Christian received his Bachelor’s Degree at the University of California, Berkeley, where he developed his initial interest in functional brain imaging at the Helen Wills Neuroscience Institute with the D’Esposito Lab. He later attended the University of Wisconsin-Madison for his graduate studies and obtained his Doctorate Degree in the Neurosciences focusing on frequency analysis of the intrinsic low-frequency oscillation of the resting-state in populations of aging and ischemic stroke using rs-fMRI.
Currently, Christian is interested in the characterization of cortical system disruption in Parkinson’s disease population, in terms of functional network interactions and dynamics of the network connectivity.
Honors & Awards
Biological Sciences Scholar Award, University of Wisconsin-Madison The Graduate School (May 2011)
NTP Training Fellowship, University of Wisconsin-Madison NTP (Aug 2011--Jul 2012)
ICTR Pre-doctoral Training Fellowship, University of Wisconsin-Madison ICTR (Sept 2012--Jun 2014)
CNTP Training Fellowship, University of Wisconsin-Madison CNTP (Jul 2014--June 2016)
Bachelor of Art, University of California Berkeley, Biology - Neurobiology (2005)
Doctor of Philosophy, University of Wisconsin Madison (2015)
Kathleen Poston, Postdoctoral Faculty Sponsor
Implication of the Slow-5 Oscillations in the Disruption of the Default-Mode Network in Healthy Aging and Stroke.
2016; 6 (6): 482–95
The processes of normal aging and aging-related pathologies subject the brain to an active re-organization of its brain networks. Among these, the default-mode network (DMN) is consistently implicated with a demonstrated reduction in functional connectivity within the network. However, no clear stipulation on the underlying mechanisms of the de-synchronization has yet been provided. In this study, we examined the spectral distribution of the intrinsic low-frequency oscillations (LFOs) of the DMN sub-networks in populations of young normals, older subjects, and acute and subacute ischemic stroke patients. The DMN sub-networks were derived using a mid-order group independent component analysis with 117 eyes-closed resting-state functional magnetic resonance imaging (rs-fMRI) sessions from volunteers in those population groups, isolating three robust components of the DMN among other resting-state networks. The posterior component of the DMN presented noticeable differences. Measures of amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) of the network component demonstrated a decrease in resting-state cortical oscillation power in the elderly (normal and patient), specifically in the slow-5 (0.01-0.027 Hz) range of oscillations. Furthermore, the contribution of the slow-5 oscillations during the resting state was diminished for a greater influence of the slow-4 (0.027-0.073 Hz) oscillations in the subacute stroke group, not only suggesting a vulnerability of the slow-5 oscillations to disruption but also indicating a change in the distribution of the oscillations within the resting-state frequencies. The reduction of network slow-5 fALFF in the posterior DMN component was found to present a potential association with behavioral measures, suggesting a brain-behavior relationship to those oscillations, with this change in behavior potentially resulting from an altered network integrity induced by a weakening of the slow-5 oscillations during the resting state. The repeated identification of those frequencies in the disruption of DMN stresses a critical role of the slow-5 oscillations in network disruption, and it accentuates the importance of managing those oscillations in the health of the DMN.
View details for DOI 10.1089/brain.2015.0375
View details for PubMedID 27130180
Differing Patterns of Altered Slow-5 Oscillations in Healthy Aging and Ischemic Stroke.
