J. Jean Chen's research while affiliated with University of Toronto and other places

Publications (73)

Article
Background: Neurological symptoms associated with coronavirus disease 2019 (COVID-19), such as fatigue and smell/taste changes, persist beyond infection. However, little is known of brain physiology in the post-COVID-19 timeframe. Purpose: To determine whether adults who experienced flu-like symptoms due to COVID-19 would exhibit cerebral blood...
Article
Full-text available
Conventionally, cerebrovascular reactivity (CVR) is estimated as the amplitude of the hemodynamic response to vascular stimuli, most commonly carbon dioxide (CO2). While the CVR amplitude has established clinical utility, the temporal characteristics of CVR (dCVR) have been increasingly explored and may yield even more pathology-sensitive parameter...
Preprint
Full-text available
There has been growing attention on the effect of COVID-19 on white-matter microstructure, especially among those that self-isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single-shell diffusion MRI methods for detecting such effects. In this work, the sensitivit...
Preprint
Full-text available
The role of vascular risk factors in age-related brain degeneration has long been the subject of intense study. As its own sub-category of vascular risk, obesity has an increasingly recognized role in influencing brain health and health-care strategies, but its association with brain health remains under-studied. Notably, no prior study has address...
Preprint
In the context of fMRI, carbon dioxide (CO2) is a well-known vasodilator that has been widely used to monitor and interrogate vascular physiology. Moreover, spontaneous fluctuations in end-tidal carbon dioxide (PETCO2) reflects changes in arterial CO2 and has been demonstrated as the largest physiological noise source in the low-frequency range of...
Preprint
Full-text available
Conventionally, cerebrovascular reactivity (CVR) is estimated as the amplitude of the hemodynamic response to vascular stimuli. While the CVR amplitude has established clinical utility, the temporal characteristics of CVR have been increasingly explored and may yield even more pathology-sensitive parameters. This work is motivated by the current ne...
Article
Changes in levels of the inhibitory neurotransmitter γ‐aminobutyric acid (GABA) may underlie aging‐related changes in brain function. GABA and co‐edited macromolecules (GABA+) can be measured with MEGA‐PRESS magnetic resonance spectroscopy (MRS). The current study investigated how changes in the aging brain impact the interpretation of GABA+ measur...
Article
Full-text available
Effective separation of signal from noise (including physiological processes and head motion) is one of the chief challenges for improving the sensitivity and specificity of resting-state fMRI (rs-fMRI) measurements and has a profound impact when these noise sources vary between populations. Independent component analysis (ICA) is an approach for a...
Preprint
Full-text available
The long-term consequences of coronavirus disease 2019 (COVID-19) on brain physiology and function are not yet well understood. From the recently described NeuroCOVID-19 study, we examined cerebral blood flow (CBF) in 50 participants recruited to one of two groups: 1) adults who previously self-isolated at home due to COVID-19 (n = 39; 116.5 ± 62.2...
Article
Conventional functional MRI (fMRI) with blood-oxygenation level dependent (BOLD) contrast is an important tool for mapping human brain activity non-invasively. Recent interest in quantitative fMRI has renewed the importance of oxidative neuroenergetics as reflected by cerebral metabolic rate of oxygen consumption (CMR O2 ) to support brain function...
Article
Full-text available
Resting-state functional magnetic resonance imaging (rs-fMRI) has been extensively used to study brain aging, but the age effect on the frequency content of the rs-fMRI signal has scarcely been examined. Moreover, the neuronal implications of such age effects and age-sex interaction remain unclear. In this study, we examined the effects of age and...
Article
Studies of healthy brain aging have reported diffusivity patterns associated with white matter degeneration using diffusion tensor imaging (DTI), which assumes that diffusion measured at typical b-values (approximately 1000 s/mm²) is Gaussian. Diffusion kurtosis imaging (DKI) is an extension of DTI that measures non-Gaussian diffusion (kurtosis) to...
Chapter
Functional MRI (fMRI) is primarily based on the same blood oxygenation level-dependent (BOLD) phenomenon that MRI-based cerebrovascular reactivity (CVR) mapping has relied upon. This technique is finding an ever-increasing role in neuroscience and clinical research as well as treatment planning. The estimation of CVR has unique applications in and...
