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Project Title:  Vestibular-Cerebrovascular Interactions and Their Contribution to Post-Spaceflight Orthostatic Intolerance Reduce
Fiscal Year: FY 2009 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/16/2004  
End Date: 08/23/2009  
Task Last Updated: 09/13/2010 
Download report in PDF pdf
Principal Investigator/Affiliation:   Serrador, Jorge Manuel Ph.D. / Harvard Medical School 
Address:  BIDMC - Palmer 117 
One Deaconess Road 
Boston , MA 02215 
Email: serrador@hms.harvard.edu 
Phone: 617/632-8843  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Harvard Medical School 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Black, Owen  Legacy Health System 
Lipsitz, Lewis  Hebrew Rehabiliation Center for Aged  
Schlegel, Todd  NASA Johnson Space Center 
Wood, Scott  Naval Aerospace Medical Research Laboratory  
Key Personnel Changes / Previous PI: None
Project Information: Grant/Contract No. NNJ04HI13G 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
Grant/Contract No.: NNJ04HI13G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) OI:Risk of Orthostatic Intolerance during Re-Exposure to Gravity
Human Research Program Gaps: (1) CV03:Is orthostatic intolerance a potential hazard?
Flight Assignment/Project Notes: NOTE: Received NCE to 08/23/2009 per J. Dardano/JSC (8/08)

Task Description: Post-spaceflight orthostatic intolerance, a principal NASA safety concern, is a complex multi-factorial problem that continues to be poorly understood. Recent evidence clearly suggests that the vestibular otolith system, which is directly affected by spaceflight, assists in both autonomic and blood pressure regulation during orthostatic stress. Vestibular activation has also has direct effects on cerebral blood flow suggesting that vestibular inputs also affect the cerebrovascular response to orthostasis. The goal of this research is to examine the role of vestibular inputs in cerebral blood flow regulation and the effect of these inputs on orthostatic tolerance. Our general hypothesis is that otolith mediated vestibular inputs act as a feed forward mechanism causing cerebral vasodilation to compensate for the decrease in cerebral perfusion pressure during the upright posture. This project's four specific aims are to: 1) Determine the effect of tilts in the pitch plane with and without visual feedback on cerebral blood flow and cerebral autoregulation in healthy elderly with and without vestibular hypofunction and healthy young subjects.; 2) Determine the effect of otolith vs otolith and canal stimulation on cerebral blood flow in healthy elderly with and without vestibular hypofunction and healthy young subjects. This aim will be accomplished by varying the radius of rotation of subjects on a short arm centrifuge; 3) Determine the effect of canal vs canal and otolith stimulation on cerebral blood flow in elderly subjects with normal and reduced vestibular function. This aim will be accomplished by using earth vertical axis rotations vs. head tilt while supine or prone; 4) Determine the effect of training subjects to associate otolith input as tilt on cerebral blood flow during orthostatic stress in elderly subjects with intact and impaired vestibular function. This aim will be accomplished by training subjects with tilt or centrifugation to interpret otolith signals as either translation or tilt by providing visual scenes to reinforce this perception. The results of these studies will provide direct evidence on the role of vestibular inputs in cerebrovascular regulation. This work may lead to new methods to diagnose and treat not only post-spaceflight orthostatic intolerance but also the ~500,000 otherwise healthy subjects that are affected by orthostatic intolerance.

Research Impact/Earth Benefits: Understanding the causes of orthostatic intolerance will directly benefit two groups of individuals. First, elderly individuals have increased risks of falls which are associated with decreased quality of life and increased mortality. Falls are the leading cause of death for older adults. In fact, Almost 11,000 older adults a year, or 30 each day, die from a falls injury. Half of those who survive a fall never return to their prior level of mobility or independence. By reducing the likelihood that an elderly individual will fall due to light headedness, i.e. orthostatic intolerance, we will be able to improve the quality of life and reduce the rate of fall induced mortality in this group, a significant advance for the aging population. In addition, almost 500,000 Americans suffer from orthostatic intolerance, often with poor treatment outcomes. Currently a possible vestibular role for orthostatic intolerance is not considered. This research could not only highlight a new cause of orthostatic intolerance but lead to new treatments including vestibular rehabilitation, etc.

