Browsing by Author "Park, Denise C."
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Item ASL-MRICloud: An Online Tool for the Processing of ASL MRI Data(Wiley, 2018-12-26) Li, Yang; Liu, Peiying; Li, Yue; Fan, Hongli; Su, Pan; Peng, Shin-Lei; Park, Denise C.; Rodrigue, Karen M.; Jiang, Hangyi; Faria, Andreia V.; Ceritoglu, Can; Miller, Michael; Mori, Susumu; Lu, Hanzhang; 74141364 (Park, DC); Park, Denise C.; Rodrigue, Karen M.Arterial spin labeling (ASL) MRI is increasingly used in research and clinical settings. The purpose of this work is to develop a cloud-based tool for ASL data processing, referred to as ASL-MRICloud, which may be useful to the MRI community. In contrast to existing ASL toolboxes, which are based on software installation on the user's local computer, ASL-MRICloud uses a web browser for data upload and results download, and the computation is performed on the remote server. As such, this tool is independent of the user's operating system, software version, and CPU speed. The ASL-MRICloud tool was implemented to be compatible with data acquired by scanners from all major MRI manufacturers, is capable of processing several common forms of ASL, including pseudo-continuous ASL and pulsed ASL, and can process single-delay and multi-delay ASL data. The outputs of ASL-MRICloud include absolute and relative values of cerebral blood flow, arterial transit time, voxel-wise masks indicating regions with potential hyper-perfusion and hypo-perfusion, and an image quality index. The ASL tool is also integrated with a T₁-based brain segmentation and normalization tool in MRICloud to allow generation of parametric maps in standard brain space as well as region-of-interest values. The tool was tested on a large data set containing 309 ASL scans as well as on publicly available ASL data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study.Item Decreased Segregation of Brain Systems across the Healthy Adult Lifespan(National Academy of Science) Chan, Micaela Y.; Park, Denise C.; Savalia, Neil K.; Petersen, Steven E.; Wig, Gagan S.; 0000 0000 0265 9301 (Park, DC); 92048764 (Park, DC); 74141364 (Park, DC)Healthy aging has been associated with decreased specialization in brain function. This characterization has focused largely on describing age-accompanied differences in specialization at the level of neurons and brain areas. We expand this work to describe systems-level differences in specialization in a healthy adult lifespan sample (n = 210; 20-89 y). A graph-theoretic framework is used to guide analysis of functional MRI resting-state data and describe systems-level differences in connectivity of individual brain networks. Young adults' brain systems exhibit a balance of within-and between-system correlations that is characteristic of segregated and specialized organization. Increasing age is accompanied by decreasing segregation of brain systems. Compared with systems involved in the processing of sensory input and motor output, systems mediating "associative" operations exhibit a distinct pattern of reductions in segregation across the adult lifespan. Of particular importance, the magnitude of association system segregation is predictive of long-term memory function, independent of an individual's age.Item Estimation of Brain Functional Connectivity from Hypercapnia BOLD MRI Data: Validation in a Lifespan Cohort of 170 Subjects(Academic Press Inc Elsevier Science, 2018-11-16) Hou, Xirui; Liu, Peiying; Gu, Hong; Chan, Micaela; Li, Yang; Peng, Shin-Lei; Wig, Gagan; Yang, Yihong; Park, Denise C.; Lu, Hanzhang; 74141364 (Park, DC); Chan, Micaela; Park, Denise C.Functional connectivity MRI, based on Blood-Oxygenation-Level-Dependent (BOLD) signals, is typically performed while the subject is at rest. On the other hand, BOLD is also widely used in physiological imaging such as cerebrovascular reactivity (CVR) mapping using hypercapnia (HC) as a modulator. We therefore hypothesize that hypercapnia BOLD data can be used to extract FC metrics after factoring out the effects of the physiological modulation, which will allow simultaneous assessment of neural and vascular function and may be particularly important in populations such as aging and cerebrovascular diseases. The present work aims to systematically examine the feasibility of hypercapnia BOLD-based FC mapping using three commonly applied analysis methods, specifically dual-regression Independent Component Analysis (ICA), region-based FC matrix analysis, and graph-theory based network analysis, in a large cohort of 170 healthy subjects ranging from 20 to 88 years old. To validate the hypercapnia BOLD results, we also compared these FC metrics with those obtained from conventional resting-state data. ICA analysis of the hypercapnia BOLD data revealed FC maps that strongly resembled those reported in the literature. FC matrix using region-based analysis showed a correlation of 0.97 on the group-level and 0.54 ± 0.10 on the individual-level, when comparing between hypercapnia and resting-state results. Although the correspondence on the individual-level was moderate, this was primarily attributed to variations intrinsic to