Preprint
Full-text available
Studies of healthy brain aging have reported diffusivity patterns associated with white matter degeneration using diffusion tensor imaging (DTI), which assumes that diffusion measured at the typical b-value (approximately 1000 s/mm2) is Gaussian. Diffusion kurtosis imaging (DKI) is an extension of DTI that measures non-Gaussian diffusion (kurtosis)...
Article
Full-text available
Background: The detailed extent of neuroinvasion or deleterious brain changes resulting from COVID-19 and their time courses remain to be determined in relation to "long-haul" COVID-19 symptoms. Our objective is to determine whether there are alterations in functional brain imaging measures among people with COVID-19 after hospital discharge or se...
Preprint
Full-text available
Effective separation of signal from noise (including physiological processes and head motion) is one of the chief challenges for improving the sensitivity and specificity of resting-state fMRI (rs-fMRI) measurements and has a profound impact when these noise sources vary between populations. Independent component analysis (ICA) is an approach for a...
Article
Heart rate variability (HRV) is a well-established surrogate of cardiac and emotional health that reflects the balance between sympathetic and parasympathetic activity of the autonomic nervous system. We examined the impact of manipulating exhalation to inhalation ratio (E:I) on HRV, without altering the intrinsic breathing rate of healthy individu...
Article
Background: Subjective cognitive decline (SCD) is associated with increased risk of developing Alzheimer's disease (AD). However, the underlying mechanisms for this association remain unclear. Neuroimaging studies suggest the earliest AD-related changes are large-scale network disruptions, beginning in the posterior default mode (pDMN) network. O...
Article
Full-text available
Task and resting-state functional MRI (fMRI) is primarily based on the same blood-oxygenation level-dependent (BOLD) phenomenon that MRI-based cerebrovascular reactivity (CVR) mapping has most commonly relied upon. This technique is finding an ever-increasing role in neuroscience and clinical research as well as treatment planning. The estimation o...
Article
Full-text available
In vivo mapping of cerebrovascular oscillations in the 0.05-0.15 Hz remains difficult. Oscillations in the cerebrospinal fluid (CSF) represent a possible avenue for noninvasively tracking these oscillations using resting-state functional MRI (rs-fMRI), and have been used to correct for vascular oscillations in rs-fMRI functional connectivity. Howev...
Article
Diffusion tensor imaging (DTI) consistently detects increased mean diffusivity (MD) and decreased fractional anisotropy (FA) with advancing age in regions of primarily single white matter (WM) fibre populations, but findings have been inconsistent in regions of more complex fibre architecture. Given that DTI remains more common for characterizing a...
Article
Full-text available
The desire to enhance the sensitivity and specificity of resting-state (rs-fMRI) measures has prompted substantial recent research into removing noise components. Chief among contributions to noise in rs-fMRI are physiological processes, and the neuronal implications of respiratory-volume variability (RVT), a main rs-fMRI-relevant physiological pro...
Article
Full-text available
Damage to the fornix leads to significant memory impairment and executive dysfunction and is associated with dementia risk. We sought to identify if fornix integrity and fiber length are disrupted in mild cognitive impairment (MCI) and how they associate with cognition. Data from 14 healthy older adult controls (HCs) and 17 subjects with non-amnest...
Preprint
Full-text available
Frequency and amplitude features of both resting-state electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are crucial metrics that reveal patterns of brain health in aging. However, the association between these two modalities is still unclear. In this study, we examined the peak frequency and standard deviation of both m...
Preprint
Slow and rhythmic spontaneous oscillations of cerebral blood flow are well known to have diagnostic utility, notably frequencies of 0.008-0.03 Hz (B-waves) and 0.05-0.15Hz (Mayer waves or M waves). However, intracranial measurements of these oscillations have been difficult. Oscillations in the cerebrospinal fluid (CSF), which are influenced by the...
Preprint
Full-text available
The desire to enhance the sensitivity and specificity of resting-state (rs-fMRI) measures has prompted substantial recent research into removing noise components. Chief among contributions to noise in rs-fMRI are physiological processes, and the neuronal implications of respiratory-volume variability (RVT), a main rs-fMRI-relevant physiological pro...