Frontiers in human neuroscience
2016; 10: 156
The 'default-mode' network (DMN) has been investigated in the presence of various disorders, such as Alzheimer's disease and Autism spectrum disorders. More recently, this investigation has expanded to include patients with ischemic injury. Here, we characterized the effects of ischemic injury in terms of its spectral distribution of resting-state low-frequency oscillations and further investigated whether those specific disruptions were unique to the DMN, or rather more general, affecting the global cortical system. With 43 young healthy adults, 42 older healthy adults, 14 stroke patients in their early stage (<7 days after stroke onset), and 16 stroke patients in their later stage (between 1 to 6 months after stroke onset), this study showed that patterns of cortical system disruption may differ between healthy aging and following the event of an ischemic stroke. The stroke group in the later stage demonstrated a global reduction in the amplitude of the slow-5 oscillations (0.01-0.027 Hz) in the DMN as well as in the primary visual and sensorimotor networks, two 'task-positive' networks. In comparison to the young healthy group, the older healthy subjects presented a decrease in the amplitude of the slow-5 oscillations specific to the components of the DMN, while exhibiting an increase in oscillation power in the task-positive networks. These two processes of a decrease DMN and an increase in 'task-positive' slow-5 oscillations may potentially be related, with a deficit in DMN inhibition, leading to an elevation of oscillations in non-DMN systems. These findings also suggest that disruptions of the slow-5 oscillations in healthy aging may be more specific to the DMN while the disruptions of those oscillations following a stroke through remote (diaschisis) effects may be more widespread, highlighting a non-specificity of disruption on the DMN in stroke population. The mechanisms underlying those differing modes of network disruption need to be further explored to better inform our understanding of brain function in healthy individuals and following injury.
View details for DOI 10.3389/fnhum.2016.00156
View details for PubMedID 27148013
Recovery of slow-5 oscillations in a longitudinal study of ischemic stroke patients.
2016; 11: 398-407
Functional networks in resting-state fMRI are identified by characteristics of their intrinsic low-frequency oscillations, more specifically in terms of their synchronicity. With advanced aging and in clinical populations, this synchronicity among functionally linked regions is known to decrease and become disrupted, which may be associated with observed cognitive and behavioral changes. Previous work from our group has revealed that oscillations within the slow-5 frequency range (0.01-0.027 Hz) are particularly susceptible to disruptions in aging and following a stroke. In this study, we characterized longitudinally the changes in the slow-5 oscillations in stroke patients across two different time-points. We followed a group of ischemic stroke patients (n = 20) and another group of healthy older adults (n = 14) over two visits separated by a minimum of three months (average of 9 months). For the stroke patients, one visit occurred in their subacute window (10 days to 6 months after stroke onset), the other took place in their chronic window (> 6 months after stroke). Using a mid-order group ICA method on 10-minutes eyes-closed resting-state fMRI data, we assessed the frequency distributions of a component's representative time-courses for differences in regards to slow-5 spectral power. First, our stroke patients, in their subacute stage, exhibited lower amplitude slow-5 oscillations in comparison to their healthy counterparts. Second, over time in their chronic stage, those same patients showed a recovery of those oscillations, reaching near equivalence to the healthy older adult group. Our results indicate the possibility of an eventual recovery of those initially disrupted network oscillations to a near-normal level, providing potentially a biomarker for stroke recovery of the cortical system. This finding opens new avenues in infra-slow oscillation research and could serve as a useful biomarker in future treatments aimed at recovery.
View details for DOI 10.1016/j.nicl.2016.03.008
View details for PubMedID 27077023
Age-Related Changes in BOLD Activation Pattern in Phonemic Fluency Paradigm: An Investigation of Activation, Functional Connectivity and Psychophysiological Interactions.
