2. The NIH BRAIN Initiative: How It Will Help My Patients To Stop Losing Their Minds Mary A. Woo, DNSc, RN Professor – UCLA School of Nursing Disclosures: grant funding from NINR (R01 NR013625 [PI]; R01 NR014669 [PI]; R01 NR013972 [co-Inv]) and NHLBI (R01 HL113251 [co-Inv])

3. Target Patient Populations 1.Heart Failure a.Over 6 million Americans b.More than 600,000 newly diagnosed/year 2.Obstructive Sleep Apnea a.Over 12 million Americans b.Estimated UNDIAGNOSED prevalence rate is 10 million Americans 3.BOTH patient groups have increased morbidity and mortality, poor quality of life, high frequency of major depression, and impaired cognition (especially memory and executive function)

4. Primary Activities Linked To BRAIN Initiative #6. Advancing human neuroscience: 1.(Develop)/Use innovative technologies to understand the human brain and treat its disorders 2.Create and support integrated human brain research networks #7. From BRAIN Initiative to the brain: Integrate new technological and conceptual approaches produced in Goals #1-6 to discover how dynamic patterns of neural activity are transformed into cognition, emotion, perception, and action in health and disease

5. RI – right insula LI – left insula P – putamen GP – globus pallidus HF Gray Matter Loss

6. OSA Gray Matter Loss

7. Common Areas of Loss 1.Cerebellum – breathing, motor coordination 2.Cingulate – autonomic and breathing control 3.Frontal cortex - cognition

8. Figure: Increased MD values (indicating tissue injury) in insular (a), frontal cortices (b), hippocampus (c), and cerebellar areas (white circles) in HF (n = 16) compared to control subject (n = 26). (L = Left; R = Right). Mean Diffusivity (MD)

9. Figure. Global cerebellar fiber tracts in Controls (Left) and HF (right). The cerebellum (and brainstem) is located within the white ovals. Note the extensive axonal fiber loss in the males and to a lesser extent in the female HF subjects. There appears to be greater fiber loss on the right in comparison to the left in HF patients. Fiber Tractography

10. Figure. Tractography of white matter fiber tracks between the cerebellum and dorsal lateral pons. Control subject is on the left and HF on the right. Note that the control subject has more (and longer) fibers on both sides in comparison to the HF subject. Additionally, communicating fibers between the right and left tracts are significantly diminished in the HF patient.

11. Figure. Kw maps (indicator of BBB function) from a control subject and a HF patient. Multiple brain regions in HF subject show reduced Kw values compared with control subject (sites with hot vs. cool color). Blood-Brain Barrier (BBB)

12. Figure. Highlighted areas indicate sites with decreased gray matter in comparison to controls. Left: HF with SDB (AHI = 42) with significant differences in cingulate cortex, deep cerebellar nuclei, and insulae; Right: HF without SDB (AHI = 2) with little gray matter volume loss. Sleep Problems and Brain Injury

14. Latest Version of Limb Stimulator

15. BRAIN Initiative Goals and My Research 1.Use innovative technologies/methods a.Mean Diffusivity b.Fiber Tractography c.Blood-Brain Barrier d.Arterial Spin Labeling (blood flow) 2.Integrated human brain research networks (nursing, cardiology, neurophysiology, neuroradiology, sleep specialists, bioengineering, otology, pulmonology) 3.Develop new technologies for treatment