cognitive performance.MethodsParticipants underwent Magnetic Resonance Imaging brain scans and a cognitive test battery after hospital discharge to evaluate structural connectivity and cognitive performance. Multilevel models were constructed for each graph measure and cognitive test, assessing the groups' influence, time since discharge, and interactions. Linear regression models estimated whether the graph measurements affected cognitive measures and whether they differed between ICU and non-ICU patients.ResultsSix former ICU and six non-ICU patients completed the study. Across the various graph measures, the characteristic path length decreased over time (β = 0.97, p = 0.006). We detected no group-level effects (β = 1.07, p = 0.442) nor interaction effects (β = 1.02, p = 0.220). Cognitive performance improved for both non-ICU and ICU COVID-19 survivors on four out of seven cognitive tests 2 months later (p < 0.05).ConclusionAdverse effects of COVID-19 on brain functioning and structure abate over time. These results should be supported by future research including larger sample sizes, matched control groups of healthy non-infected individuals, and more extended follow-up periods.

Shared and Unique Changes in Brain Connectivity Among Depressed Patients After Remission With Pharmacotherapy Versus Psychotherapy.

The authors sought to determine the shared and unique changes in brain resting-state functional connectivity (rsFC) between patients with major depressive disorder who achieved remission with cognitive-behavioral therapy (CBT) or with antidepressant medication. The Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) trial randomized adults with treatment-naive major depressive disorder to 12 weeks of treatment with CBT (16 1-hour sessions) or medication (duloxetine 30-60 mg/day or escitalopram 10-20 mg/day). Resting-state functional MRI scans were performed at baseline and at week 12. The primary outcome was change in the whole-brain rsFC of four seeded brain networks among participants who achieved remission. Of the 131 completers with usable MRI data (74 female; mean age, 39.8 years), remission was achieved by 19 of 40 CBT-treated and 45 of 91 medication-treated patients. Three patterns of connectivity changes were observed. First, those who remitted with either treatment shared a pattern of reduction in rsFC between the subcallosal cingulate cortex and the motor cortex. Second, reciprocal rsFC changes were observed across multiple networks, primarily increases in CBT remitters and decreases in medication remitters. And third, in CBT remitters only, rsFC increased within the executive control network and between the executive control network and parietal attention regions. Remission from major depression via treatment with CBT or medication is associated with changes in rsFC that are mostly specific to the treatment modality, providing biological support for the clinical practice of switching between or combining these treatment approaches. Medication is associated with broadly inhibitory effects. In CBT remitters, the increase in rsFC strength between networks involved in cognitive control and attention provides biological support for the theorized mechanism of CBT. Reducing affective network connectivity with motor systems is a shared process important for remission with both CBT and medication.

Probing fMRI brain connectivity and activity changes during emotion regulation by EEG neurofeedback.

Despite the existence of several emotion regulation studies using neurofeedback, interactions among a small number of regions were evaluated, and therefore, further investigation is needed to understand the interactions of the brain regions involved in emotion regulation. We implemented electroencephalography (EEG) neurofeedback with simultaneous functional magnetic resonance imaging (fMRI) using a modified happiness-inducing task through autobiographical memories to upregulate positive emotion. Then, an explorative analysis of whole brain regions was done to understand the effect of neurofeedback on brain activity and the interaction of whole brain regions involved in emotion regulation. The participants in the control and experimental groups were asked to do emotion regulation while viewing positive images of autobiographical memories and getting sham or real (based on alpha asymmetry) EEG neurofeedback, respectively. The proposed multimodal approach quantified the effects of EEG neurofeedback in changing EEG alpha power, fMRI blood oxygenation level-dependent (BOLD) activity of prefrontal, occipital, parietal, and limbic regions (up to 1.9% increase), and functional connectivity in/between prefrontal, parietal, limbic system, and insula in the experimental group. New connectivity links were identified by comparing the brain functional connectivity between experimental conditions (Upregulation and View blocks) and also by comparing the brain connectivity of the experimental and control groups. Psychometric assessments confirmed significant changes in positive and negative mood states in the experimental group by neurofeedback. Based on the exploratory analysis of activity and connectivity among all brain regions involved in emotion regions, we found significant BOLD and functional connectivity increases due to EEG neurofeedback in the experimental group, but no learning effect was observed in the control group. The results reveal several new connections among brain regions as a result of EEG neurofeedback which can be justified according to emotion regulation models and the role of those regions in emotion regulation and recalling positive autobiographical memories.

The Effects of Whole-body Cold-water Immersion on Brain Connectivity Related to the Affective State in Adults Using fMRI: A Protocol of a Pre-post Experimental Design.