Frontiers in aging neuroscience
2016; 8: 110
Healthy aging is associated with decline of cognitive functions. However, even before those declines become noticeable, the neural architecture underlying those mechanisms has undergone considerable restructuring and reorganization. During performance of a cognitive task, not only have the task-relevant networks demonstrated reorganization with aging, which occurs primarily by recruitment of additional areas to preserve performance, but the task-irrelevant network of the "default-mode" network (DMN), which is normally deactivated during task performance, has also consistently shown reduction of this deactivation with aging. Here, we revisited those age-related changes in task-relevant (i.e., language system) and task-irrelevant (i.e., DMN) systems with a language production paradigm in terms of task-induced activation/deactivation, functional connectivity, and context-dependent correlations between the two systems. Our task fMRI data demonstrated a late increase in cortical recruitment in terms of extent of activation, only observable in our older healthy adult group, when compared to the younger healthy adult group, with recruitment of the contralateral hemisphere, but also other regions from the network previously underutilized. Our middle-aged individuals, when compared to the younger healthy adult group, presented lower levels of activation intensity and connectivity strength, with no recruitment of additional regions, possibly reflecting an initial, uncompensated, network decline. In contrast, the DMN presented a gradual decrease in deactivation intensity and deactivation extent (i.e., low in the middle-aged, and lower in the old) and similar gradual reduction of functional connectivity within the network, with no compensation. The patterns of age-related changes in the task-relevant system and DMN are incongruent with the previously suggested notion of anti-correlation of the two systems. The context-dependent correlation by psycho-physiological interaction (PPI) analysis demonstrated an independence of these two systems, with the onset of task not influencing the correlation between the two systems. Our results suggest that the language network and the DMN may be non-dependent systems, potentially correlated through the re-allocation of cortical resources, and that aging may affect those two systems differently.
View details for DOI 10.3389/fnagi.2016.00110
View details for PubMedID 27242519
Age-Related Changes in Inter-Network Connectivity by Component Analysis
FRONTIERS IN AGING NEUROSCIENCE
Healthy aging is associated with brain changes that reflect an alteration to a functional unit in response to the available resources and architecture. Even before the onset of noticeable cognitive decline, the neural scaffolds underlying cognitive function undergo considerable change. Prior studies have suggested a disruption of the connectivity pattern within the "default-mode" network (DMN), and more specifically a disruption of the anterio-posterior connectivity. In this study, we explored the effects of aging on within-network connectivity of three DMN subnetworks: a posterior DMN (pDMN), an anterior DMN (aDMN), and a ventral DMN (vDMN); as well as between-network connectivity during resting-state. Using groupICA on 43 young and 43 older healthy adults, we showed a reduction of network co-activation in two of the DMN subnetworks (pDMN and aDMN) and demonstrated a difference in between-component connectivity levels. The older group exhibited more numerous high-correlation pairs (Pearson's rho > 0.3, Number of comp-pairs = 46) in comparison to the young group (Number of comp-pairs = 34), suggesting a more connected/less segregated cortical system. Moreover, three component-pairs exhibited statistically significant differences between the two populations. Visual areas V2-V1 and V2-V4 were more correlated in the older adults, while aDMN-pDMN correlation decreased with aging. The increase in the number of high-correlation component-pairs and the elevated correlation in the visual areas are consistent with the prior hypothesis that aging is associated with a reduction of functional segregation. However, the aDMN-pDMN dis-connectivity may be occurring under a different mechanism, a mechanism more related to a breakdown of structural integrity along the anterio-posterior axis.
View details for DOI 10.3389/fnagi.2015.00237
View details for Web of Science ID 000367229500001
View details for PubMedID 26733864
Regional homogeneity (ReHo) changes in new onset versus chronic benign epilepsy of childhood with centrotemporal spikes (BECTS): A resting state fMRI study
2015; 116: 79-85
The purpose of this study was to investigate regional homogeneity (ReHo) in children with new-onset drug-naïve Benign Epilepsy with Centrotemporal Spikes (BECTS), chronic BECTS and healthy controls (HC) using the Regional Homogeneity (ReHo) method applied to resting state fMRI data.Resting state fMRI data was collected from three groups of children aged 6-13, including new onset drug naïve BECTS, chronic BECTS with medication, and HC; the data analyzed by ReHo method. Mandarin school exams scores were acquired and compared across groups.There were three main findings. Firstly, compared with HC, abnormally increased ReHo was observed in bilateral sensorimotor regions in new onset BECTS which normalized or even reversed in the chronic BECTS group. Secondly, enhanced ReHo was found in the left frontal language region in the two BECTS groups, with even higher ReHo value in the chronic group. Lastly, decreased ReHo was found in regions of the default mode network (DMN), bilateral occipital lobes and cerebellum in both the new onset and chronic BECTS groups, lower in chronic BECTS. Behavioral analyses of school scores showed the chronic BECTS group presented significantly lower scores compared to HC (p<.05).The coherence of low frequency fluctuations is disrupted in sensorimotor, language and DMN-related regions in new-onset BECTS. Some of these effects seem to be selectively normalized in chronic BECTS, thus allowing us to explore possible chronicity and AED-induced effects on BECTS. Abnormal ReHo in left language and DMN regions could be responsible for impairments of cognitive function.