Article
Full-text available
γ-aminobutyric acid (GABA), primary inhibitory neurotransmitter in the brain, plays a significant role in aging and in neurodegenerative disorders, including Alzheimer’s disease (AD). We investigated the relationship between GABA levels in the dorsomedial/dorsoanterolateral prefrontal cortex (DM/DA-PFC) and memory in high-AD risk participants. Thir...
Article
Full-text available
The BOLD signal, as the basis of functional MRI, arises from both neuronal and vascular factors, with their respective contributions to resting state-fMRI still unknown. Among the factors contributing to “physiological noise”, dynamic arterial CO2 fluctuations constitutes the strongest and the most widespread modulator of the grey-matter rs-fMRI si...
Preprint
Full-text available
The BOLD signal, as the basis of functional MRI, arises from both neuronal and vascular factors, with their respective contributions to resting state-fMRI still unknown. Among the factors contributing to 'physiological noise', dynamic arterial CO2 fluctuations constitutes the strongest and the most widespread modulator of the grey-matter rs-fMRI si...
Article
Full-text available
Resting‐state functional magnetic resonance imaging (rs‐fMRI) is frequently used to study brain function; but, it is unclear whether BOLD‐signal fluctuation amplitude and functional connectivity are associated with vascular factors, and how vascular‐health factors are reflected in rs‐fMRI metrics in the healthy population. As arterial stiffening is...
Preprint
Full-text available
Synopsis In this study, the relationship between EEG alpha band power and the BOLD signal is examined in the thalamus. We overcome previous limitations in temporal resolution by using fast fMRI (MREG) acquisitions. We also consider a wider range of lags between EEG and BOLD signals than previous studies. In addition, cross correlations between alph...
Article
Full-text available
The frequency characteristics of the resting-state BOLD fMRI (rs-fMRI) signal are of increasing scientific interest, as we discover more frequency-specific biological interpretations. In this work, we use variational mode decomposition (VMD) to precisely decompose the rs-fMRI time series into its intrinsic mode functions (IMFs) in a data-driven man...
Article
In this work, we characterize contrast origins and noise contributions of spin echo (SE) EPI BOLD signal at 3 T. SE BOLD is a fMRI method of choice for imaging brain regions affected by susceptibility artifacts at lower fields, but its sensitivity remains a limiting factor for whole-brain imaging. To resolve this, the signal and noise contributions...
Article
Diffusion tensor imaging (DTI) has been used extensively to investigate white matter (WM) microstructural changes during healthy adult aging. However, WM fibers are known to shrink throughout the lifespan, leading to larger interstitial spaces with age. This could allow more extracellular free water molecules to bias DTI metrics, which are relied u...
Article
Neuroplasticity accompanying learning is a key mediator of stroke rehabilitation. Training in playing music in healthy populations and patients with movement disorders requires resources within motor, sensory, cognitive, and affective systems, and coordination among these systems. We investigated effects of music-supported therapy (MST) in chronic...
Article
Full-text available
Biomarkers that represent the structural and functional integrity of the motor system enable us to better assess motor outcome post-stroke. The degree of overlap between the stroke lesion and corticospinal tract (CST Injury) is a measure of the structural integrity of the motor system, whereas the left-to-right motor cortex resting state connectivi...
Article
Full-text available
Brain aging and associated neurodegeneration constitute a major societal challenge as well as one for the neuroimaging community. A full understanding of the physiological mechanisms underlying neurodegeneration still eludes medical researchers, fuelling the development of in vivo neuroimaging markers. Hence it is increasingly recognized that our u...
Article
The measurement of cerebral blood volume (CBV) has been the topic of numerous neuroimaging studies. To date, however, most in vivo imaging approaches can only measure CBV summed over all types of blood vessels, including arterial, capillary and venous vessels in the microvasculature (i.e. total CBV or CBVtot). As different types of blood vessels ha...
Article
The blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal is commonly used to assess functional connectivity across brain regions, particularly in the resting state (rs-fMRI). However, the BOLD fMRI signal is not merely a representation of neural activity, but a combination of neural activity and vascular resp...
