Ashley R. Morgan

Using Network Science to Evaluate Exercise-Associated Brain Changes in Older Adults

Literature has shown that exercise is beneficial for cognitive function in older adults and that aerobic fitness is associated with increased hippocampal tissue and blood volumes. The current study used novel network science methods to shed light on the neurophysiological implications of exercise-induced changes in the hippocampus of older adults. Participants represented a volunteer subgroup of older adults that were part of either the exercise training (ET) or healthy aging educational control (HAC) treatment arms from the Seniors Health and Activity Research Program Pilot (SHARP-P) trial. Following the 4-month interventions, MRI measures of resting brain blood flow and connectivity were performed. The ET groups hippocampal cerebral blood flow (CBF) exhibited statistically significant increases compared to the HAC group. Novel whole-brain network connectivity analyses showed greater connectivity in the hippocampi of the ET participants compared to HAC. Furthermore, the hippocampus was consistently shown to be within the same network neighborhood (module) as the anterior cingulate cortex only within the ET group. Thus, within the ET group, the hippocampus and anterior cingulate were highly interconnected and localized to the same network neighborhood. This project shows the power of network science to investigate potential mechanisms for exercise-induced benefits to the brain in older adults. We show a link between neurological network features and CBF, and it is possible that this alteration of functional brain networks may lead to the known improvement in cognitive function among older adults following exercise.

Acute effect of a high nitrate diet on brain perfusion in older adults

AIMS Poor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults. METHODS AND RESULTS In this investigation we administered a high vs. low nitrate diet to older adults (74.7±6.9 years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex. CONCLUSION These results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning.

A cognitive training intervention improves modality-specific attention in a randomized controlled trial of healthy older adults

Age-related deficits in cognitive and sensory function can result in increased distraction from background sensory stimuli. This randomized controlled trial investigated the effects of a cognitive training intervention aimed at helping healthy older adults suppress irrelevant auditory and visual stimuli. Sixty-six participants received 8 weeks of either the modality-specific attention training program or an educational lecture control program. Participants who completed the intervention program had larger improvements in modality-specific selective attention following training than controls. These improvements also correlated with reductions in bimodal integration during selective attention. Further, the intervention group showed larger improvements than the control group in non-trained domains such as processing speed and dual-task completion, demonstrating the utility of modality-specific attention training for improving cognitive function in healthy older adults.

Reproducibility of Graph Metrics in fMRI Networks

The reliability of graph metrics calculated in network analysis is essential to the interpretation of complex network organization. These graph metrics are used to deduce the small-world properties in networks. In this study, we investigated the test-retest reliability of graph metrics from functional magnetic resonance imaging data collected for two runs in 45 healthy older adults. Graph metrics were calculated on data for both runs and compared using intraclass correlation coefficient (ICC) statistics and Bland–Altman (BA) plots. ICC scores describe the level of absolute agreement between two measurements and provide a measure of reproducibility. For mean graph metrics, ICC scores were high for clustering coefficient (ICC = 0.86), global efficiency (ICC = 0.83), path length (ICC = 0.79), and local efficiency (ICC = 0.75); the ICC score for degree was found to be low (ICC = 0.29). ICC scores were also used to generate reproducibility maps in brain space to test voxel-wise reproducibility for unsmoothed and smoothed data. Reproducibility was uniform across the brain for global efficiency and path length, but was only high in network hubs for clustering coefficient, local efficiency, and degree. BA plots were used to test the measurement repeatability of all graph metrics. All graph metrics fell within the limits for repeatability. Together, these results suggest that with exception of degree, mean graph metrics are reproducible and suitable for clinical studies. Further exploration is warranted to better understand reproducibility across the brain on a voxel-wise basis.

The Cooperative Lifestyle Intervention Program-II (CLIP-II): design and methods.

A complication of cardiovascular disease (CVD) and the metabolic syndrome (MetS) among older adults is loss of mobility. The American Heart Association has identified weight management as a core component of secondary prevention programs for CVD and is an important risk factor for physical disability. The American Society for Nutrition and the Obesity Society have highlighted the need for long-term randomized clinical trials to evaluate the independent and additive effects of diet-induced weight loss (WL) and physical activity in older persons on outcomes such as mobility, muscle function, and obesity related diseases. Here we describe the rationale, design, and methods of a translational study, the Cooperative Lifestyle Intervention Program-II (CLIP-II). CLIP-II will randomize 252 obese, older adults with CVD or MetS to a weight loss only treatment (WL), aerobic exercise training (AT)+WL, or resistance exercise training (RT)+WL for 18 months. The dual primary outcomes are mobility and knee extensor strength. The interventions will be delivered by YMCA community partners with our staff as trainers and advisers. This study will provide the first large scale trial to evaluate the effects of diet-induced WL on mobility in obese, older adults with CVD or MetS as compared to WL combined with two different modes of physical activity (AT and RT). Because uncertainty exists about the best approach for promoting WL in older adults due to concerns with the loss of lean mass, the design also permits a contrast between AT+WL and RT+WL on muscle strength.