Task Progress & Bibliography Information FY2009 
Task Progress: Introduction:

Post spaceflight orthostatic intolerance is an important NASA safety concern with as many as 60% of returning astronauts experiencing symptoms of cerebral hypoperfusion. While the mechanisms underlying this problem are likely multifactorial, the goal of this research is to examine the role of vestibular inputs in cerebral blood flow regulation and the effect of these inputs on orthostatic tolerance. Our general hypothesis is that otolith mediated vestibular inputs act as a feed forward mechanism causing cerebral vasodilation to compensate for the decrease in cerebral perfusion pressure caused by the upright posture. We proposed four specific aims to address this hypothesis.

Specific Aim 1: Determine the effect of orthostatic stress (tilts) on cerebral blood flow and cerebral autoregulation in elderly subjects with intact and impaired vestibular function. The purpose of this aim was to determine whether the vestibular system plays an important role in the changes in cerebral blood flow when you go from a supine to upright.

Major Finding: Loss of vestibular function in both younger and older subjects is associated with greater decreases in cerebral blood flow when upright.

Implications for Human Spaceflight: 1) Sensorimotor disturbances related to adaptation to microgravity are common among astronauts and may result in greater drops in cerebral blood flow when astronauts are upright upon returning to a 1-G environment

Specific Aim 2: Determine the effect of static otolith stimulation on cerebral blood flow. The purpose of this aim was to determine whether continual stimulation of the otoliths without associated canal or other sensorimotor cues affects cerebral blood flow. This aim was accomplished by performing centrifugation to selectively stimulate the otoliths.

Major Finding: Changes in cerebral blood flow were consistent during otolith stimulation, even in the absence of other cues of tilt.

Implications for Human Spaceflight: 1) Vestibular adaptations that occur during spaceflight could result in reduced otolith inputs and maladaptive cerebral blood flow responses. Since cerebral blood flow changes occur during otolith stimulation in the absence of other cues of tilt, astronauts may be at greatest risk for orthostatic intolerance post spaceflight if other sensory cues of upright are missing to replace impaired otolith cues.

Specific Aim 3: Determine the effect of dynamic canal plus otolith vs otolith stimulation on cerebral blood flow. This aim was accomplished by examining cerebral blood during both centrifugation (otolith stimulation) vs dynamic pitch tilt (otolith and canal stimulation) in a group of young subjects with intact vestibular function.

Major Finding: Changes in cerebral blood flow were mediated primarily by otolith activation.

Implications for Human Spaceflight: 1) Since vestibular adaptation to microgravity involves changes in interpretation of otolith and not canal cues, this further supports the possibility that changes in otolith inputs could cause problems in cerebral blood flow regulation

Specific Aim 4: Determine the effect of training subjects to associate otolith input as tilt on cerebral blood flow during orthostatic stress in elderly subjects with intact and impaired vestibular function. The goal of this aim is to determine if enhancing vestibular function could be used as a countermeasure to improve cerebral blood flow when upright.

Major Finding: Stimulation of the vestibular nerve with subsensory stochastic noise causes improvement in both vestibular function and cerebral blood flow responses to tilt.

Implications for Human Spaceflight: 1) Greater reductions in cerebral blood flow associated with reduced vestibular function post spaceflight could be reduced by stimulation of the vestibular nerve

Bibliography Type: Description: (Last Updated: 10/31/2019)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Serrador JM, Lipsitz L, Black FO, Wood SJ. "Decreases in Cerebral Blood Flow When Upright Are Related to Vestibular Function Regardless of Age." Presented at Experimental Biology 2009, New Orleans, LA, April 18-22, 2009.

FASEB Journal 2009 Apr;23(1):613.35. http://www.fasebj.org/cgi/content/meeting_abstract/23/1_MeetingAbstracts/613.35?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=serrador&searchid=1&FIRSTINDEX=0&volume=23&issue=1_MeetingAbstracts&resourcetype=HWCIT , Apr-2009

Abstracts for Journals and Proceedings Serrador JM, Breen PP, ÓLaighin G, Deegan B, Geraghty M, Wood SJ. "Enhancing Neural Signals with Stochastic Resonance Electrical Stimulation." Presented at 20th International American Autonomic Society Meeting, St. Thomas, U.S. Virgin Islands, November, 2009

20th International American Autonomic Society Meeting, St. Thomas, U.S. Virgin Islands, November, 2009. , Nov-2009

