Kun Hu - Academia.edu (original) (raw)

Papers by Kun Hu

Annals of Neurology, 2015

The suprachiasmatic nucleus (SCN) of the hypothalamus, the master mammalian circadian pacemaker, ... more The suprachiasmatic nucleus (SCN) of the hypothalamus, the master mammalian circadian pacemaker, synchronizes endogenous rhythms with the external day-night cycle. Older humans, particularly those with Alzheimer's disease (AD), often have difficulty maintaining normal circadian rhythms compared to younger adults, but the basis of this change is unknown. We report that the circadian rhythm amplitude of motor activity in both AD subjects and age-matched controls is correlated with the number of vasoactive intestinal peptide-expressing SCN neurons. AD was additionally associated with delayed circadian phase compared to cognitively healthy subjects, suggesting distinct pathologies and strategies for treating aging-and AD-related circadian disturbances.

Sleep

Study Objectives: Healthy physiology is characterized by fractal regulation (FR) that generates s... more Study Objectives: Healthy physiology is characterized by fractal regulation (FR) that generates similar structures in the fluctuations of physiological outputs at different time scales. Perturbed FR is associated with aging and age-related pathological conditions. Shift work, involving repeated and chronic exposure to misaligned environmental and behavioral cycles, disrupts circadian coordination. We tested whether night shifts perturb FR in motor activity and whether night shifts affect FR in chronic shift workers and non-shift workers differently. Methods: We studied 13 chronic shift workers and 14 non-shift workers as controls using both field and in-laboratory experiments. In the in-laboratory study, simulated night shifts were used to induce a misalignment between the endogenous circadian pacemaker and the sleep-wake cycles (ie, circadian misalignment) while environmental conditions and food intake were controlled. Results: In the field study, we found that FR was robust in controls but broke down in shift workers during night shifts, leading to more random activity fluctuations as observed in patients with dementia. The night shift effect was present even 2 days after ending night shifts. The in-laboratory study confirmed that night shifts perturbed FR in chronic shift workers and showed that FR in controls was more resilience to the circadian misalignment. Moreover, FR during real and simulated night shifts was more perturbed in those who started shift work at older ages. Conclusions: Chronic shift work causes night shift intolerance, which is probably linked to the degraded plasticity of the circadian control system.

JSM biomarkers, 2017

Motor activity in humans and other animals possesses fractal temporal fluctuations that co-exists... more Motor activity in humans and other animals possesses fractal temporal fluctuations that co-exists with circadian or daily activity rhythms. The perturbations in fractal activity patterns are often accompanied by altered circadian/daily rhythms. The goal of this study is to test whether fractal regulation in motor activity provides physiological information independent from 24-h/circadian rhythmicity. To achieve the goal, we studied locomotor activity recordings of rats with the lesion of the suprachiasmatic nucleus (SCN) that are known to have diminished circadian/daily activity rhythms and perturbed fractal regulation. By restricting feeding time (i.e., food was only availability in the dark period of the 12h: 12h light-dark cycles), we found that mean activity levels in these animals displayed significant 24-h rhythms. In contrast, the restricted feeding had no influences on the perturbed fractal regulation in these SCN-lesioned animals, i.e., activity fluctuations in these animal...

Journal of Biological Rhythms, 2017

Shift work is a risk factor for inflammation, hypertension and cardiovascular disease. This incre... more Shift work is a risk factor for inflammation, hypertension and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. Shift workers' behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in shift workers, independent of differences in work stress, food quality and other factors that are likely to differ between night and day shifts. Thus, our objectives were to determine the independent effect of circadian misalignment on 24-h high-sensitivity C-reactive protein (hs-CRP; a marker of systemic inflammation) and blood pressure levels-cardiovascular disease risk factors-in chronic shift workers. Chronic shift workers undertook two 3-day laboratory protocols that simulated night work comprised of 12-hour inverted behavioral and environmental cycles (circadian misalignment) or simulated day work (circadian alignment), using a randomized, crossover design. Circadian misalignment increased 24-h hs-CRP by 11% (P<0.0001). Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 1.4 mmHg and 0.8 mmHg, respectively (both P≤0.038). The misalignment-mediated increase in 24-h SBP was primarily explained by an increase in SBP during the wake period (+1.7 mmHg; P=0.017), whereas the misalignment-mediated increase in 24-h DBP was primarily explained by an increase in DBP during the sleep opportunity (+1.8 mmHg; P=0.005). Circadian misalignment per se increases hs-CRP and blood pressure in shift workers. This may help explain the increased inflammation, hypertension and cardiovascular disease risk in shift workers.

