Pittsburgh Claude D. Pepper Older Americans Independence Center

Integrative Systems Core (ISC)

Problems of mobility and balance in the aged require multidisciplinary study because they are complex and multifactorial. Advances require integrating expertise and technical resources from biomechanics, physiology, neural control of movement and biology. Thus, the goal of the Integrative Systems Core (ISC), previously referred to as the “Technology” Core, is to provide integrative, multidisciplinary knowledge, skills and techniques that foster an understanding of the biomechanical, structural, functional, physiological and biological influences on age-related mobility and balance.


ISC Leadership

Core Leader: Caterina Rosano, MD, MPH, is the Core Leader. She is a tenured Associate Professor in Epidemiology and a previous RCDC Scholar. She has been an NIH independently funded investigator for over 10 years, with two NIH R01s investigating the neuroimaging features related to mobility in the elderly, one R01 investigating the neurologic basis of mobility in type 1 diabetes patients and other projects to quantify brain health with neuroimaging in response to exercise and vascular diseases. She directs the eBrain lab (neuro/epi expertise).

Core Co-leader: Tim Greenamyre MD, PhD, is Professor and Vice Chair of Neurology, Director of VA PIND (Pittsburgh Institute for Neurodegenerative Disease), UPMC Endowed Professor and Chief, Movement Disorders, is the Co-leader of the ISC. He is Co-director of the Biology of Mobility/Aging Workgroup, Co-PI of a mitochondrial injury pilot project and mentor for Laurie Sanders, PhD, a proposed Pepper KL2 Scholar. His main interest is in Parkinson’s and movement disorders.

Internal Operations Committee: The Internal Operations Committee (IOC) consists of the Core Leaders and the Core faculty directors of each lab. The IOC plans, implements and evaluates the services of the ISC. The IOC determines priorities for allocation of resources for proposed new projects (EP or Pepper-related) based on relevance to our theme and quality of the work. It assists with pre-award planning and develops cost estimates for use of its resources. The IOC also identifies needs for new techniques and prioritizes Developmental Projects.

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Highlights and Innovations

Over the last cycle we have helped pioneer novel imaging, innovative non-invasive technology that can be used during movement, new ways to assess gait and examine gait variability and utilized techniques to examine oxidative capacity within skeletal muscle.

  • Neuroimaging: ISC is actively involved in technical support from the Neuroimaging labs (MR Research Center, GPN-MRI Processing, eBRAIN, see Resources). We invested in the development of an Automated Labeling Program that allows us to precisely measure regional gray matter and white matter intensity volumes. We further developed software to assess white matter tract integrity using Diffusion Tensor Imaging. We have protocols for assessing cognitive function during MRI using a modified Stroop task. Structural and functional MRI methods have been employed in several NIA-funded studies of Dr. Rosano. For the project on stepping while conducting MRI studies, an MR-compatible force plate has been developed to measure postural responses during functional MRI. This system will augment our ongoing work in structural neuroanatomy of mobility. Furthermore Dr. Kirk Erickson’s work on improvement in cognition following exercise has been supported by the Neuroimaging Labs and resulted in a high impact study in PNAS entitled: “Exercise training increases the size of the hippocampus and improves memory”.
  • Near-Infrared Spectroscopy (NIRS): NIRS is a non-invasive technique developed by Dr. Huppert (Optical Brain Imaging lab) to measure brain activity using light. Two independent laser colors/signals are sensitive to oxyhemoglobin and deoxyhemoglobin changes in the brain. The information provides data associated with structural and functional MRI. This more portable technique can be used during movement and has recently been extended to study movement and cognition in long-term care residents. Pilot funds supported successful R21 and R01 applications for Dr. Huppert, and a new CTSI KL2 for Dr. Andi Rosso to examine NIRS in community seniors.
  • Assessment of gait and gait measures developed at Pitt: iGait is a portable, low cost, smart phone device for monitoring gait and gait speed developed by Dr. Sejdic (iMED lab) and is currently being used in the LTC pilot study of balance and gait assessment (Drs. Sparto, Huppert, Greenspan). We have examined innovative ways to quantify the motor control and the timing and coordination of gait. Specifically, we have advanced the field in the areas of gait variability and smoothness of walking. This work was instrumental in Dr. Brach obtaining her PCORI funding and both measures will be outcomes in her cluster randomized trial.
  • Our Biomechanics labs (Human Movement and Balance) have supported the development of new measures of mobility including the Figure of 8 Walk Test and the Modified Gait Efficacy Scale. The Figure of 8 Walk test, a measure motor skill in walking, has been used as an outcome measure in a clinical trial of exercise and will be used in the PCORI study by Dr. Brach. The Modified Gait Efficacy Scale was designed to assess walking confidence under challenging everyday circumstances. It has been used as an outcome in a clinical trial of exercise and observational studies of seniors.
  • Skeletal muscle studies and function in older adults: Loss of walking ability with aging may be related to a reduced oxidative capacity within skeletal muscle. The ISC Endocrinology and Metabolism Clinical Research Laboratory (previously directed by Dr. Bret Goodpaster and now by Dr. Fred Toledo) supported the pilot study by Dr. Coen to examine impaired fatty acid metabolism in aging muscle. This work led to a K01 for Dr. Coen to investigate ceramide medicated oxidative stress in muscle loss with aging. In the previous cycle, we supported the NIH ARRA funded challenge grant, Study of Energy and Aging (SEA), and established a protocol for measuring mitochondrial function with MR spectroscopy. We are extending development of this method in Health ABC (Hetherington) to examine mitochondrial function in muscle biopsy.
  • DNA damage derived aging is due in part to NF-kB activation: The Pepper pilot studies from Dr. Huard, Neidernhofer and Robbins (McGowan Stem Cell Center) demonstrated that DNA damage derived aging due to NF-kB activation is attenuated by IKK/NF-kB inhibitors. This led to a P01 (AG043376) and their work was reported in a high impact journal, Journal of Clinical Investigation, in an article entitled: “NF-kappa B inhibition delays DNA damage-induced senescence and aging in mice.