Articles in Peer-reviewed Journals Serrador JM, Deegan BM, Geraghty MC, Wood SJ. "Enhancing vestibular function in the elderly with imperceptible electrical stimulation." Sci Rep. 2018 Jan 10;8(1):336. https://doi.org/10.1038/s41598-017-18653-8 ; PubMed PMID: 29321511; PubMed Central PMCID: PMC5762876 , Jan-2018
Articles in Peer-reviewed Journals Serrador JM, Schlegel TT, Black FO, Wood SJ. "Vestibular effects on cerebral blood flow. " BMC Neurosci. 2009 Sep 23;10:119. PMID: 19775430 , Sep-2009
Articles in Peer-reviewed Journals Serrador JM, Lipsitz LA, Gopalakrishnan GS, Black FO, Wood SJ. "Loss of otolith function with age is associated with increased postural sway measures." Neurosci Lett. 2009 Nov 6;465(1):10-5. PMID: 19716400 , Oct-2009
Articles in Peer-reviewed Journals Deegan BM, Devine ER, Geraghty MC, Jones E, ÓLaighin G, Serrador JM. "The relationship between cardiac output and dynamic cerebral autoregulation in humans." J Appl Physiol (1985). 2010 Nov;109(5):1424-31. Epub 2010 Aug 5. https://doi.org/10.1152/japplphysiol.01262.2009 ; PubMed PMID: 20689094; PubMed Central PMCID: PMC2980368 , Nov-2010
Articles in Peer-reviewed Journals Deegan BM, Geraghty MC, Hodgeman RM, Reisner AA, O'Laighin G, Serrador JM. "Assessment of techniques used to evaluate the effect of posture and cardiac output on Cerebral Autoregulation." Conf Proc IEEE Eng Med Biol Soc. 2008;2008:1992-5. PMID: 19163083 (Engineering in Medicine and Biology Society, 2008. EMBS 2008. 30th Annual International Conference of the IEEE) , Aug-2008
Significant Media Coverage Serrador JM. "'Astronauts and the Elderly', interview with Dr. Jorge Serrador." Radio New Zealand: Our Changing World. Thursday Oct. 22, 2009. http://www.radionz.co.nz/national/programmes/ourchangingworld/20091022 , Oct-2009
Project Title:  Vestibular-Cerebrovascular Interactions and Their Contribution to Post-Spaceflight Orthostatic Intolerance Reduce
Fiscal Year: FY 2008 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/16/2004  
End Date: 08/23/2009  
Task Last Updated: 01/12/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   Serrador, Jorge Manuel Ph.D. / Harvard Medical School 
Address:  BIDMC - Palmer 117 
One Deaconess Road 
Boston , MA 02215 
Email: serrador@hms.harvard.edu 
Phone: 617/632-8843  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Harvard Medical School 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Black, Owen  Legacy Health System 
Lipsitz, Lewis  Hebrew Rehabiliation Center for Aged  
Schlegel, Todd  NASA Johnson Space Center 
Wood, Scott  Naval Aerospace Medical Research Laboratory  
Key Personnel Changes / Previous PI: None
Project Information: Grant/Contract No. NNJ04HI13G 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
Grant/Contract No.: NNJ04HI13G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) OI:Risk of Orthostatic Intolerance during Re-Exposure to Gravity
Human Research Program Gaps: (1) CV03:Is orthostatic intolerance a potential hazard?
Flight Assignment/Project Notes: NOTE: Received NCE to 08/23/2009 per J. Dardano/JSC (8/08)

Task Description: Post-spaceflight orthostatic intolerance, a principal NASA safety concern, is a complex multi-factorial problem that continues to be poorly understood. Recent evidence clearly suggests that the vestibular otolith system, which is directly affected by spaceflight, assists in both autonomic and blood pressure regulation during orthostatic stress. Vestibular activation has also has direct effects on cerebral blood flow suggesting that vestibular inputs also affect the cerebrovascular response to orthostasis. The goal of this research is to examine the role of vestibular inputs in cerebral blood flow regulation and the effect of these inputs on orthostatic tolerance. Our general hypothesis is that otolith mediated vestibular inputs act as a feed forward mechanism causing cerebral vasodilation to compensate for the decrease in cerebral perfusion pressure during the upright posture. This project's four specific aims are to: 1) Determine the effect of tilts in the pitch plane with and without visual feedback on cerebral blood flow and cerebral autoregulation in healthy elderly with and without vestibular hypofunction and healthy young subjects.; 2) Determine the effect of otolith vs otolith and canal stimulation on cerebral blood flow in healthy elderly with and without vestibular hypofunction and healthy young subjects. This aim will be accomplished by varying the radius of rotation of subjects on a short arm centrifuge; 3) Determine the effect of canal vs canal and otolith stimulation on cerebral blood flow in elderly subjects with normal and reduced vestibular function. This aim will be accomplished by using earth vertical axis rotations vs. head tilt while supine or prone; 4) Determine the effect of training subjects to associate otolith input as tilt on cerebral blood flow during orthostatic stress in elderly subjects with intact and impaired vestibular function. This aim will be accomplished by training subjects with tilt or centrifugation to interpret otolith signals as either translation or tilt by providing visual scenes to reinforce this perception. The results of these studies will provide direct evidence on the role of vestibular inputs in cerebrovascular regulation. This work may lead to new methods to diagnose and treat not only post-spaceflight orthostatic intolerance but also the ~500,000 otherwise healthy subjects that are affected by orthostatic intolerance.

