Browsing by Author "Wig, Gagan"
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Item Effects of Transcranial Magnetic Stimulation on Individual Functional Brain Networks(2022-12-01T06:00:00.000) Agres, Phillip Frederick 1990-; Wig, Gagan; Rodrigue, Karen; Kennedy, Kristen; Hart Jr., John; Rugg, Michael D.Transcranial magnetic stimulation (TMS) has long been utilized as a tool to non-invasively study the association between brain function and cognition and is increasingly being used as a therapeutic intervention to modify brain function in an effort to treat disease. Towards these goals, recent efforts have strived to target and modify large-scale functional brain networks. This work is predicated on observations that the organization of the human functional brain network is related to behavioral performance among individuals across the lifespan, and cognitive decline that has been observed in health aging and in disease states. Large-scale brain networks consist of nodes (brain areas) that vary in their functional characteristics. Nodes belong to distinct subnetworks that represent functional brain systems related to cognition and sensory-motor function. Functional brain network organization has been observed to differ in specific topography and localization across individuals, which motivates efforts towards identifying individual-specific stimulation targets to reduce group-level bias and inaccuracies. This dissertation project utilized resting-state functional correlations (RSFC) to map the functional brain networks of individuals and identify specific stimulation targets in a group of healthy young adult participants (N = 17[9F], 18-30y). RSFC MRI was collected at baseline and 24 hours after completing a 5-day high-frequency rTMS protocol. For each individual participant, two cortical stimulation targets with distinct functional and topological properties were identified: the left angular gyrus (L. Ang.) and left middle frontal gyrus (L. MFG), with each target serving as an active control condition for the other target. On-target stimulation of each cortical target resulted in RSFC changes between the respective target node and its connections in the network, whereas RSFC changes were less evident following off-target (control-site) stimulation. RSFC changes were demonstrated to be related to the baseline RSFC strength and Euclidean distance between each target and their respective network connections, and was also related to on-target stimulation, demonstrating distal impacts of TMS that are mediated by both functional and anatomical features of functionally connected brain regions. On-target TMS to the L. Ang. decreased RSFC within the default-mode system (DMN) and on-target TMS to the L. MFG decreased RSFC within the frontoparietal control system (FPN) as well as in the default- mode system; off-target control stimulation had no impact on RSFC within the DMN. While node-level and system-level correlations were modified as a result of TMS, system segregation, an overall measure quantifying brain network organization was not impacted by TMS, highlighting the potential resiliency of a segregated brain network in the face of TMS perturbation. Notably, measures of episodic memory performance (but also fluid ability and working memory) were not impacted by TMS and were not related to observed changes in RSFC, despite previous reports that have provided evidence for these effects. This dissertation provides evidence that individualized on-target TMS modifies RSFC in a target-specific manner and is related to functional properties of the stimulated node within the brain network.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 fNIRS and Pupillometry Correlates of Attentional States(2020-12-01T06:00:00.000Z) Gunal, Mehmet; Krawczyk, Daniel; Evans, Julia; Liu, Hanli; Rypma, Bart; Wig, GaganThis dissertation aims to examine the localization and function of BA 10 specifically looking into its role in maintaining and switching between attentional states using functional near-infrared spectroscopy (fNIRS) and pupillometry. Previous findings from fMRI report a medial-lateral BA10 dissociation during stimulus-oriented (SO) and stimulus-independent (SI) tasks. Pupillometry has been previously used to investigate different attention states, dissociating focused, attention (on-task) trials from mind-wandered, distracted (off-task) states. However, so far there is no evidence that fNIRS hemodynamic responses (HR) and pupillary responses (PR) could be used to better characterize and identify attention states. Replacing fMRI with fNIRS, I divided SO and SI tasks into on-task and off-task groups and showed that fNIRS exhibit similar medial-lateral BA10 dissociations for SO tasks. I also showed that both HR and PR can be used to distinguish on-task SO from off-task SO groups. Finally, I explored whether fNIRS and pupillometry signals share similar biomarkers which may enhance the identification of these attention states using these measures simultaneously. This study was able to successfully characterize attention states and dissociate them on BA10 but did not confirm that simultaneous signal acquisition of these two methods would enhance the identification of attentional states.Item The Relationship Between Age, Cognitive Performance, and the Neural Correlates of Episodic Memory Encoding and Retrieval(2022-12-01T06:00:00.000Z) Srokova, Sabina 1995-; Wig, Gagan; Rugg, Michael D.; Seaman, Kendra; Kennedy, Kristen; O'Toole, Alice J.Cognitive aging is associated with a disproportionate decline in episodic memory, the ability to recollect contextual details of previously experienced events. Understanding the mechanisms which underlie age-related episodic memory decline is a critical precursor to developing interventions aimed at ameliorating memory deficits in healthy and pathological aging. Considerable empirical evidence suggests that age-related episodic memory deficits arise from numerous factors which differentially impact multiple neural processes and brain regions. The present work focuses on examining some contributors which have been proposed under this framework. Study 1 investigates age-related neural dedifferentiation, a phenomenon characterized by age-related reductions in the neural selectivity of category-selective cortical regions. Our analyses reveal robust age effects on neural differentiation for scene, but not for face stimuli, adding