Park, Denise C.

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Dr. Denise Park is the Co-director and Founder of the Center for Vital Longevity She is a Regents' Research Scholar and professor of behavioral and brain sciences. Dr. Park holds the Distinguished University Chair in Behavioral and Brain Sciences. Dr. Park focuses her research program on understanding how the mind changes and adapts as we age.

Learn more about Denise Park on her BBS People, the Park Aging Mind Laboratory and Research Explorer pages.


Recent Submissions

Now showing 1 - 9 of 9
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    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.
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    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.
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    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.
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    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).
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    Socioeconomic Status Moderates Age-Related Differences in the Brain's Functional Network Organization and Anatomy Across the Adult Lifespan
    Chan, 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.
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    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.
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    The Role of Cognitive Function in the Relationship between Age and Health Literacy: A Cross-Sectional Analysis of Older Adults in Chicago, USA
    (BMJ Publishing Group Ltd) Kobayashi, Lindsay C.; Smith, Samuel G.; O'Conor, Rachel; Curtis, Laura M.; Park, Denise C. (UT Dallas); von Wagner, Christian; Deary, Ian J.; Wolf, Michael S.
    Objectives: To investigate how 3 measures of health literacy correlate with age and the explanatory roles of fluid and crystallised cognitive abilities in these relationships among older adults.; Design: Cross-sectional baseline analysis of the 'LitCog' cohort study.; Setting: 1 academic internal medicine clinic and 5 federally qualified health centres in Chicago, USA.; Participants: English-speaking adults (n=828) aged 55-74 years, recruited from August 2008 through October 2011.; Outcome Measures: Health literacy was measured by the Test of Functional Health Literacy in Adults (TOFHLA) and the Newest Vital Sign (NVS), both of which assess reading comprehension and numeracy in health contexts, and by the Rapid Estimate of Adult Literacy in Medicine (REALM), which assesses medical vocabulary. Fluid cognitive ability was assessed through the cognitive domains of processing speed, inductive reasoning, and working, prospective and long-term memories, and crystallised cognitive ability through the verbal ability domain.; Results: TOFHLA and NVS scores were lower at ages 70-74 years compared with all other age groups (p < 0.05 for both tests). The inverse association between age and TOFHLA score was attenuated from ß=-0.39 (95% CI -0.55 to -0.22) to ß=-0.06 (95% CI -0.20 to 0.08) for ages 70-74 vs 55-59 years when fluid cognitive ability was added to the model (85% attenuation). Similar results were seen with NVS scores (68% attenuation). REALM scores did not differ by age group (p=0.971). Crystallised cognitive ability was stable across age groups, and did not influence the relationships between age and TOFHLA or NVS performance.; Conclusions: Health literacy skills show differential patterns of age-related change, which may be explained by cognitive ageing. Researchers should select health literacy tests appropriate for their purposes when assessing the health literacy of older adults. Clinicians should be aware of this issue to ensure that health self-management tasks for older patients have appropriate cognitive and literacy demands.
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    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.
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    Investigating Unique Environmental Contributions to the Neural Representation of Written Words: A Monozygotic Twin Study
    Park, 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.

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