Graph Theory Analysis of Functional Brain Networks and Mobility Disability in Older Adults

BACKGROUND The brains structural integrity is associated with mobility function in older adults. Changes in function may be evident earlier than changes in structure and may be more directly related to mobility. Therefore, we assessed whether functional brain networks varied with mobility function in older adults. METHODS Short Physical Performance Battery (SPPB) and resting state functional magnetic resonance imaging were collected on 24 young (mean age = 26.4±5.1) and 48 older (mean age = 72.04±5.1) participants. Older participants were divided into three groups by SPPB score: Low SPPB (score = 7-9), Mid SPPB (score = 10), High SPPB (score = 11-12).Graph theory-based methods were used to characterize and compare brain network organization. RESULTS Connectivity in the somatomotor cortex distinguished between groups based on SPPB score. The community structure of the somatomotor cortex was significantly less consistent in the Low SPPB group (mean = 0.097±0.05) compared with Young (mean = 0.163±0.09, p = .03) SPPB group. Striking differences were evident in second-order connections between somatomotor cortex and superior temporal gyrus and insula that reached statistical significance. The Low SPPB group (mean = 140.87±109.30) had a significantly higher number of connections than Young (mean = 45.05±33.79, p = .0003) or High (mean = 49.61±35.31, p = .002) SPPB group. CONCLUSIONS Older adults with poorer mobility function exhibited reduced consistency of somatomotor community structure and a greater number of secondary connections with vestibular and multisensory regions of the brain. Further study is needed to fully interpret these effects, but analysis of functional brain networks adds new insights to the contribution of the brain to mobility.

Drive for consumption, craving, and connectivity in the visual cortex during the imagery of desired food

There is considerable interest in understanding food cravings given the obesogenic environment of Western Society. In this paper we examine how the imagery of palatable foods affects cravings and functional connectivity in the visual cortex for people who differ on the power of food scale (PFS). Fourteen older, overweight/obese adults came to our laboratory on two different occasions. Both times they ate a controlled breakfast meal and then were restricted from eating for 2.5 h prior to scanning. On 1 day they consumed a BOOST® liquid meal after the period of food restriction, whereas on the other day they only consumed water (NO BOOST® condition). After these manipulations, they had an fMRI scan in which they were asked to image both neutral objects and their favorite snack foods; they also completed visual analog scales for craving, hunger, and the vividness of the imagery experiences. Irrespective of the BOOST® manipulation, we observed marked increases in food cravings when older, overweight/obese adults created images of favorite foods in their minds as opposed to creating an image of neutral objects; however, the increase in food craving following the imagery of desired food was more pronounced among those scoring high than low on the PFS. Furthermore, local efficiency within the visual cortex when imaging desired food was higher for those scoring high as compared to low on the PFS. The active imagery of desired foods seemed to have overpowered the BOOST® manipulation when evaluating connectivity in the visual cortex.

Graph-Theoretical Study of Functional Changes Associated with the Iowa Gambling Task

The primary aim of this study was to examine changes in functional brain network organization from rest to the Iowa Gambling Task (IGT) using a graph-theoretical approach. Although many functional neuroimaging studies have examined task-based activations in complex-decision making tasks, changes in functional network organization during this task remain unexplored. This study used a repeated-measures approach to examine changes in functional network organization across multiple sessions of resting-state and IGT scans. The results revealed that global network organization shifted from a local, clustered organization at rest to a more global, integrated organization during the IGT. In addition, network organization was stable across sessions of rest and the IGT. Regional analyses of the Default Mode Network (DMN) and Fronto-Parietal Network (FPN) revealed differential patterns of change in regional network organization from rest to the IGT. The results of this study reveal that global and regional network organization is significantly modulated across states and fairly stable over time, and that network changes in the FPN are particularly important in the decision-making processes necessary for successful IGT performance.

Functional Brain Network Changes Following Use of an Allostatic, Closed-Loop, Acoustic Stimulation Neurotechnology for Military-Related Traumatic Stress: Functional Brain Network Changes Following HIRREM in PTS

Post‐traumatic stress disorder is associated with connectivity changes in the default mode, central executive, and salience networks, and other brain regions. This study evaluated changes in network connectivity associated with usage of High‐resolution, relational, resonance‐based electroencephalic mirroring (HIRREM®; Brain State Technologies, Scottsdale, AZ), a closed‐loop, allostatic, acoustic stimulation neurotechnology, for military‐related traumatic stress.