View details for DOI 10.1016/j.eplepsyres.2015.06.017
View details for Web of Science ID 000361575600010
View details for PubMedID 26354170
Delay Period Activity of the Substantia Nigra during Proactive Control of Response Selection as Determined by a Novel fMRI Localization Method
JOURNAL OF COGNITIVE NEUROSCIENCE
2015; 27 (6): 1238-1248
The ability to proactively control motor responses, particularly to overcome overlearned or automatic actions, is an essential prerequisite for adaptive, goal-oriented behavior. The substantia nigra (SN), an element of the BG, has figured prominently in current models of response selection. However, because of its small size and proximity to functionally distinct subcortical structures, it has been challenging to test the SN's involvement in response selection using conventional in vivo functional neuroimaging approaches. We developed a new fMRI localization method for directly distinguishing, on echo-planar images, the SN BOLD signal from that of neighboring structures, including the subthalamic nucleus (STN). Using this method, we tested the hypothesis that the SN supports the proactive control of response selection. We acquired high-resolution EPI volumes at 3 T from 16 healthy participants while they completed the Preparing to Overcome Prepotency task of proactive control. There was significantly elevated delay period signal selectively during high- compared with low-control trials in the SN. The STN did not show delay period activity in either condition. SN delay period signal was significantly inversely associated with task performance RTs across participants. These results suggest that our method offers a novel means for measuring SN BOLD responses, provides unique evidence of SN involvement in cognitive control in humans, and suggests a novel mechanism for proactive response selection.
View details for DOI 10.1162/jocn_a_00775
View details for Web of Science ID 000354111600014
View details for PubMedID 25514657
Functional connectivity changes in the language network during stroke recovery.
Annals of clinical and translational neurology
2015; 2 (2): 185-195
Several neuroimaging studies have examined language reorganization in stroke patients with aphasia. However, few studies have examined language reorganization in stroke patients without aphasia. Here, we investigated functional connectivity (FC) changes after stroke in the language network using resting-state fMRI and performance on a verbal fluency (VF) task in patients without clinically documented language deficits.Early-stage ischemic stroke patients (N = 26) (average 5 days from onset), 14 of whom were tested at a later stage (average 4.5 months from onset), 26 age-matched healthy control subjects (HCs), and 12 patients with cerebrovascular risk factors (patients at risk, PR) participated in this study. We examined FC of the language network with 23 seed regions based on a previous study. We evaluated patients' behavioral performance on a VF task and correlation between brain resting-state FC (rsFC) and behavior.Compared to HCs, early stroke patients showed significantly decreased rsFC in the language network but no difference with respect to PR. Early stroke patients showed significant differences in performance on the VF task compared to HCs but not PR. Late-stage patients compared to HCs and PR showed no differences in brain rsFC in the language network and significantly stronger connections compared to early-stage patients. Behavioral differences persisted in the late stage compared to HCs. Change in specific connection strengths correlated with changes in behavior from early to late stage.These results show decreased rsFC in the language network and verbal fluency deficits in early stroke patients without clinically documented language deficits.
View details for DOI 10.1002/acn3.165
View details for PubMedID 25750922
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