Brain freeze induced changes in cerebral blood flow

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Abstracts / Autonomic Neuroscience: Basic and Clinical 163 (2011) 1–133

perfusion is relatively maintained during early presyncope suggesting integrity of cerebral autoregulation. A recent report however suggested that a substantial decline in cerebral oxygenation preceded both symptoms and blood pressure (BP) reduction. We therefore measured beat-to-beat finger BP, heart rate and middle cerebral artery TCD during the last 3 min of HUT induced NMS in 14 patients (11 women, age 41.1 ± 13.5). NIRS signal was derived from 2 pairs of frontal optodes and zeroed relative to values obtained one minute after initiation of HUT. Stroke volume and cardiac output were derived from finger BP using Modelflow. During presyncope BP decreased from 104/65 to 80/48 mm Hg, TCD from 96/44 to 91/ 29 cm/s, heart rate from 96 to 83 bpm, and cardiac output from 4.8 to 4.1 l/min. Changes in stroke volume were negligible (50 to 46 ml). Cerebral oxyhemoglobin decreased by 0.96 μmol whereas deoxyhemoglobin increased by 0.46 μmol. The decline in BP was clearly evident during the last 28 s of HUT accompanied by a selective decline in diastolic cerebral blood velocity and followed by a decline in heart rate. The decline in cerebral oxygenation was only evident during the last 14 s of HUT. These observations suggest that cerebral hypoperfusion during NMS is a consequence of hypotension and not due to a primary impairment of mechanisms that defend against fluctuations in systemic BP. Keywords: neurally-mediated syncope, transcranial doppler, near infrared spectroscopy

doi:10.1016/j.autneu.2011.05.165

especially at higher frequencies. Thus, it remains unclear whether CBF is regulated over a wider range of frequencies or perfusion fluctuates passively with BP fluctuations at time scales <~10 s. The goal of this study was to: 1) introduce a novel method that does not assume signal stationarity for assessment of cerebral autoregulation at multiple time scales; 2) evaluate the autoregulatory range after stroke. Methods/results: We quantified instantaneous BP–BFV relationship at multiple time scales using a novel approach adapted from multimodal pressure flow method that is based on nonlinear theory without assuming signal stationarity. Normal cerebral autoregulation is characterized by a faster recovery of the BFV than BP (larger BFV– BP phase shift). We studied 39 patients with chronic ischemic infarctions, and 40 age-matched non-stroke subjects. In control subjects, the phases of BFV oscillations were advanced compared to BP oscillations at time scales from ~2.6 to 50 s, e.g., phase shift = 54.8 ± 4.3° (SE) at 0.02–0.1 Hz and 10.7 ± 3.2° at 0.3–0.38 Hz. This finding indicates that autoregulation operates effectively over multiple time scales. The BFV–BP phase shift was consistently reduced in stroke patients (p < 0.0001) at all tested frequencies and in both hemispheres. Conclusions: CBF is regulated via complex mechanisms that operate effectively over a wide range time scales (from a few heart beats to about one minute). The alteration of multiscale CBF regulation persists after an ischemic stroke and extends into vascular territory contralateral to infarct, which may have important implications for post-stroke recovery. Keywords: stroke, cerebral autoregulation, multimodal pressure flow method

P.151 Nonlinear profile of cerebral autoregulation dynamics— Effects of stroke K. Hu (Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States — Division of Sleep Medicine, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, United States — Research Center for Adaptive Data Analysis and Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan, ROC), M.T. Lo (Division of Gerontology and Division of Interdisciplinary Medicine & Biotechnology and Margret & H.A. Rey Institute for Nonlinear Dynamics in Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States — Research Center for Adaptive Data Analysis and Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan, ROC), Y. Liu (DynaDx Corporation -Mountain View, CA, United States), C.K. Peng (Division of Interdisciplinary Medicine & Biotechnology and Margret & H.A. Rey Institute for Nonlinear Dynamics in Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States — Research Center for Adaptive Data Analysis and Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan, ROC), V. Novak (National Central University, Chungli, Taiwan, ROC — Research Center for Adaptive Data Analysis and Center for Dynamical Biomarkers and Translational Medicine, Taiwan, ROC) Background/Aims: Cerebral blood flow (CBF) is closely regulated despite changes of systemic blood pressure (BP). The time-frequency dynamics of autoregulation is important for modulation of perfusion in health, as well as for long-term recovery after stroke. Quantifying the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis (TFA) suggested that autoregulation is limited to frequencies <~0.1 Hz. However, the TFA assumes stationary signals such that the resultant BP–BFV relationship may be unreliable,

Financial support: This work was supported by National Institutes of Health Grants R01-NS045745, STTR 1R41NS053128-01A2, K99HL102241, and U01-EB008577, the KL2 Medical Research Investigator Training grant (5 KL2 RR025757-02) of Harvard Catalyst | The Harvard Clinical and Translational Science Center (Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers) (to K.H.), and American Diabetes Association Grant 1-06-CR-25 grants (to V.N.).