Physica A, Jan 15, 2016

Recent studies of brain activities show that cross-frequency coupling (CFC) play an important rol... more Recent studies of brain activities show that cross-frequency coupling (CFC) play an important role in memory and learning. Many measures have been proposed to investigate the CFC phenomenon, including the correlation between the amplitude envelopes of two brain waves at different frequencies - cross-frequency amplitude-amplitude coupling (AAC). In this short communication, we describe how nonstationary, nonlinear oscillatory signals may produce spurious cross-frequency AAC. Utilizing the empirical mode decomposition, we also propose a new method for assessment of AAC that can potentially reduce the effects of nonlinearity and nonstatonarity and, thus, help to avoid the detection of artificial AACs. We compare the performances of this new method and the traditional Fourier-based AAC method. We also discuss the strategies to identify potential spurious AACs.

We investigate if known extrinsic and intrinsic factors fully account for the complex features ob... more We investigate if known extrinsic and intrinsic factors fully account for the complex features observed in recordings of human activity as measured from forearm motion in subjects undergoing their regular daily routine. We demonstrate that the apparently random forearm motion possesses previously unrecognized dynamic patterns characterized by fractal and nonlinear dynamics. These patterns are unaffected by changes in the average activity level, and persist when the same subjects undergo time-isolation laboratory experiments designed to account for the circadian phase and to control the known extrinsic factors. We attribute these patterns to a novel intrinsic multi-scale dynamic regulation of human activity.

Scientific reports, Jun 13, 2016

Cross-sectional studies show that activity fluctuations in healthy young adults possess robust te... more Cross-sectional studies show that activity fluctuations in healthy young adults possess robust temporal correlations that become altered with aging, and in dementia and depression. This study was designed to test whether or not within-subject changes of activity correlations (i) track the clinical progression of dementia, (ii) reflect the alterations of depression symptoms in patients with dementia, and (iii) can be manipulated by clinical interventions aimed at stabilizing circadian rhythmicity and improving sleep in dementia, namely timed bright light therapy and melatonin supplementation. We examined 144 patients with dementia (70-96 years old) who were assigned to daily treatment with bright light, bedtime melatonin, both or placebos only in a 3.5-year double-blinded randomized clinical trial. We found that activity correlations at temporal scales <~2 hours significantly decreased over time and that light treatment attenuated the decrease by ~73%. Moreover, the decrease of te...

Aps March Meeting Abstracts, Mar 1, 2004

Findings indicate a dynamical coupling between respiratory and cardiac function. However, the nat... more Findings indicate a dynamical coupling between respiratory and cardiac function. However, the nature of this nonlinear interaction remains not well understood. We investigate transient patterns in the cardio-pulmonary interaction under healthy conditions by means of cross-correlation and nonlinear synchronization techniques, and we compare how these patterns change under pathologic conditions such as obstructive sleep apnea --- a periodic cessation of