Article
Previous studies have found that aperiodic, systemic low-frequency oscillations (sLFOs) are present in blood-oxygen-level-dependent (BOLD) data. These signals are in the same low frequency band as the “resting state” signal; however, they are distinct signals which represent non-neuronal, physiological oscillations. The same sLFOs are found in the...
Article
Simultaneous multi-slice echo-planar imaging (EPI) can enhance the spatiotemporal resolution of resting-state functional MRI (rs-fMRI) by encoding and simultaneously imaging "groups" of slices. However, phenomena including respiration, cardiac pulsatility, respiration volume per time (RVT) and cardiac-rate variation (CRV), referred to as "physiolog...
Article
Movement is traditionally viewed as a process that involves motor brain regions. However, movement also implicates non-motor regions such as prefrontal and parietal cortex, regions whose integrity may thus be important for motor recovery after stroke. Importantly, focal brain damage can affect neural functioning within and between distinct brain ne...
Article
Full-text available
The resting-state fMRI (rs-fMRI) signal is affected by a variety of low-frequency physiological phenomena, including variations in cardiac-rate (CRV), respiratory-volume (RVT) and end-tidal CO2 (PETCO2). While these effects have become better understood in recent years, the impact that their correction has on the quality of rs-fMRI measurements has...
Article
Prospective motion correction is a promising candidate solution to suppress the effects of head motion during fMRI, ideally allowing the imaging plane to remain fixed with respect to the moving head. Residual signal artifacts may remain, however, because head motion in relation to a fixed multi-channel receiver coil (with non-uniform sensitivity ma...
Article
Full-text available
Echo planar imaging (EPI) suffers from geometric distortions caused by magnetic field inhomogeneities, which can be time-varying as a result of small amounts of head motion that occur over seconds and minutes during fMRI experiments, also known as “dynamic geometric distortion”. Phase Labeling for Additional Coordinate Encoding (PLACE) is a promisi...
Article
Gradient-echo (GE) echo-planar imaging (EPI) is the method of choice in blood-oxygenation level dependent (BOLD) functional MRI (fMRI) studies, as it demonstrates substantially higher BOLD sensitivity than its spin-echo (SE) counterpart. However, it is also well known that the GE-EPI signal is prone to signal dropouts and shifts due to susceptibili...
Article
The objective of this study was to determine whether physiological fluctuations in white matter (PFWM) on resting-state functional magnetic resonance images could be used as an index of neurodegeneration and Alzheimer's disease (AD). Using resting-state functional magnetic resonance image data from participants in the Alzheimer's Disease Neuroimagi...
Data
Full-text available
The blood oxygenation level-dependent (BOLD) phenomenon has profoundly revolutionized neuroscience, with applications ranging from normal brain development and aging, to brain disorders and diseases. While the BOLD effect represents an invaluable tool to map brain function, it does not measure neural activity directly; rather, it reflects changes i...
Article
Arterial-spin labelling (ASL) is an increasingly established magnetic resonance imaging (MRI) technique that is finding broader applications in studying the healthy and diseased brain. This review addresses the use of ASL to assess brain function in the resting state. Following a brief technical description, we discuss the use of ASL in the followi...
Article
The blood oxygenation level-dependent (BOLD) phenomenon has profoundly revolutionized neuroscience, with applications ranging from normal brain development and aging, to brain disorders and diseases. While the BOLD effect represents an invaluable tool to map brain function, it does not measure neural activity directly; rather, it reflects changes i...
Article
There has been tremendous interest in applying fMRI-based resting-state functional connectivity (fcMRI) measurements to the study of brain function. However, a lack of understanding of the physiological mechanisms of fcMRI limits our ability to interpret fcMRI findings. In this work, we examine regional associations between fcMRI estimates and dyna...
Conference Paper
Full-text available
Background / Purpose: There has been great interest in applying resting-state functional connectivity using fMRI (fcMRI) to the study of brain function. However, a lack of understanding of the physiological mechanisms of fcMRI limits our ability to interpret fcMRI findings. In this work, we examine regional associations of fcMRI estimates with (i...
Article
Age-associated white matter degeneration has been well documented and is likely an important mechanism contributing to cognitive decline in older adults. Recent work has explored a range of noninvasive neuroimaging procedures to differentially highlight alterations in the tissue microenvironment. Diffusional kurtosis imaging (DKI) is an extension o...