Research Impact/Earth Benefits: Understanding the causes of orthostatic intolerance will directly benefit two groups of individuals. First, elderly individuals have increased risks of falls which are associated with decreased quality of life and increased mortality. Falls are the leading cause of death for older adults. In fact, Almost 11,000 older adults a year, or 30 each day, die from a falls injury. Half of those who survive a fall never return to their prior level of mobility or independence. By reducing the likelihood that an elderly individual will fall due to light headedness, i.e. orthostatic intolerance, we will be able to improve the quality of life and reduce the rate of fall induced mortality in this group, a significant advance for the aging population. In addition, almost 500,000 Americans suffer from orthostatic intolerance, often with poor treatment outcomes. Currently a possible vestibular role for orthostatic intolerance is not considered. This research could not only highlight a new cause of orthostatic intolerance but lead to new treatments including vestibular rehabilitation, etc.

Task Progress & Bibliography Information FY2008 
Task Progress: In the past 12 months we have completed three of four specific aims. After performing 160 vestibular screenings on 100 young (age 21+) and 60 elderly (age 60+) subjects we were able to select a group of younger and older subjects with normal and impaired otolith function. From these screenings we have found two major findings. First, there were significant levels of vestibular impairment even in younger individuals, which became worse as individuals became older. Second, the rate of decline of otolith function in females was double to that seen in males.

In addition, we found a strong relationship between sway parameters and otolith function. Thus, individuals with the worst otolith function tended to show the greatest sway. These increased levels of sway suggested they were also at greater risk for falls. Thus, elderly individuals with impaired vestibular function may be at even greater risk for falls. Testing a group of elderly subjects with normal and impaired vestibular function found that the group with impaired function demonstrated a significantly greater drop in brain blood flow when upright. In addition this greater drop only occurred when they were blindfolded and had no visual information. This would suggest that individuals with loss of vestibular function may have problems maintaining brain blood flow when upright. In addition, this impairment only occurs when they are unable to use vision in place of vestibular information to tell them about whether they are upright or not. Finally, we have tested a group of young subjects with and without impairment, but not yet analyzed the data.

We have already completed specific aim 2 by performing variable-radius centrifugation on a group of healthy subjects. While rotation on center did not cause any changes in brain blood flow, movement forward, causing the perception of forward tilt, and resulted in a significant decrease in brain blood flow. This decrease in brain blood flow could not be explained by any other physiological responses, indicating that vestibular inputs were likely the cause. To complete Specific Aim 3 we used a combination of dynamic tilt and variable radius centrifugation to separate the roles of otoliths vs canals in the brain blood flow response to vestibular stimulation. Brain blood flow oscillated with the frequency of motion, again suggesting an important role for vestibular inputs in this response. In addition, changes at higher and lower frequencies were similar between tilt and centrifugation. Since centrifugation at low frequencies has minimal canal inputs, these data suggest that the response was primarily driven by otolith inputs.

In addition, during the previous year we were able to develop a new method of stimulating the vestibular system to increase performance. In the last year of the grant we plan to test our stimulator to determine if it could be used as a new treatment paradigm for vestibular loss with the intention of working towards a countermeasure.

Bibliography Type: Description: (Last Updated: 10/31/2019)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Serrador JM, Gopalakrishnan GS, Black FO, Lipsitz LA, Wood SJ. "Effect of vestibular impairment on cerebral blood flow response to dynamic roll tilt." International Autonomic Neuroscience Meeting, Vienna, Austria. 2007.

