The objective is to determine how damaged brain autonomic nervous system (ANS) regulatory areas (hypothalamus, insula cortex, and cerebellum) respond to an ANS challenge, and to assess the laterality of functional responses to that challenge in heart failure (HF) subjects. Abnormal autonomic nervous system activity in HF is associated with increased morbidity and mortality. It is unclear if the structural damage seen in central ANS control regions reflects functional ANS abnormalities. Our preliminary studies found that injury in ANS control regions was accompanied by lateralized, altered (blunted, inverted, or time-delayed) functional deficits to ANS challenges in HF, and these changes preferentially occurred on the right side. The lateralization of damage and impaired functional responses on the right-side can increase risk for cardiac dysrhythmias and increase ANS abnormalities. However, responses of these damaged brain regions to ANS challenges are unclear, and the extent to which the lateralized injury contributes to abnormal ANS reactivity in HF has yet to be described. Therefore, using a two-group comparative design, we will examine the structural integrity in brain ANS control areas using diffusion tensor imaging procedures and functional responses and laterality of those signal changes to an ANS challenge using functional magnetic resonance imaging (MRI) procedures in 40 HF and 40 age- and gender-matched healthy controls.
The specific aims are to:1) evaluate functional responses to an ANS challenge eliciting sequential sympathetic and parasympathetic actions (Valsalva maneuver) in a set of ANS regulatory brain regions (hypothalamus, insular cortices, and cerebellum) using functional MRI procedures in HF and healthy controls;2) evaluate the relationships between structural integrity (using diffusion tensor imaging procedures) and functional activity (via functional MRI) of brain regions which regulate ANS tone in HF subjects. These studies will aid in the identification, development, and evaluation of new therapeutic strategies to protect and retrain central nervous system regions to restore ANS function, and improve survival and quality of life in this high risk patient population. Potential future interventions for these structural and functional ANS abnormalities could include peripheral or centrally-acting pharmacologic agents (such as statins or angiotensin-renin blockers), or neuroprotective interventions, including retraining/reorganization of alternative brain structures to restore ANS brain functions.

Public Health Relevance

Heart failure patients show severe autonomic control irregularities, which are linked to increased morbidity and mortality, and may result from injury t autonomic regulatory brain sites. Determination of relationships between structural injury in autonomic control areas and aberrant functional responses to an autonomic challenge has the potential to disclose the processes contributing to abnormal autonomic control in the condition. [Understanding of the relationships between structural brain injury and functional consequences will assist in the identification of appropriate interventions to limit further brain injury, or reover brain functions which have the potential to impact morbidity and mortality and quality of life in this high risk patient population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Project (R01)
Project #
5R01NR013625-03
Application #
8677626
Study Section
Nursing and Related Clinical Sciences Study Section (NRCS)
Program Officer
Huss, Karen
Project Start
2012-09-27
Project End
2016-06-30
Budget Start
2014-07-09
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
$426,310
Indirect Cost
$148,713
Name
University of California Los Angeles
Department
Type
Schools of Nursing
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Song, Xiaopeng; Roy, Bhaswati; Fonarow, Gregg C et al. (2018) Brain structural changes associated with aberrant functional responses to the Valsalva maneuver in heart failure. J Neurosci Res 96:1610-1622
Roy, Bhaswati; Woo, Mary; Kumar, Rajesh (2018) Cerebral blood flow in the central autonomic network: is there any effect of hemispheric lateralization in patients with heart failure? Reply. Eur J Heart Fail 20:830-831
Roy, Bhaswati; Woo, Mary A; Wang, Danny J J et al. (2017) Reduced regional cerebral blood flow in patients with heart failure. Eur J Heart Fail 19:1294-1302
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Park, Bumhee; Roy, Bhaswati; Woo, Mary A et al. (2016) Lateralized Resting-State Functional Brain Network Organization Changes in Heart Failure. PLoS One 11:e0155894
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Kumar, Rajesh; Yadav, Santosh K; Palomares, Jose A et al. (2015) Reduced regional brain cortical thickness in patients with heart failure. PLoS One 10:e0126595
Woo, Mary A; Palomares, Jose A; Macey, Paul M et al. (2015) Global and regional brain mean diffusivity changes in patients with heart failure. J Neurosci Res 93:678-85
Woo, Mary A; Ogren, Jennifer A; Abouzeid, Christiane M et al. (2015) Regional hippocampal damage in heart failure. Eur J Heart Fail 17:494-500
Harper, Ronald M; Kumar, Rajesh; Macey, Paul M et al. (2014) Affective brain areas and sleep-disordered breathing. Prog Brain Res 209:275-93

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