Data
Correlation matrix for DTI-derived white-matter microstructural parameters. There was no clear correlation trends between FA, AD and RD in the various white-matter ROIs. RD is strongly and negatively correlated with FA across these ROIs. (TIFF)
Data
Associations between cortical CBF and DTI parameters of white-matter integrity, controlled for age (left), contrasted with the results of a multivariate analysis in which each DTI parameter is also modeled as a function of the remaining DTI parameters (right). The latter method results in a much weakened association between the modeled parameter an...
Data
The relationship between age and cortical CBF in the studied cohort (N = 105). The lateral (top) and medial (bottom) surfaces are shown for the left (L) and right (R) cortical surface. Blue indicates a negative correlation, namely, CBF becomes lower with increasing age. In order to minimize partial-volume confound, this relationship has been contro...
Article
Full-text available
Degeneration of cerebral white matter is commonly observed in aging, and the associated degradation in neural connectivity contributes to cognitive decline in older adults. Vascular dysfunction has been implicated as a potential mechanism for general age-related neural tissue deterioration; however, no prior study has examined the direct relationsh...
Article
Alterations in cerebral blood flow (CBF) may play an important role in the pathophysiology of neurodegenerative disorders such as Huntington's disease (HD). While a few reports have suggested reductions in CBF in HD, little is known about their extent and whether, or how, they might be related to atrophy and to clinical symptoms. We used pulsed art...
Article
Prior studies have demonstrated decreasing cerebral blood flow (CBF) in normal aging, but the full spatial pattern and potential mechanism of changes in CBF remain to be elucidated. Specifically, existing data have not been entirely consistent regarding the spatial distribution of such changes, potentially a result of neglecting the effect of age-r...
Article
It is widely assumed in fMRI that the relationship between cerebral blood flow (CBF) and volume (CBV) changes observed during end-tidal CO(2) (PETCO(2)) perturbations is equivalent to that elicited by neuronal activation. This assumption has been validated in PET studies insofar as relating total flow to total CBV changes, but remains unconfirmed f...
Article
The effect of carbon dioxide (CO(2)) on cerebral metabolism is of tremendous interest to functional imaging. In particular, mild-to-moderate hypercapnia is routinely used in calibrated blood oxygen-level dependent (BOLD)-functional magnetic resonance imaging (fMRI)-based quantification of cerebral oxidative metabolism changes (DeltaCMRO(2)), and re...
Article
To understand and predict the blood-oxygenation level-dependent (BOLD) fMRI signal, an accurate knowledge of the relationship between cerebral blood flow (DeltaCBF) and volume (DeltaCBV) changes is critical. Currently, this relationship is widely assumed to be characterized by Grubb's power-law, derived from primate data, where the power coefficien...

Citations

... Machine learning may also be a promising tool to address challenges with reference signal quality. For example, Agrawal et al., 2022 successfully used the respiratory waveform in resting-state data to predict CO2 and derive PETCO2 using a fully convolutional neural network (Agrawal et al., 2022). However, their method does not maintain PETCO2 in quantitative units of mmHg either, which would be preferred for modeling CVR amplitude. ...
... The difference between the two is therefore at the higher order coefficients that contain richer microstructural information ( Özarslan et al., 2013 ). Although DKI has been shown to enhance the sensitivity to age-related patterns in WM compared with DTI ( Coutu et al., 2014 ), kurtosis indices follow the same age associations as the DTI-derived diffusivities ( Beck et al., 2021;Pines et al., 2020;Taha et al., 2022 ), implying that these parameters carry similar information. A key finding of our current study is that MAP-derived NG does not reduce but rather increases with age in most WM ROIs, exhibiting an opposing trend with respect to DKI maps. ...