to prior evidence indicating that age-related neural dedifferentiation is not a ubiquitous phenomenon. Study 1 also reveals that the strength of neural differentiation during encoding is predictive of subsequent memory performance independently of age. The work in Study 1 is complemented by Study 4 in which neural dedifferentiation is operationalized at the level of individual exemplars (as opposed to stimulus categories). To examine item-level neural differentiation, we framed our analyses in terms of age differences in repetition suppression effects, which revealed null effects of age. Collectively, Studies 1 and 4 highlighting the functional significance of age-related neural dedifferentiation and emphasize the urgent need to advance our understanding of the factors that lead to age differences in neural selectivity and specificity. Moving on to Study 2, the work described therein examines age differences in retrieval gating, the ability to regulate the retrieval of mnemonic information according to behavioral goals. Study 2 provides the first evidence that older adults do not engage in retrieval gating, indicating that episodic memory decline may arise as consequence of a decline in the engagement of goal- dependent retrieval strategies. Lastly, Study 3 reveals novel evidence for age differences in the retrieval-related anterior shift, the phenomenon whereby the peak neural activity at retrieval occurs in more anterior portions of single cortical regions relative to encoding. Our analyses show that the shift is greater in older than younger adults, and that greater shift is associated with worse memory performance independently of age. In line with prior empirical work proposing a posterior (perceptual) to anterior (conceptual) gradient in the brain, these findings indicate that the age- related increase in anterior shift may be reflective of an increased reliance on gist-based low- fidelity retrieval in older age. Taken together, the studies comprising this dissertation enhance our understanding of the behavioral and neural correlates of cognitive aging and advance the collective knowledge in the field cognitive neuroscience of age-related episodic memory decline.Item Time-varying Sources and Vascular Contributions to Age-accompanied Functional Brain Network Re-organization(2022-12-01T06:00:00.000Z) Han, Liang; Wig, Gagan; Stillman, Robert D; Rugg, Michael D.; Rypma, Bart; Gel, YuliaThe brain is a complex network of interacting brain areas that can be further divided into segregated functional systems. Resting-state system segregation is a feature of brain network organization that has relevance to brain function in both health and disease across adult lifespan. It is unclear what gives rise to system segregation and the individual differences in this brain network measure. In this dissertation, two aspects of this important question are investigated: (1) Do vascular factors contribute to relationships between age and system segregation across the adult lifespan? and (2) Can sources of time-varying information help account for relationships between aging and system segregation? The interplay between these questions reveals how the temporal evolution of system re-configuration at a short time scale impacts more stable individual features of large-scale network organization, in the context of differences in vascular health of adult individuals. This dissertation was accomplished by incorporating data from a total of 894 unique participants, over 3 independent studies (age range: 20 – 100 years) and including multiple neuroimaging modalities and measures of participant health and demographics. The contribution of vascular factors towards relationships between age and resting-state system segregation is first investigated. There exist relationships between age and vascular measures, including cardiovascular health (CVH) and cerebrovascular reactivity (CVR). Age-related decreases of system segregation persist after controlling for vascular-related variance. This is demonstrated by (i) computing system segregation regional CVR-corrected signals within each participant, and (ii) including CVH as a participant-level covariate in the models. These results demonstrate that age-related differences in system segregation cannot be fully attributed to differences in cerebrovascular and cardiovascular factors. To examine the contribution of time-varying information to system segregation, I examine the relationship between resting-state BOLD signal variability and system segregation. After controlling for vascular confounds by (i) estimating BOLD variability using CVR-corrected signals, (ii) including CVH as a covariate in the model, there is an absence of a relationship between age and BOLD variability, revealing that vascular factors serve as a major source of variance explaining previously reported relationships between age and resting-state BOLD signal variability. Further, with correction of vascular factors, BOLD variability does not relate to system segregation. An additional source of time-varying information is evaluated in relation to system segregation, focused on co-fluctuation amplitude of the resting-state time-series. Moments of greater co- fluctuation pattern across edges are identified (events), during which functional brain networks are highly modular relative to non-event moments. I demonstrate that the number of events that are present in an individual’s resting-state time-series is related to their system segregation. However, I next demonstrate that age-accompanied decreases of system segregation are evident across all the moments, irrespective of co-fluctuation amplitude of edges. Collectively, these findings reveal that while high co-fluctuation moments (events) may contribute towards establishing an individual’s system segregation, brain network re-organization exists across all time points of a resting-state scan. In sum, this dissertation provides important support that resting-state system segregation measures brain network re-organization across the adult lifespan. This measure is independent from vascular differences within individuals, and provides critical evidence of brain aging that is consistently evident across periods of rest. Serving as a biomarker of functional brain network integrity, system segregation further supports the application of this approach towards measuring individual brain health across the lifespan.