Research Laboratories and Divisions

Medical Biodynamics Program (MBP)

Department of Medicine, Brigham and Women's Hospital
Director: Kun Hu, PhD

MBP Group Photo 2016

From left: Brigid Falvey, Chien-Hung Yeh, Kun Hu, Peng Li, Melissa Patxot.


Biological control systems are typically very complex, involving multiple, interacted control nodes that function at different time scales. Outputs from these systems such as motor activity, heart rate, and brain activity often display seemingly “irregular” and “unstable” fluctuations with rich dynamic features (e.g., fractal patterns, phase synchronization and cross-frequency phase-amplitude modulation) that are beyond the understanding of traditional neurobiology. How to assess the underlying control mechanisms based on these fluctuations is a contemporary challenge in the field of biology. Concepts and methods derived from modern statistical physics and nonlinear dynamics appear to be able to provide suitable, promising tools for assessing the integrated behaviors of these complex neurophysiological signals on a system level and from a network point of view. The goal of the Medical Biodynamics Program is to foster such translational research in sleep medicine and to create new data analysis methods, mathematical theories, and mechanistic, experimentally-based models for the study of neurophysiological systems. We are interested in a broad range of neurophysiological systems, from the cardiovascular system, to the circadian system, to the brainstem systems generating sleep, through the cortical systems generating complex cognition (see examples of on-going projects below).

Publications:

Click here for Publications by MBP Faculty and Post-doctoral Fellows via PubMed

Training and Employment Opportunities:

Postdoctoral Fellowship and Research Assistant Opportunity

A Postdoctoral Fellow position and a Research Assistant position are available at Brigham and Women’s Hospital (BWH) Division of Sleep and Circadian Disorders in the field of circadian study. The positions involve human studies and nonlinear dynamic analysis to investigate how the circadian regulation and daily behaviors affect sleep, cardiovascular function and task performance (e.g., cognition, mood, and balance). The qualified candidates will receive training in circadian physiology, human experiment and physiological data analysis under the supervision of Dr. Kun Hu at Medical Biodynamics Program (MBP) at BWH.

Primary responsibility for Research Assistant

  1. Recruiting and scheduling participants
  2. Running experimental study sessions and coordinating research study volunteers
  3. Corresponding with the IRB
  4. Maintaining study documentation, assisting in data downloading, and transferring and backup
  5. Performing certain data analyses such as data format conversion, noise filtering, and basic statistical analysis.

Primary responsibility for Postdoctoral Fellow:

  1. Participating in human study design and protocol design
  2. Overseeing recruitment of subjects and IRB
  3. Running experimental study sessions
  4. Performing data analyses and statistical analysis.
  5. Summarizing/presenting scientific findings

Qualifications

  1. Computer skills including working knowledge of PC and Mac operating systems, basic document processing and presentation software (e.g., Microsoft Word, Excel, and Power Point), and basic data processing software (e.g., Matlab)
  2. High level of motivation; ability to work independently and as part of a team; excellent communication, organization, and attention to detail
For Research Assistant:
  1. A bachelor’s degree in biology, neuroscience, psychology, or related field, as well as a 1-year commitment to the position
  2. At least 6 months of experience working in a research setting, which may include undergraduate research experience
For Postdoctoral Fellow:
  1. MD or PhD with a strong background in human physiology
  2. 2-year commitment to the position
  3. Experience in scientific writing, publications, and presentations

How to apply:

For Training and Employment Opportunities in the Medical Biodynamics Program, contact Kun Hu, PhD.

To apply for the Postdoctoral Fellow position, the following documents should be sent by email to Dr. Kun Hu (khu@bics.bwh.harvard.edu)

  1. Cover letter including motivation
  2. CV including contact information for three references
  3. Although this is not a condition of employment, please indicate whether or not you would be eligible for an NIH training fellowship (US citizen or permanent resident).

Studies:

  • Effects of Lifestyle on Autonomic Control in College Students
  • Neuropathology for disrupted multiscale activity control in Alzheimer's disease
  • The Body Clock Guide to Better Health and Daily Performance  

Faculty

Kun Hu, PhD
Kun Hu, Ph.D.
Director



Affiliated Faculty

Frank Scheer for MBP page 201603
Plamen Ch. Ivanov, Ph.D.
Plamen Ch. Ivanov, Ph.D.
Steven A. Shea, Ph.D.
Steve A. Shea, Ph.D.
Men-Tzung Lo, Ph.D.
Chung Keng Peng, Ph.D.
Norden E. Huang, PhD
Jun Lu, M.D., Ph.D.
Vera Novak, M.D., Ph.D.



Postdoctoral Fellows:


Peng Li MBP page

Peng Li, PhD
Postdoctoral Fellow

Chien-Hung Yeh MBP 2016

Chien-Hung Yeh
Postdoctoral Fellow



Research Staff:

Patxtot MBP 2016

Melissa Patxot

Falvey MBP 2016

Brigid Falvey

Current Research Projects

Multiscale regulatory function of the circadian system in heath and disease
One of the most puzzling phenomena in modern physiology is the existence of fractal patterns in a wide range of physiological systems (i.e., the structure of fluctuations are similar at different time scales). The physiological importance of fractal control is demonstrated in numerous studies and exemplified by reduced fractal cardiac and activity controls with aging and under pathological conditions, and most importantly, by the predictive value of reduced fractal cardiac control for decreased survival. Fractal physiology appears to impart some adaptive advantage, and in this context, the existence of fractal patterns challenges the traditional theory of homeostasis of maintaining physiologic constancy. Despite the clear importance of this fractal phenomenon, to date, no underlying mechanism has been established for fractal control in any neural or physiological system. Our recent studies