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Core Facilities

The facilities included in the Integrative Systems Core of the Pittsburgh OAIC are divided into 4 domains and include 1) Neuroimaging, 2) Biomechanics, 3) Physiology/Exercise and 4) Biology. They all support our OAIC theme of mobility, balance and aging.

Facility Directors Position/Dept Description
Neuroimaging
MR Research Center Hoby Hetherington, PhD Prof Radiology MRI-brain, muscle (7T), fMRI, step testing MRI
GPN-MRI Processing Lab Howard Aizenstein, MD, PhD Assoc Prof Psychiatry MRI- aging neuroimaging/analysis & functional imaging
Optical Brain Imaging Ted Huppert, PhD Asst Prof Bioengineering Near-Infrared Spectroscopy (NIRS)
eBRAIN Caterina Rosano, MD, MPH Assoc Prof Epi Neuro-epidemiology
Biomechanics
Human Movement Laboratory Rakié Cham, PhD Assoc Prof Engineering Locomotion, biomechanical gait assessments
Human Balance Laboratory Mark S. Redfern, PhD Prof Bioengineering, Vice Provost Univ of Pgh Postural Control
Medical Virtual Reality Center Patrick Sparto, PT, PhD Assoc Prof PT Visual proprioceptive inputs to study sensory integration for balance and muscle
iMED Ervin Sejdic, PhD Asst Prof Elec and Comp Engineering Non-invasive diagnosis and monitoring cerebral blood flow, iGait gait assessment
Physiology/Exercise
Endocrinology and Metabolism Clinical Research Laboratory Fred Toledo, MD Asst Prof Med Fitness testing, body composition, substrate metabolism, muscle biopsy
Bach lab Kirk Erickson, PhD Assoc Prof Psych Exercise, cognitive, neuropsych testing, fMRI
Physical Activity Weight Management Center John Jakicic, PhD Prof, Chair, Health and Physical Activity Energy expenditure, body composition, exercise
Biology
McGowan Center/ Stem Cell Research Johnny Huard, PhD Prof and Vice Chair, Ortho Surgery Tissue engineering, stem cell research, cellular therapies, animal facilities
PIND Tim Greenamyre, MD, PhD Prof, Vice Chair, Neurology Labs for neural cell death, mitochondrial dysfunction, genetic modeling

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