International Autonomic Neuroscience Meeting, Vienna, Austria. 2007. , Oct-2007

Articles in Peer-reviewed Journals Serrador JM, Lipsitz LA, Gopalakrishnan GS, Black FO, Wood SJ. "Loss of Otolith Function with Age is associated with Increased Postural Sway Measures." Neuroscience Letters (in review), January 2009. , Jan-2009
Articles in Peer-reviewed Journals Serrador JM, Schlegel TT, Black FO, Wood SJ. "Vestibular effects on Cerebral Blood Flow." BMC Neuroscience (in review), January 2009. , Jan-2009
Project Title:  Vestibular-Cerebrovascular Interactions and Their Contribution to Post-Spaceflight Orthostatic Intolerance Reduce
Fiscal Year: FY 2007 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/16/2004  
End Date: 08/23/2008  
Task Last Updated: 05/09/2007 
Download report in PDF pdf
Principal Investigator/Affiliation:   Serrador, Jorge Manuel Ph.D. / Harvard Medical School 
Address:  BIDMC - Palmer 117 
One Deaconess Road 
Boston , MA 02215 
Email: serrador@hms.harvard.edu 
Phone: 617/632-8843  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Harvard Medical School 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Black, Owen  Legacy Health System 
Lipsitz, Lewis  Hebrew Rehabiliation Center for Aged  
Schlegel, Todd  NASA Johnson Space Center 
Wood, Scott  Naval Aerospace Medical Research Laboratory  
Key Personnel Changes / Previous PI: None
Project Information: Grant/Contract No. NNJ04HI13G 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
Grant/Contract No.: NNJ04HI13G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) OI:Risk of Orthostatic Intolerance during Re-Exposure to Gravity
Human Research Program Gaps: (1) CV03:Is orthostatic intolerance a potential hazard?
Task Description: Post-spaceflight orthostatic intolerance, a principal NASA safety concern, is a complex multi-factorial problem that continues to be poorly understood. Recent evidence clearly suggests that the vestibular otolith system, which is directly affected by spaceflight, assists in both autonomic and blood pressure regulation during orthostatic stress. Vestibular activation has also has direct effects on cerebral blood flow suggesting that vestibular inputs also affect the cerebrovascular response to orthostasis. The goal of this research is to examine the role of vestibular inputs in cerebral blood flow regulation and the effect of these inputs on orthostatic tolerance. Our general hypothesis is that otolith mediated vestibular inputs act as a feed forward mechanism causing cerebral vasodilation to compensate for the decrease in cerebral perfusion pressure during the upright posture. This project's four specific aims are to: 1) Determine the effect of tilts in the pitch plane with and without visual feedback on cerebral blood flow and cerebral autoregulation in healthy elderly with and without vestibular hypofunction and healthy young subjects.; 2) Determine the effect of otolith vs otolith and canal stimulation on cerebral blood flow in healthy elderly with and without vestibular hypofunction and healthy young subjects. This aim will be accomplished by varying the radius of rotation of subjects on a short arm centrifuge; 3) Determine the effect of canal vs canal and otolith stimulation on cerebral blood flow in elderly subjects with normal and reduced vestibular function. This aim will be accomplished by using earth vertical axis rotations vs. head tilt while supine or prone; 4) Determine the effect of training subjects to associate otolith input as tilt on cerebral blood flow during orthostatic stress in elderly subjects with intact and impaired vestibular function. This aim will be accomplished by training subjects with tilt or centrifugation to interpret otolith signals as either translation or tilt by providing visual scenes to reinforce this perception. The results of these studies will provide direct evidence on the role of vestibular inputs in cerebrovascular regulation. This work may lead to new methods to diagnose and treat not only post-spaceflight orthostatic intolerance but also the ~500,000 otherwise healthy subjects that are affected by orthostatic intolerance.

Research Impact/Earth Benefits: Understanding the causes of orthostatic intolerance will directly benefit two groups of individuals. First, elderly individuals have increased risks of falls which are associated with decreased quality of life and increased mortality. Falls are the leading cause of death for older adults. In fact, Almost 11,000 older adults a year, or 30 each day, die from a falls injury. Half of those who survive a fall never return to their prior level of mobility or independence. By reducing the likelihood that an elderly individual will fall due to light headedness, i.e. orthostatic intolerance, we will be able to improve the quality of life and reduce the rate of fall induced mortality in this group, a significant advance for the aging population. In addition, almost 500,000 Americans suffer from orthostatic intolerance, often with poor treatment outcomes. Currently a possible vestibular role for orthostatic intolerance is not considered. This research could not only highlight a new cause of orthostatic intolerance but lead to new treatments including vestibular rehabilitation, etc.