Multiscale regulatory function of the circadian system in heath and disease

Schematic representations of fractal structures and fluctuations. The tree-like, spatial fractal (Left Panel) has fractal branching, such that the small-scale structure resembles the large-scale form. A fractal temporal process, such as healthy heart rate (Middle Panel) and activity regulation (Right Panel), may generate fluctuations that are statistically fractal. Adapted from Goldberger AL. Lancet 1996; 347(9011):1312-1314.

indicate that the endogenous circadian system is critically involved in the fractal control of motor activity at multiple time scales. To further understand the underlying mechanisms of fractal control and to apply the concept to diagnosis and prognosis of diseases, we have a number of on-going projects, including the following two:                  

(Project 1)
The goal of this project is to formally assess the physiological significance and theneurobiological basis of the fractal regulatory function of the circadian system. To achieve the goal, we have three specific aims:  i) determining the effects of dementia-related changes in the central circadian system on fractal activity control; ii) determining the effects of disrupted daily behavioral cycles (e.g., shift work) on fractal activity control; and iii) identifying neuronal node(s) in the fractal activity control network and their interactions. This project will provide the neurophysiologic basis for the first model of fractal control. Better understanding of the neuronal circuitry involving in circadian and activity regulation ought to provide useful guidance for improved diagnosis and treatment of circadian-related sleep and behavioral disturbances.

(Project 2) We propose to test whether fractal activity control can predict cognitive decline and the risk for AD in elderly subjects. The specific aims are 1) to determine the longitudinal effects of aging and Alzheimer’s disease (AD) on multiscale activity control; 2) to determine prospectively the ability of multiscale activity control to predict the risk of cognitive decline and AD incidence; 3) to identify neurodegenerations in brain that contribute to disrupted multiscale activity control in older subjects. Achieving these aims will define the temporal profile of the degradation in motor activity control and its relationship with neurodegenerations in the brain during the development of AD.

Network features and cognitive significance of theta-gamma coupling in REM sleep
Rapid eye movement (REM) sleep supports optimal processing of procedural, associative, and emotional memories, but the mechanisms underlying its benefits are not well-understood. Our long-term goal is to determine the neurophysiological mechanisms by which REM sleep enhances cognitive performance on learning and memory tasks, with the objective of illuminating how dysfunctions in REM and cognition may be related to psychiatric illness. Our approach is to study rhythms in brain activity, signatures of information transfer and processing in neural networks which are also reliable markers of cognitive processes.
In this project, we study a pattern arising from the interaction of theta (~4 – 10 Hz) and

Network features and cognitive significance of theta-gamma coupling in REM sleep

PAC in field potential (LFP, top) from mouse parietal cortex. Top-middle: theta-filtered LFP; bottom-middle: low gamma-filtered LFP; bottom: high gamma-filtered LFP. From Scheffzuk C et al. Plos One 2011; 6: p. e28489.

gamma (~40 – 180 Hz) frequency rhythms called phase-amplitude coupling (PAC), which links activity in different regions of the brain. PAC has recently been linked to both learning and memory tasks, and to REM sleep. We hypothesize that REM PAC and the network interactions it represents play important causal roles in the cognitive benefits of REM sleep. To test this hypothesis, we are determining which brain regions are specifically connected by PAC during REM, and how the amount of PAC during REM is related to wakeful learning. We are utilizing electroencephalographic (EEG) data collected from mice, rats, and humans, and two new analytical techniques for the measurement of PAC and PAC networks, one recently developed by our lab. We are using these recordings to examine: 1) how the network of brain regions linked by PAC during REM sleep differs from those characteristic of waking and non-REM sleep in rats; 2) how the amount of PAC occurring during REM changes after rats are exposed to a learning-enriched environment; 3) how the amount of PAC occurring during REM changes in mice over the course of four days of training on the Morris water maze, a task known to increase REM sleep; and 4) how PAC occurring during a nap between training and retest on a category learning task correlates with performance on that task in humans.

Effects of cerebral autoregulation on functional outcomes in the elderly


Effects of cerebral autoregulation on functional outcomes in the elderly

Spontaneous oscillations of blood pressure (BP) and cerebral blood flow velocity (BFV) in (A) a 72-year-old healthy woman and (B) a 62-year-old woman with left MCA stroke during supine baseline (Panels 1 to 3). The components corresponding to dominant oscillations at frequency from ~0.1 to 0.4Hz (Panels 4) were extracted and used for the assessment of BP-BFV relationship. The average BP-BFV phase shifts were large (~60º) in the control subject and small (~10º) in the stroke subject (Panels 5, dash lines).

Cerebral autoregulation (CA) is an important vascular control mechanism that regulates blood supply to brain tissue to match metabolic demands during daily activities. CA involves dilation and constriction of cerebral arterioles in response to changes of systemic blood pressure (BP) through myogenic and neurogenic mechanisms. Impaired CA increases the dependence of cerebral blood flow (CBF) on systemic BP, which may lead to hypoperfusion or hyperperfusion when BP fluctuates, even within the normal pressure range (50-150 mmHg). We and others have shown that CA is impaired in cerebromicrovascular diseases associated with age, hypertension and diabetes, and is even more impaired after stroke. However, it is still unclear whether or how the CA impairment affects neuroanatomical brain structures and, thus, contributes to functional decline in older individuals. The goals of this project are to determine the effects of the CA impairment on brain structure and to test the ability of CA to predict functional outcomes in elderly subjects.


Administrative Contact Name

Ellen Young
eyoung1@partners.org

Medical Biodynamics Program, Division of Sleep Medicine, BWH
221 Longwood Ave
Boston, MA 02115

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