FC mapping, because a corresponding resting-vs-resting comparison in a sub-cohort (N = 39) revealed a similar correlation of 0.57 ± 0.09. Graph-theory computations were also feasible in hypercapnia BOLD data and indices of global efficiency, clustering coefficient, modularity, and segregation were successfully derived. Hypercapnia FC results revealed age-dependent differences in which within-network connections generally exhibited an age-dependent decrease while between-network connections showed an age-dependent increase.Item Functional Activity Features in Successful Cognitive Aging(2019-12) Chen, Xi; 0000-0003-1998-8461 (Chen, X); Park, Denise C.Cognitive aging research has traditionally studied the inevitable cognitive decline in older adults as a group. Recently, more research has recognized the importance of understanding the individual variability in cognitive aging trajectories. Some individuals show superior performance and better preservation of cognition relative to others at their age, termed “prime” agers in the present dissertation. By contrast, some individuals may exhibit substantial cognitive deficits and greater decline representing a suboptimal cognitive aging profile, termed “nonprime” individuals. Many neuroimaging research efforts have been made to explore the neural mechanisms associated with these individual differences. Two possible patterns of functional activity, youth-like activation and compensatory recruitment, have been proposed to be particularly related to individual variability in cognitive changes. However, there is still a lack of consensus on what brain activity patterns may represent optimal aging in prime individuals. The present dissertation investigated this question in two studies. Because one major source of difficulty in this topic is the challenge in identifying prime agers, Study 1 implemented an exploratory data-driven approach to classify participants based on their cognitive performance and longitudinal cognitive change across multiple cognitive domains. Using two waves of longitudinal cognitive data (with a four-year interval) in episodic memory, inductive reasoning, working memory, processing speed from the Dallas Lifespan Brain Study, Study 1 in Chapter 2 examined the cognitive aging profiles in middle-aged, young-old and very old participants, and successfully identified two distinct cognitive aging profiles among participants, representing prime and nonprime individuals. Study 2 in Chapter 3 then utilized this classification of subgroups and compared their patterns of functional activity using a subsequent memory fMRI task collected at the second wave of DLBS. The analyses revealed several functional activity pattern differences between prime and nonprime individuals. First, prime individuals showed greater subsequent memory effect than nonprime individuals across core task-related regions associated with successful encoding. In addition, the higher subsequent memory effect in prime individuals, compared to nonprime individuals, was most evident in the young-old group, because prime agers exhibited better preservation of higher effect comparable to in younger adults, until very old age. In contrast, nonprime agers showed reduced subsequent memory effect starting in young-old age. Finally, prime young-old adults also recruited additional frontal regions, including left superior frontal and right orbitofrontal cortex, compared to young adults. This additional recruitment showed a trend of relationship to better memory performance, possibly suggesting a compensatory nature of this activation. In conclusion, the present dissertation demonstrated the use of a data-driven, multivariate approach and successfully identified prime and nonprime agers with distinct cognitive aging profiles. Comparison of their patterns of functional brain activity revealed that prime agers show a preservation of higher activation until very late in the lifespan and additional frontal recruitment in young-old age.Item Investigating Unique Environmental Contributions to the Neural Representation of Written Words: A Monozygotic Twin StudyPark, J.; Park, Denise C.; Polk, T. A.; 0000 0000 0265 9301 (Park, DC); 92048764 (Park, DC)The visual word form area (VWFA) is a region of left inferior occipitotemporal cortex that is critically involved in visual word recognition. Previous studies have investigated whether and how experience shapes the functional characteristics of VWFA by comparing neural response magnitude in response to words and nonwords. Conflicting results have been obtained, however, perhaps because response magnitude can be influenced by other factors such as attention. In this study, we measured neural activity in monozygotic twins, using functional magnetic resonance imaging. This allowed us to quantify differences in unique environmental contributions to neural activation evoked by words, pseudowords, consonant strings, and false fonts in the VWFA and striate cortex. The results demonstrate significantly greater effects of unique environment in the word and pseudoword conditions compared to the consonant string and false font conditions both in VWFA and