Aps Meeting Abstracts, Feb 28, 2004

Numerous epidemiological studies demonstrate that sudden cardiac death, pulmonary embolism, myoca... more Numerous epidemiological studies demonstrate that sudden cardiac death, pulmonary embolism, myocardial infarction, and stroke have a 24-hour daily pattern with a broad peak between 9-11am. Such a daily pattern in cardiovascular risk could be attributable to external factors, such as the daily behavior patterns, including sleep-wake cycles and activity levels, or internal factors, such as the endogenous circadian pacemaker. Findings of significant alternations in the temporal organization and nonlinear properties of heartbeat fluctuations with disease and with sleep-wake transitions raise the intriguing possibility that changes in the mechanism of control associated with behavioral sleep-wake transition may be responsible for the increased cardiac instability observed in particular circadian phases. Alternatively, we hypothesize that there is a circadian clock, independent of the sleep-wake cycle, which affects the cardiac dynamics leading to increased cardiovascular risk. We analyzed continuous recordings from healthy subjects during 7 cycles of forced desynchrony routine wherein subjects' sleep-wake cycles are adjusted to 28 hours so that their behaviors occur across all circadian phases. Heartbeat data were divided into one-hour segments. For each segment, we estimated the correlations and the nonlinear properties of the heartbeat fluctuations at the corresponding circadian phase. Since the sleep and wake contributions are equally weighted in our experiment, a change of the properties of the heartbeat dynamics with circadian phase suggest a circadian rhythm. We show significant circadian-mediated alterations in the correlation and nonlinear properties of the heartbeat resembling those observed in patients with heart failure. Remarkably, these dynamical alterations are centered at 60 degrees circadian phase, coinciding with the 9-11am window of cardiac risk.

Fluctuations and Noise in Biological Biophysical and Biomedical Systems, 2003

ABSTRACT

Frontiers in physiology, 2016

One evolutionary adaptation in motor activity control of animals is the anticipation of food that... more One evolutionary adaptation in motor activity control of animals is the anticipation of food that drives foraging under natural conditions and is mimicked in laboratory with daily scheduled food availability. Food anticipation is characterized by increased activity a few hours before the feeding period. Here we report that 2-h food availability during the normal inactive phase of rats not only increases activity levels before the feeding period but also alters the temporal organization of motor activity fluctuations over a wide range of time scales from minutes up to 24 h. We demonstrate this multiscale alteration by assessing fractal patterns in motor activity fluctuations-similar fluctuation structure at different time scales-that are robust in intact animals with ad libitum food access but are disrupted under food restriction. In addition, we show that fractal activity patterns in rats with ad libitum food access are also perturbed by lesion of the dorsomedial hypothalamic (DMH)-...

Proceedings of the National Academy of Sciences of the United States of America, Jan 8, 2016

Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This incr... more Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show-by using two 8-d laboratory protocols-that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure dur...

Journal of biological rhythms, Jan 29, 2016

The role of specific cortical regions in sleep-regulating circuits is unclear. The anterior insul... more The role of specific cortical regions in sleep-regulating circuits is unclear. The anterior insula (AI) has strong reciprocal connectivity with wake and sleep-promoting hypothalamic and brainstem regions, and we hypothesized that the AI regulates patterns of sleep and wakefulness. To test this hypothesis, we lesioned the AI in rats (n = 8) and compared sleep, wake, and activity regulation in these animals with nonlesioned controls (n = 8) with 24-h sleep recordings and chronic infrared activity monitoring. Compared to controls, animals with AI lesions had decreased wakefulness and increased rapid eye movement (REM) sleep and non-REM (NREM) sleep. AI-lesioned animals had shorter wake bouts, especially during the active dark phase. AI-lesioned animals also had more transitions from NREM to REM sleep, especially during the inactive light phase. Chronic infrared monitoring revealed that AI-lesioned animals also had a disturbed temporal organization of locomotor activity at multiple time...

International Journal of Gerontology, 2013

The purpose of this study was to examine effects of mixed interval aerobic and strength training ... more The purpose of this study was to examine effects of mixed interval aerobic and strength training (MAST) program on physiological functions in older women with metabolic syndrome. 12 subjects were randomly assigned to the exercise group (16-week MAST program) or the control group. Outcomes included oxygen uptake (VO 2max ), cerebral blood flow velocity (BFV) and cognitive functions. The exercise group demonstrated increased VO 2max and certain improvements in cognitive functions. No changes were observed in BFV for both groups. These results can be used as a preliminary data for planning larger studies.