An emerging body of behavioural studies indicates that regular swimming in cold water has positive effects on mental health and wellbeing, such as reducing fatigue, improving mood, and lessening depressive symptoms. Moreover, some studies reported immediate effects of cold-water immersion (CWI) on elevating mood and increasing a positive emotional state. However, the neural mechanisms underlying these effects remain largely unknown. The lack of studies using neuroimaging techniques to investigate how a whole-body CWI affects neural processes has partly resulted from the lack of a tested experimental protocol. Previous protocols administered tonic limb cooling (1-10 °C) while recording functional magnetic resonance (fMRI) signals. However, using very low water temperature constitutes points of contrast to painful experiences that are different from what we experience after a whole-body head-out CWI. In our protocol, healthy adults unhabituated to cold water were scanned twice: immediately before (pre-CWI) and after (post-CWI) immersion in cold water (water temperature 20 °C) for 5 min. We recorded cardiac and ventilatory responses to CWI and assessed self-reported changes in positive and negative affects. Our protocol showed reliable changes in brain connectivity after a short exposure to cold water, thus enabling its use as a tested experimental framework in future studies.

Age-Related Changes in Risky Decision Making and Associated Neural Circuitry in a Rat Model.

Altered decision making at advanced ages can have a significant impact on an individual's quality of life and the ability to maintain personal independence. Relative to young adults, older adults make less impulsive and less risky choices; although these changes in decision making could be considered beneficial, they can also lead to choices with potentially negative consequences (e.g., avoidance of medical procedures). Rodent models of decision making have been invaluable for dissecting cognitive and neurobiological mechanisms that contribute to age-related changes in decision making, but they have predominantly used costs related to timing or probability of reward delivery and have not considered other equally important costs, such as the risk of adverse consequences. The current study therefore used a rat model of decision making involving risk of explicit punishment to examine age-related changes in this form of choice behavior in male rats, and to identify potential cognitive and neurobiological mechanisms that contribute to these changes. Relative to young rats, aged rats displayed greater risk aversion, which was not attributable to reduced motivation for food, changes in shock sensitivity, or impaired cognitive flexibility. Functional MRI analyses revealed that, overall, functional connectivity was greater in aged rats compared with young rats, particularly among brain regions implicated in risky decision making such as basolateral amygdala, orbitofrontal cortex, and ventral tegmental area. Collectively, these findings are consistent with greater risk aversion found in older humans, and reveal age-related changes in brain connectivity.

Sex differences in default mode network connectivity in healthy aging adults.

Women show an increased lifetime risk of Alzheimer's disease (AD) compared with men. Characteristic brain connectivity changes, particularly within the default mode network (DMN), have been associated with both symptomatic and preclinical AD, but the impact of sex on DMN function throughout aging is poorly understood. We investigated sex differences in DMN connectivity over the lifespan in 595 cognitively healthy participants from the Human Connectome Project-Aging cohort. We used the intrinsic connectivity distribution (a robust voxel-based metric of functional connectivity) and a seed connectivity approach to determine sex differences within the DMN and between the DMN and whole brain. Compared with men, women demonstrated higher connectivity with age in posterior DMN nodes and lower connectivity in the medial prefrontal cortex. Differences were most prominent in the decades surrounding menopause. Seed-based analysis revealed higher connectivity in women from the posterior cingulate to angular gyrus, which correlated with neuropsychological measures of declarative memory, and hippocampus. Taken together, we show significant sex differences in DMN subnetworks over the lifespan, including patterns in aging women that resemble changes previously seen in preclinical AD. These findings highlight the importance of considering sex in neuroimaging studies of aging and neurodegeneration.

NOVEL BEHAVIORAL INTERVENTIONS TARGETING COGNITIVE-MOTOR NEUROPLASTICITY IN OLDER ADULTS

Abstract Comparatively little is known about the ability of physical activity to improve or maintain cognitive function in older adults. Our Midwest Roybal Center uses social/behavioral theory to promote engagement in physical activity in order to improve this outcome. In 2019, we received funding to establish a Multimodal Connectomics Core that enabled investigators to examine concurrent changes in cognitive function and brain connectivity by providing access to fMRI imaging. The Connectomics Core enabled investigators for the first time to examine cognitive function and changes in brain connectivity simultaneously by providing access to fMRI imaging as well as MRI data storage and data analysis. It enabled measuring of standardized participant outcomes selected from the NIH toolbox. This Symposium describes findings from the first three completed pilots and discusses their implications for the field. The first pilot by Bronas examined effect of a 6-month home-based walking program in people chronic kidney disease on cognitive function and intervention induced neuroplasticity compared to usual care. The second pilot by Marquez adapted the Fit &amp; Strong! program to test the combined impact of physical activity and interactive health education for managing mood on cognitive function among older adults with depression. The third pilot by Bhatt examined the effectiveness of 4 weeks of exergaming combined explicit cognitive training on behavioral measures of fall-risk (physical and cognitive) and their associations with brain integrity measures. The discussant will initiate discussion based on outcomes of these pilots and future directions for developing them into larger studies or clinical translation.