in left striate cortex. These findings provide direct evidence for environmental contributions to the neural architecture for reading, and suggest that learning phonology and/or orthographic patterns plays the biggest role in shaping that architecture. © 2012 Park et al.Item Michigan Neural Distinctiveness (MiND) Study Protocol: Investigating the Scope, Causes, and Consequences of Age-Related Neural Dedifferentiation(BioMed Central Ltd.) Gagnon, H.; Simmonite, M.; Cassady, K.; Chamberlain, J.; Freiburger, E.; Lalwani, P.; Kelley, S.; Foerster, B.; Park, Denise C.; Petrou, M.; Seidler, R. D.; Taylor, S. F.; Weissman, D. H.; Polk, T. A.; 74141364 (Park, DC); Park, Denise C.Background: Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). Methods: The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. Discussion: By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. Trial registration: This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136. © 2019 The Author(s).Item Resting-State Network Topology Differentiates Task Signals across the Adult Life Span(Society for Neuroscience) Chan, Micaela Y.; Alhazmi, Fahd H.; Park, Denise C.; Savalia, Neil K.; Wig, Gagan S.; Chan, Micaela Y.; Alhazmi, Fahd H.; Park, Denice C.; Savalia, Neil K.; Wig, Gagan S.Brain network connectivity differs across individuals. For example, older adults exhibit less segregated resting-state subnetworks relative to younger adults (Chan et al., 2014). It has been hypothesized that individual differences in network connectivity impact the recruitment of brain areas during task execution. While recent studies have described the spatial overlap between resting-state functional correlation (RSFC) sub-networks and task-evoked activity, it is unclear whether individual variations in the connectivity pattern of a brain area (topology) relates to its activity during task execution. We report data from 238 cognitively normal participants (humans), sampled across the adult life span (20-89 years), to reveal that RSFC-based network organization systematically relates to the recruitment of brain areas across two functionally distinct tasks (visual and semantic). The functional activity of brain areas (network nodes) were characterized according to their patterns of RSFC: nodes with relatively greater connections to nodes in their own functional system (“non-connector” nodes) exhibited greater activity than nodes with relatively greater connections to nodes in other systems (“connector” nodes). This “activation selectivity” was specific to those brain systems that were central to each of the tasks. Increasing age was accompanied by less differentiated network topology and a corresponding reduction in activation selectivity (or differentiation) across relevant network nodes. The results provide evidence that connectional topology of brain areas quantified at rest relates to the functional activity of those areas during task. Based on these findings, we propose a novel network-based theory for previous reports of the “dedifferentiation” in brain activity observed in aging.Item Sensorimotor Network Segregation Declines with Age and is Linked to GABA and to Sensorimotor Performance(Academic Press Inc Elsevier Science, 2018-11-09) Cassady, Kaitlin; Gagnon, Holly; Lalwani, Poortata; Simmonite, Molly; Foerster, Bradley; Park, Denise C.; Peltier, Scott J.; Petrou, Myria; Taylor, Stephan F.; Weissman, Daniel H.; Seidler, Rachael D.; Polk, Thad A.; 74141364 (Park, DC); Park, Denise C.Aging is typically associated with declines in sensorimotor performance. Previous studies have linked some age-related behavioral declines to reductions in network segregation. For example, compared to young adults, older adults typically exhibit weaker functional connectivity within the same functional network but stronger functional connectivity between different networks. Based on previous animal studies, we hypothesized that such reductions of network segregation are linked to age-related reductions in the brain's major inhibitory transmitter, gamma aminobutyric acid (GABA). To investigate this hypothesis, we conducted graph theoretical analyses of resting state functional MRI data to measure sensorimotor network segregation in both young and old adults. We also used magnetic resonance spectroscopy to measure GABA levels in the sensorimotor cortex and collected a battery of sensorimotor behavioral measures. We report four main findings. First, relative to young adults, old adults exhibit both less segregated sensorimotor brain networks and reduced sensorimotor GABA levels. Second, less segregated networks are associated with lower GABA levels. Third, less segregated networks and lower GABA levels are associated with worse sensorimotor performance. Fourth, network segregation mediates the relationship between GABA and performance. These findings link age-related differences in network segregation to age-related differences in GABA levels and sensorimotor performance. More broadly, they suggest a neurochemical substrate of age-related dedifferentiation at the level of large-scale brain networks.Item Socioeconomic Status Moderates Age-Related Differences