Philosophical transactions. Series A, Mathematical, physical, and engineering sciences, Jan 13, 2016

The Holo-Hilbert spectral analysis (HHSA) method is introduced to cure the deficiencies of tradit... more The Holo-Hilbert spectral analysis (HHSA) method is introduced to cure the deficiencies of traditional spectral analysis and to give a full informational representation of nonlinear and non-stationary data. It uses a nested empirical mode decomposition and Hilbert-Huang transform (HHT) approach to identify intrinsic amplitude and frequency modulations often present in nonlinear systems. Comparisons are first made with traditional spectrum analysis, which usually achieved its results through convolutional integral transforms based on additive expansions of an a priori determined basis, mostly under linear and stationary assumptions. Thus, for non-stationary processes, the best one could do historically was to use the time-frequency representations, in which the amplitude (or energy density) variation is still represented in terms of time. For nonlinear processes, the data can have both amplitude and frequency modulations (intra-mode and inter-mode) generated by two different mechanis...

Gait & Posture, 2015

The pendulum test is a standard clinical test for quantifying the severity of spasticity. In the ... more The pendulum test is a standard clinical test for quantifying the severity of spasticity. In the test, an electrogoniometer is typically used to measure the knee angular motion. The device is costly and difficult to set up such that the pendulum test is normally time consuming. The goal of this study is to determine whether a Nintendo Wii remote can replace the electrogroniometer for reliable assessment of the angular motion of the knee in the pendulum test. The pendulum test was performed in three control participants and 13 hemiplegic stroke patients using both a Wii remote and an electrogoniometer. The correlation coefficient and the Bland-Altman difference plot were used to compare the results obtained from the two devices. The Wilcoxon signed-rank test was used to compare the difference between hemiplegia-affected and nonaffected sides in the hemiplegic stroke patients. There was a fair to strong correlation between measurements from the Wii remote and the electrogoniometer (0.513&amp;amp;amp;amp;amp;lt;R(2)&amp;amp;amp;amp;amp;lt;0.800). Small but consistent differences between the Wii remote and electrogoniometer were identified from the Bland-Altman difference plot. Within the hemiplegic stroke patients, both devices successfully distinguished the hemiplegia-affected (spastic) side from the nonaffected (nonspastic) side (both with p&amp;amp;amp;amp;amp;lt;.0001*). In addition, the intraclass correlation coefficient, standard error of measurement, and minimum detectable differences were highly consistent for both devices. Our findings suggest that the Wii remote may serve as a convenient and cost-efficient tool for the assessment of spasticity.

Neuroscience Letters, 2015

In order to maintain stable upright stance, the postural control system must account for the cont... more In order to maintain stable upright stance, the postural control system must account for the continuous perturbations to the body&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s center-of-mass including those caused by spontaneous respiration. Both aging and disease increase &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;posturo-respiratory synchronization;&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; which reflects the degree to which respiration affects postural sway fluctuations over time. Tai Chi training emphasizes the coordination of respiration and bodily movements and may therefore optimize the functional interaction between these two systems. The purpose of the project was to examine the effect of Tai Chi training on the interaction between respiration and postural control in older adults. We hypothesized that Tai Chi training would improve the ability of the postural control system to compensate for respiratory perturbations and thus, reduce posturo-respiratory synchronization. Participants were recruited from supportive housing facilities and randomized to a 12-week Tai Chi intervention (n=28; 86±5yrs) or educational-control program (n=34, 85±6yrs). Standing postural sway and respiration were simultaneously recorded with a force plate and respiratory belt under eyes-open and eyes-closed conditions. Posturo-respiratory synchronization was determined by quantifying the variation of the phase relationship between the dominant oscillatory mode of respiration and corresponding oscillations within postural sway. Groups were similar in age, gender distribution, height, body mass, and intervention compliance. Neither intervention altered average sway speed, sway magnitude or respiratory rate. As compared to the education-control group, however, Tai Chi training reduced posturo-respiratory synchronization when standing with eyes open or closed (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Tai Chi training did not affect traditional parameters of standing postural control or respiration, yet reduced the coupling between respiration and postural control. The beneficial effects of Tai Chi training may therefore stem in part from optimization of this multi-system interaction.