Task Progress & Bibliography Information FY2007 
Task Progress: To complete the specific aims laid out in the grant, the PI has had three primary goals during the last year of this grant:

1) Complete screening of elderly and young to determine normal and impaired vestibular function 2) Testing the first cohort of subjects for Specific Aim 1 and 2 while preparing for completion of Aims 1, 2 and 3 in year 3 of the grant 3) Beginning data collection in Portland, Oregon for centrifugation studies

During this past year we have continued to collect screening data and reached 160 subjects (80% of the total number expected to be enrolled). From this we have found several interesting findings already. In addition our initial data indicates that vestibular function has a direct effect on the initial response to orthostatic stress and thus may be implicated in the orthostatic intolerance problem seen in astronauts. We plan to complete specific aim 1 within the first 3 months of the current funding cycle. We anticipate we will be able to complete Specific Aim 3 by the end of August using the same group of subjects used for the tilt study.

We have begun centrifuge testing at Legacy Health Systems in Portland, Oregon (Specific Aim 2) and have present data on 10 subjects to date. As can be seen, these data further support a connection between the vestibular system and cerebrovascular regulation. We plan to complete Specific Aim 2 by the end of the current funding period.

Bibliography Type: Description: (Last Updated: 10/31/2019)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Devine ER, Milberg WP, Serrador JM. "Does gravity affect functional cerebral blood flow response? " International Cerebral Blood Flow Meeting, Amsterdam, The Netherlands, June, 2005

Journal of Cerebral Blood Flow & Metabolism 2005 Aug ;25(Suppl 1):S384 -4. http://dx.doi.org/10.1038/sj.jcbfm.9591524.0384 , Aug-2005

Abstracts for Journals and Proceedings Devine ER, Serrador JM. "Relationship between Stroke Volume and Cerebral Blood Flow During Pressure Changes in Humans." XXXV International Congress of Physiological Sciences, April 2005.

FASEB Journal 2005; 19(5) A1257. , May-2005

Abstracts for Journals and Proceedings Gopalakrishnan GS, Baker E, Serrador JM, Wood SJ. "Impaired Vestibular Function affects Orthostatic Cerebral Blood Flow Response. " Experimental Biology, Washington DC, April 2007.

FASEB J, 2007 Apr; 21:A1383-4. , Apr-2007

Articles in Peer-reviewed Journals Serrador JM, Wood SJ. "Vasopressin: neurohumoral link between nausea and motion sickness. Author reply." Aviat Space Environ Med. 2005 Aug;76(8):805; author reply 805-6. PMID: 16110700 , Aug-2005
Articles in Peer-reviewed Journals Serrador JM, Schlegel TT, Black FO, Wood SJ. "Cerebral hypoperfusion precedes nausea during centrifugation." Aviat Space Environ Med. 2005 Feb;76(2):91-6. PMID: 15742822 , Feb-2005
Project Title:  Vestibular-Cerebrovascular Interactions and Their Contribution to Post-Spaceflight Orthostatic Intolerance Reduce
Fiscal Year: FY 2006 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/16/2004  
End Date: 08/23/2008  
Task Last Updated: 02/05/2007 
Download report in PDF pdf
Principal Investigator/Affiliation:   Serrador, Jorge Manuel Ph.D. / Harvard Medical School 
Address:  BIDMC - Palmer 117 
One Deaconess Road 
Boston , MA 02215 
Email: serrador@hms.harvard.edu 
Phone: 617/632-8843  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Harvard Medical School 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Black, Owen  Legacy Health System 
Lipsitz, Lewis  Hebrew Rehabiliation Center for Aged  
Schlegel, Todd  NASA Johnson Space Center 
Wood, Scott  Naval Aerospace Medical Research Laboratory  
Key Personnel Changes / Previous PI: None
Project Information: Grant/Contract No. NNJ04HI13G 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
Grant/Contract No.: NNJ04HI13G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) OI:Risk of Orthostatic Intolerance during Re-Exposure to Gravity
Human Research Program Gaps: (1) CV03:Is orthostatic intolerance a potential hazard?
Task Description: Post-spaceflight orthostatic intolerance, a principal NASA safety concern, is a complex multi-factorial problem that continues to be poorly understood. Recent evidence clearly suggests that the vestibular otolith system, which is directly affected by spaceflight, assists in both autonomic and blood pressure regulation during orthostatic stress. Vestibular activation has also has direct effects on cerebral blood flow suggesting that vestibular inputs also affect the cerebrovascular response to orthostasis. The goal of this research is to examine the role of vestibular inputs in cerebral blood flow regulation and the effect of these inputs on orthostatic tolerance. Our general hypothesis is that otolith mediated vestibular inputs act as a feed forward mechanism causing cerebral vasodilation to compensate for the decrease in cerebral perfusion pressure during the upright posture. This project's four specific aims are to: 1) Determine the effect of tilts in the pitch plane with and without visual feedback on cerebral blood flow and cerebral autoregulation in healthy elderly with and without vestibular hypofunction and healthy young subjects.; 2) Determine the effect of otolith vs otolith and canal stimulation on cerebral blood flow in healthy elderly with and without vestibular hypofunction and healthy young subjects. This aim will be accomplished by varying the radius of rotation of subjects on a short arm centrifuge; 3) Determine the effect of canal vs canal and otolith stimulation on cerebral blood flow in elderly subjects with normal and reduced vestibular function. This aim will be accomplished by using earth vertical axis rotations vs. head tilt while supine or prone; 4) Determine the effect of training subjects to associate otolith input as tilt on cerebral blood flow during orthostatic stress in elderly subjects with intact and impaired vestibular function. This aim will be accomplished by training subjects with tilt or centrifugation to interpret otolith signals as either translation or tilt by providing visual scenes to reinforce this perception. The results of these studies will provide direct evidence on the role of vestibular inputs in cerebrovascular regulation. This work may lead to new methods to diagnose and treat not only post-spaceflight orthostatic intolerance but also the ~500,000 otherwise healthy subjects that are affected by orthostatic intolerance.