in the Brain's Functional Network Organization and Anatomy Across the Adult LifespanChan, Micaela Y.; Na, Jinkyung; Agres, Phillip F.; Savalia, Neil K.; Park, Denise C.; Wig, Gagan S.; 74141364 (Park, DC); Chan, Micaela Y.; Agres, Phillip F.; Savalia, Neil K.; Park, Denise C.; Wig, Gagan S.An individual's environmental surroundings interact with the development and maturation of their brain. An important aspect of an individual's environment is his or her socioeconomic status (SES), which estimates access to material resources and social prestige. Previous characterizations of the relation between SES and the brain have primarily focused on earlier or later epochs of the lifespan (i.e., childhood, older age). We broaden this work to examine the relationship between SES and the brain across a wide range of human adulthood (20-89 years), including individuals from the less studied middle-age range. SES, defined by education attainment and occupational socioeconomic characteristics, moderates previously reported age-related differences in the brain's functional network organization and whole-brain cortical structure. Across middle age (35-64 years), lower SES is associated with reduced resting-state system segregation (a measure of effective functional network organization). A similar but less robust relationship exists between SES and age with respect to brain anatomy: Lower SES is associated with reduced cortical gray matter thickness in middle age. Conversely, younger and older adulthood do not exhibit consistent SES-related difference in the brain measures. The SES-brain relationships persist after controlling for measures of physical and mental health, cognitive ability, and participant demographics. Critically, an individual's childhood SES cannot account for the relationship between their current SES and functional network organization. These findings provide evidence that SES relates to the brain's functional network organization and anatomy across adult middle age, and that higher SES may be a protective factor against age-related brain decline.Item Task Learning as a Mechanism of Transfer in Cognitive Intervention: Neuro-cognitive Predictors and Outcomes of Early, Middle and Late Stages of Task Learning(2021-12-01T06:00:00.000Z) Smith, Evan Taylor; Kilgard, Michael P.; Basak, Chandramallika; Park, Denise C.; Fishwick, Paul; Evans, JuliaInvestigation into methods of addressing cognitive loss exhibited later in life is of paramount importance to the field of cognitive aging. The passive protective factors of cognitive reserve and continued education, as well as the active factor of cognitive intervention, have all been found to ameliorate expected declines in cognition in adults aged sixty-five and up, and all three of these factors heavily involve the learning process. This dissertation presents three studies derived from a longitudinal cognitive intervention, each designed to illuminate factors which influence the learning process and in turn how that process bolsters cognition. The cognitive intervention in question was a working-memory-based video-game-like training task, designed to be both engaging and adaptive to the abilities of individual participants. The first study identified a measure of verbal episodic memory as well as the volume of a brain region involved in language, verbal memory and cognitive control (the left inferior frontal gyrus) as predictors of individual learning rates on the training task. These two neuro-cognitive measures were more predictive of task learning when considered in conjunction than when considered separately, indicating a complimentary effect. The second study compared daily performance on the training task with several daily factors known to influence cognition, including perceived wellbeing, stress, business, and sleep. Auto-regressive analyses conducted in Study 2 were able to identify meaningful predictors of performance-over-time on the training task in fifty percent of cases. This pattern of influences varied greatly between participants, indicating a highly individualized influence of these variables. The third study observed that individual differences in learning of the training task were related to training-related gains in a measure of nonverbal reasoning, with participants who learned the training task faster showing relatively greater transfer (i.e. gains) to that measure of reasoning. Collectively, the three studies presented in this dissertation offer a novel insight into training-related cognitive benefits via the identification of a discreet “path of transfer” resultant from this training. Specifically, these studies identify a pattern of influence by which verbal episodic memory (and its related brain region) is determinant of learning of a working-memory task (the training task), and learning of that task itself is determinant of training-related gains to nonverbal reasoning. This pattern of findings serves as a testable hypothesis for future studies of working-memory based cognitive training in older adults, and this “path of transfer” approach may serve as a useful tool in examining the concept of transfer more generally.