... Given the sustained requests for EEG services despite restrictions on its performance, including EMU referrals, efforts were made to improve processes and utilize technological advancements to better apply EEG technology to patient care while considering these limitations. New best practice protocols for performing EEG were proposed, including but not limited to disinfection and maintenance of equipment, proper personal protective equipment (PPE) use by patients and staff, the designation of machines to be used in ICU and COVID-19 units, and technologist staffing and safety (8,9,21,26,32,33,(36)(37)(38)(39)(40)(41)(42)(43)(44) . Tertiary care facilities and especially those designated as epilepsy centers with EMUs were forced to create more streamlined and standardized triage protocols for intra-hospital and inter-hospital transfers and coordinating care with outlying hospitals, including teleconsultations (26), leading to safer practices and quicker reinstitution of services (45). ...
... These benefits are varied and include allowing a practitioner to face a threat with lower arousal, 97 make difficult decisions in a short time space, 91 and shift the autonomic nervous system tow a rd parasympathetic dominance. 97 All published studies mention the production of a specific sound during exhalation: a female humming bee (2 studies, 11.8%); a humming bee (5 studies, 29.4%), a bumble bee (3 studies, 17.7%), "OM" (3 studies, 17.7%), "Mmm" (3 studies, 17.7%); and a loud humming sound (1 study, 5.9%). None of the studies mentioned production of any specific sound during inhalation. ...
... For instance, scores from this subjective memory test correlated with prefrontal and default mode network connectivity in our previous study [50]. In older, non-cancer adults with subjective cognitive decline, perceived memory complaints were associated with decreased connectivity between the posterior cingulate cortex and left parahippocampal gyrus, after controlling for depression and overall cognitive functioning [51]. Salience network hypoconnectivity may be a specific biomarker of elevated subjective executive dysfunction, not memory dysfunction. ...
... There is evidence that the shape and timing of the HRF to a neural event may vary across brain regions (Handwerker, Ollinger, & D'Esposito, 2004), with healthy aging (Issard & Gervain, 2018;West et al., 2019), and under different baseline states (Cohen, Ugurbil, & Kim, 2002;Liu et al., 2004). Blood flow changes can also be evoked by a non-neural vasodilatory stimulus such as carbon dioxide, a phenomenon known as cerebrovascular reactivity (CVR) (Chen & Gauthier, 2021;Liu, De Vis, & Lu, 2019;Pinto, Bright, Bulte, & Figueiredo, 2020;Sleight, Stringer, Marshall, Wardlaw, & Thrippleton, 2021). These responses are also delayed, with regional heterogeneity observed across the healthy brain and altered by disease (Bright, Bulte, Jezzard, & Duyn, 2009;Donahue et al., 2016;Holmes et al., 2020;Leung, Duffin, Fisher, & Kassner, 2016;Moia et al., 2020;Siegel, Snyder, Ramsey, Shulman, & Corbetta, 2016;Sousa, Vilela, & Figueiredo, 2014). ...
... In addition, a transfer of LF waves via the IC arterio-venous capacitive coupling [14] would be rather more sensitive to the systolic AF modulation, since the major role of the capacitive coupling is compensating the systolic arterial water-hammer effect. Further evidence supporting this hypothesis is the poor presence of LF waves in the CSFF series [27]. Clearly, the CSF compartment is only capacitively coupled to AF and VF. ...
... skin conductance; though this relationship may depend on ambient temperature; Bini et al., 1980;Jänig et al., 1980). These physiological changes include respiration-driven changes in scalp EEG and local field potentials Shams et al., 2021;Tu & Zhang, 2022;Zelano et al., 2016). Consistent with these findings, resting-state fMRI studies have observed concomitant fluctuations between global BOLD signals, respiratory variance and one or more of these physiological signals (Gu et al., 2022;Yuan et al., 2013). ...
... Diffusion changes in the fornix may act independently and synergistically with amyloid deposition to affect memory change in aging (Rabin et al., 2019). A recent study of nonamnestic memory impairment suggests fornix diffusion parameters may be correlated with executive function (Srisaikaew et al., 2020). The presence of amyloid and other markers of neurodegeneration are associated with tract specific degeneration, including in the fornix in MCI (Jacquemont et al., 2017). ...
... It has been shown that higher participant age is associated with changes in EEG patterns, such as increasing beta activity and decreased alpha activity [46,47]. In this study the testing group, which included 5 participants and 15 assessed tumor resections, was composed of a 29-year-old senior and 29-and 30-year-old junior neurosurgical residents. ...