Research Impact/Earth Benefits: Understanding the causes of orthostatic intolerance will directly benefit two groups of individuals. First, elderly individuals have increased risks of falls which are associated with decreased quality of life and increased mortality. Falls are the leading cause of death for older adults. In fact, Almost 11,000 older adults a year, or 30 each day, die from a falls injury. Half of those who survive a fall never return to their prior level of mobility or independence. By reducing the likelihood that an elderly individual will fall due to light headedness, i.e. orthostatic intolerance, we will be able to improve the quality of life and reduce the rate of fall induced mortality in this group, a significant advance for the aging population. In addition, almost 500,000 Americans suffer from orthostatic intolerance, often with poor treatment outcomes. Currently a possible vestibular role for orthostatic intolerance is not considered. This research could not only highlight a new cause of orthostatic intolerance but lead to new treatments including vestibular rehabilitation, etc.

Task Progress & Bibliography Information FY2006 
Task Progress: To complete testing of the hypothesis laid out in the grant, the PI has had three primary goals during the last year of this grant:

1) Establishing a population of elderly with normal and impaired vestibular function 2) Ensuring testing for the tilt table testing and head rotation experiments could be achieved in year 3 3) Preparing to begin data collection in Portland, Oregon

Since this is a first grant for the PI, significant equipment purchases and lab setup time was required. During the first 6 months the PI was able to successfully set up a complete vestibular screening and physiology testing lab. In addition the PI was able to have several custom pieces of equipment designed to meet the screening needs of the studies. Following set-up, the subsequent time has been used to recruit and screen 108 subjects (54% of the total number expected to be enrolled).

An important piece of equipment that has been developed is the ocular counterroll chair that allows for assessment of ocular torsion. Since the primary goal of the vestibular screening is to stratify subjects by otolith function, which is the vestibular component primarily affected by spaceflight, measuring ocular torsion is essential to assessing otolith function. Dr. Wood has previously shown that using slow oscillations (+/-20 degrees @ 0.01 Hz) provides an accurate estimate of otolith function as compared to other current assessment techniques (Merfeld et al. J Neurophys 2005; 94: 199-205; Merfeld et al. J Neurophys 2005; 94: 206-218). In a recent study Dr. Wood compared ocular torsion gain during earth horizontal axis (EHA) rotation (i.e. ocular counterroll) and variable radius centrifugation (VRC). Since VRC provides an otolith specific stimulation, torsion produced by this stimulus should be solely of otolith origin. In contrast, during EHA both otolith and canal organs are activated. However, at very low frequencies, response from VRC and EHA are virtually identical. This demonstrates that ocular torsion during ocular counterroll can be used as a good measure of otolith function. In addition with the assistance of Dr. Wood, we have been able to duplicate his ocular torsion analysis system in the PI’s lab allowing us to obtain continuous ocular torsion during our screening tilt test (+/-20 degrees @ 0.01 Hz).

To address the concern of obtaining an adequate sample of elderly subjects that will allow stratification into impaired and normal vestibular function, recruitment of elderly began within the first 6 months of the grant. Ads were placed in the print publications; Harvard Cooperative Program on Aging and Boston Seniority. Recruitment flyers were also posted at the Harvard Institute for Learning in Retirement. Recruitment has subsequently increased in the past year to 50 subjects, 50% of our target population for elderly subjects. We thus believe we will not have a problem meeting our recruitment goals over the second year of the grant.

