In a nutshell, the focus of my research is on integrative human physiology. Within this area I have several main areas of research:
All of my work is done with human participants and patients and we primarily use non-invasive techniques to understand the physiology.
Cerebral Blood Flow Regulation
For the last 20 years I have been interested in cerebral blood flow regulation. Maintaining proper cerebral blood flow is essential for not only life, but proper cognitive function. Cerebral blood flow regulation involves several regulatory systems. 1) Cerebral autoregulation which responds to pressure changes; 2) Autonomic controls of cerebral circulation which remains controversial; 3) Endothelial mediated dilation of the cerebral vessels; and 4) neurovascular coupling in the cerebral circulation.
My lab focuses on contributing both to the basic understanding of the physiology of the cerebral circulation in humans as well as the pathophysiology of many conditions. Our lab has demonstrated that cerebral blood flow decreases prior to syncope, even though cerebral autoregulation remains intact. That cerebral autoregulation is unaffected by aging and may actually be improved in hypertension. We also found that autoregulation is impaired in subarachnoid hemorrhage and this impairment may occur prior to the development of vasospasm.
Our current work is looking at cerebral blood flow regulation in concussion/mTBI and in Veterans who were exposed to a blast wave. We have been focusing on a detecting early changes in cerebral blood flow regulation and how this might be used as both an early diagnostic as well as a target for treatment. In addition we are currently studying the long term physiological effects of mTBI to better understand the chronic symptoms that sometimes persist.
Examining the role of the Vestibular System in Cardiovascular and Cerebrovascular Control
Humans have evolved to spend the majority of their waking hours in the upright posture. Since this means the brain is now above the heart, the generator of blood pressure, human brains must adapt to a lower perfusion pressure because of gravity. Thus every time we move from the supine to upright posture, our cerebral blood vessels must dilate to deal with the lower pressure. The vestibular system tells up about our position in space and relative to gravity. I am interested in examining the role that the vestibular system may play in assisting in the dilation of cerebral blood vessels to maintain brain blood flow.
I have previously found that stimulating the vestibular system causes changes in cerebral blood flow (BMC Neuroscience, 2009). Thus, loss of vestibular function, common in many conditions including head trauma, aging, etc, could result in reduced brain blood flow when upright, possibly explaining some of the cognitive impairment we see in these groups. My interest in this stems from my work to understand Post Spaceflight Orthostatic Intolerance. Astronauts who are extremely healthy, have trouble standing for 10 min, even if they were only in space for 14 days. A possible reason for this rapid loss of the adaptation to the upright posture may be because they have adapted to zero gravity by no longer sensing the gravity vector. So when they return to earth they are no longer dilating cerebral blood vessels when they stand up.
I am very interested in better understanding how vestibular loss may be involved in the development of reduced brain blood flow.
Assessing Vestibular Loss and Developing New Treatments
Since I believe that the vestibular system may be essential in the integrative response to maintaining brain blood flow when upright, I am interested in determining what conditions may be associated with vestibular loss that are currently being underdiagnosed. My lab did a large study of 151 individuals from 21-93 to examine otolith (part of vestibular system that senses gravity) function and found that there was a continual decline in function with each decade. This work highlights how loss of the ability to sense gravity is prevalent with aging. Interestingly, global cerebral blood flow also decreases with each decade of life. Based on my theory that brain blood flow may depend on intact otolith function, this suggests a connection with otolith loss.
We have also been working on improving otolith function using stochastic resonance (detailed below). We have been able to improve vestibular ocular reflexes using this technique as well as balance. We currently have a clinical trial to treat balance loss using this technique. We are also working to see if improve otolith function with stochastic resonance could also improve brain blood flow when upright.
Enhancing Neural Systems Using Stochastic Resonance
Stochastic Resonance is a novel physics principle that when applied to neural systems has been found to enhance their function. The basis of stochastic resonance is that if you apply low levels of random stimulus to a neural system it makes that system more sensitive and restores lost function. Using this principle I have been able to enhance function in several neural systems. We have successfully improved the vestibular system (essential for balance) in elderly and patients with balance impairments. Using this specialized stimulation we have been able to improve ocular torsion, a vestibular ocular reflex mediated by the otoliths, something that no one has previously done. Based on this success I now am performing a clinical trial to develop a portable device to improve balance that is funded by the department of defense.
Using the same stochastic resonance principle we have been able to also improve sensory function in the feet. We have been able to improve vibration perception threshold in a variety of participants including healthy controls, elderly and even patients with diabetic neuropathy. Peripheral neuropathy is a difficult to treat condition and our work using stochastic resonance may provide a novel method of treatment. We are currently looking at expanding this program to examine other neurodegenerative diseases as well.
Sex Differences in Human Physiology
An important consideration in integrative human physiology that has been understudied is sex differences. My lab is very interested in understanding how physiological response differ between men and women. In addition we believe that understanding these differences could help us to understand some of the differences in prevalence of conditions such as stroke, headache, etc. I have previously found that cerebral autoregulation is better in women than men of all ages. We have also reported that women show greater declines in otolith function with age than men. These findings highlight the importance of considering sex in physiological research. We are currently expanding to also consider race as another factor.
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