Bibliography Type: Description: (Last Updated: 10/31/2019)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Devine ER, Milberg WP, Serrador JM. "Does gravity affect functional cerebral blood flow response?" International Cerebral Blood Flow Meeting, Amsterdam, The Netherlands, June, 2005.

International Cerebral Blood Flow Meeting, 2005. , Jun-2005

Abstracts for Journals and Proceedings Devine ER, Serrador JM. "Relationship between stroke volume and cerebral blood flow during pressure changes in humans. " XXXV International Congress of Physiological Sciences, April 2005.

FASEB Journal 2005;19(5):A1257. , Apr-2005

Articles in Peer-reviewed Journals Serrador JM, Wood SJ. "Vasopressin: neurohumoral link between nausea and motion sickness. Author reply." Aviat Space Environ Med. 2005 Aug;76(8):805; author reply 805-6. PMID: 16110700 , Aug-2005
Articles in Peer-reviewed Journals Serrador JM, Schlegel TT, Black FO, Wood SJ. "Cerebral hypoperfusion precedes nausea during centrifugation." Aviat Space Environ Med. 2005 Feb;76(2):91-6. PMID: 15742822 , Feb-2005
Project Title:  Vestibular-Cerebrovascular Interactions and Their Contribution to Post-Spaceflight Orthostatic Intolerance Reduce
Fiscal Year: FY 2004 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 08/16/2004  
End Date: 08/23/2008  
Task Last Updated: 08/19/2005 
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Principal Investigator/Affiliation:   Serrador, Jorge Manuel Ph.D. / Harvard Medical School 
Address:  BIDMC - Palmer 117 
One Deaconess Road 
Boston , MA 02215 
Email: serrador@hms.harvard.edu 
Phone: 617/632-8843  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Harvard Medical School 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Black, Owen  Legacy Health System 
Lipsitz, Lewis  Hebrew Rehabiliation Center for Aged  
Schlegel, Todd  NASA Johnson Space Center 
Wood, Scott  Naval Aerospace Medical Research Laboratory  
Project Information: Grant/Contract No. NNJ04HI13G 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
Grant/Contract No.: NNJ04HI13G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) OI:Risk of Orthostatic Intolerance during Re-Exposure to Gravity
Human Research Program Gaps: (1) CV03:Is orthostatic intolerance a potential hazard?
Task Description: Post-spaceflight orthostatic intolerance, a principal NASA safety concern, is a complex multi-factorial problem that continues to be poorly understood. Recent evidence clearly suggests that the vestibular otolith system, which is directly affected by spaceflight, assists in both autonomic and blood pressure regulation during orthostatic stress. Vestibular activation has also has direct effects on cerebral blood flow suggesting that vestibular inputs also affect the cerebrovascular response to orthostasis. The goal of this research is to examine the role of vestibular inputs in cerebral blood flow regulation and the effect of these inputs on orthostatic tolerance. Our general hypothesis is that otolith mediated vestibular inputs act as a feed forward mechanism causing cerebral vasodilation to compensate for the decrease in cerebral perfusion pressure during the upright posture. This project's four specific aims are to: 1) Determine the effect of tilts in the pitch plane with and without visual feedback on cerebral blood flow and cerebral autoregulation in healthy elderly with and without vestibular hypofunction and healthy young subjects.; 2) Determine the effect of otolith vs otolith and canal stimulation on cerebral blood flow in healthy elderly with and without vestibular hypofunction and healthy young subjects. This aim will be accomplished by varying the radius of rotation of subjects on a short arm centrifuge; 3) Determine the effect of canal vs canal and otolith stimulation on cerebral blood flow in elderly subjects with normal and reduced vestibular function. This aim will be accomplished by using earth vertical axis rotations vs. head tilt while supine or prone; 4) Determine the effect of training subjects to associate otolith input as tilt on cerebral blood flow during orthostatic stress in elderly subjects with intact and impaired vestibular function. This aim will be accomplished by training subjects with tilt or centrifugation to interpret otolith signals as either translation or tilt by providing visual scenes to reinforce this perception. The results of these studies will provide direct evidence on the role of vestibular inputs in cerebrovascular regulation. This work may lead to new methods to diagnose and treat not only post-spaceflight orthostatic intolerance but also the ~500,000 otherwise healthy subjects that are affected by orthostatic intolerance.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2004 
Task Progress: New project for FY2004.

Bibliography Type: Description: (Last Updated: 10/31/2019)  Show Cumulative Bibliography Listing
 
 None in FY 2004