doi:10.1016/j.autneu.2011.05.166

P.152 Brain freeze induced changes in cerebral blood flow M.J. Falvo (War Related Illness & Injury Study Center, VA NJ Health Care System, East Orange, NJ, United States), M. Blatt (War Related Illness & Injury Study Center, VA NJ Health Care System, East Orange, NJ, United States), J.J. Jasien (War Related Illness & Injury Study Center, VA NJ Health Care System, East Orange, NJ, United States), B.M. Deegan (Electrical & Electronic Engineering, National University of Ireland Galway, Galway, Ireland), G. OLaighin (Electrical & Electronic Engineering, National University of Ireland Galway, Galway, Ireland), J.M. Serrador (War Related Illness & Injury Study Center, VA NJ Health Care System, East Orange, NJ, United States; Harvard Medical School, Boston, MA, United States; Electrical & Electronic Engineering, National University of Ireland Galway, Galway, Ireland) Ice-cream headache or ‘brain freeze’ is poorly understood, but may involve reflex activation of trigeminal pathways. As the trigeminal nerve provides primary afferent innervations to the

Abstracts / Autonomic Neuroscience: Basic and Clinical 163 (2011) 1–133

cerebral vessels, application of a cold-stimulus to the palate may induce changes in cerebral blood flow. Using transcranial Doppler, we evaluated blood flow velocity CBFV in the middle (MCA) and anterior (ACA) cerebral arteries in 14 healthy adults while consuming ambient and ice water. Blood pressure and heart rate were also recorded throughout. Subjects drink ice water through a straw placed against the upper palate and consumed as much water as possible until pain developed. MCA and ACA CBFV, heart rate, and blood pressure were analyzed before (− 7 to −2 s) pain, at the time of pain onset (+/−2 s) and after (+2 to +7 s) pain. Drinking ceased at the onset of pain. Ice water drinking durations were matched during ambient water and all data were expressed relative to a baseline period. A significant condition (ambient vs. ice) by time (before, during, after pain) interaction was observed for ACA CBFV (p = 0.029), but no significant changes were observed in MCA blood flow velocity, heart rate, or blood pressure. ACA CBFV increased slightly in both conditions prior to the development of pain. During ambient water drinking, ACA flow increased ~ 7% over baseline levels and remained elevated after drinking ceased. During ice water drinking, flow was reduced during pain and then increased slightly above baseline levels. Our results suggest the early phase of brain freeze may involve cerebral vasoconstriction, particularly in the ACA, which supports the location of endorsed pain. These results maintain a neurovascular component of brain freeze, and underscore the role of the trigeminovascular system in influencing the cerebrovasculature. Keywords: Ice-cream headache, cerebral blood flow, transcranial doppler, vasoconstriction, vasodilation Financial support: NASA, NIH. doi:10.1016/j.autneu.2011.05.167

P.153 Cerebral blood flow decreases prior to nausea during offvertical axis rotation M. Blatt (VA NJ Health Care System, East Orange, NJ -War Related Illness & Injury Study Center, United States), M.J. Falvo (VA NJ Health Care System, East Orange, NJ -War Related Illness & Injury Study Center, United States), J.J. Jasien (VA NJ Health Care System, East Orange, NJ -War Related Illness & Injury Study Center, United States), S.J. Wood (NASA Johnson Space Centre & Universities Space Research Association, Houston, TX, United States), J.M. Serrador (VA NJ Health Care System, East Orange, NJ, War Related Illness & Injury Study Center -Harvard Medical School, Boston, MA, United States) Nausea and motion sickness are uncomfortable and at times distressful symptoms often with no known cause. Understanding underlying mechanisms associated with these symptoms may lead to new treatments. The goal of this work was to determine if changes in cerebral blood flow precede the development of nausea in motion sick susceptible subjects. A total of 15 healthy subjects participated in this study. Cerebral flow velocity in the middle cerebral artery (transcranial Doppler), blood pressure (Portapres) and end-tidal CO2 were measured while subjects experienced a 20° off vertical axis rotation for 15 min at 0.1 Hz (36°/s) followed by 15 min of 0.2 Hz (72°/s) rotation. Rotation was terminated when subjects reported persistent moderate nausea or they completed 30 min. Rotation while upright did not significantly change cerebral blood flow, blood pressure or end-tidal CO2. Eleven subjects developed motion sickness and showed a significant decrease of ~ 10% (P < 0.001) in cerebral flow velocity during off vertical axis rotation compared to controls who demon-

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strated no change. Cerebral flow velocity decreased linearly until plateauing at ~289+/−34 s prior to termination of rotation due to symptoms. There was a significant increase in blood pressure compared to baseline with no difference between groups (controls: +4.9 ± 5.7 mm Hg, motion sick: + 7.9 ± 3.4 mm Hg, P < 0.001). Subjects also had a small but significant decrease in end tidal CO2 with no difference between groups (controls: −2.698 ± 2.2 mm Hg, motion sick: −3.273 ± 1.3 mm Hg, P < 0.001). These data indicate that cerebral hypoperfusion precedes the development of symptoms of motion sickness and that neither changes in blood pressure nor hypocapnia appear to be primary causes of this decrease. Further work is necessary to determine what role cerebral hypoperfusion plays in nausea and motion sickness. Keywords: motion sickness, nausea, cerebral blood flow, transcranial doppler, hypoperfusion Financial support: NASA (Serrador) and NIH (Serrador).

doi:10.1016/j.autneu.2011.05.168

P.154 Osmopressor response and lower body negative pressure induced vagal reaction Chih Cherng Lu (Tri-Service General Hospital - Anesthesiology, Taiwan ROC) Background: Blood phobia syncope is the fainting response-triggered form of the neurocardiogenic syncope. In young healthy subjects, there was a slight reduction in heart rate. Water ingestion raised peripheral sympathetic vasoconstrictor discharge in young healthy subjects. It may constitute a simple and effective prophylaxis against blood phobia syncope in healthy subjects, such as those associated with blood donation. Methods: Twelve young healthy subjects, without history of syncope underwent gravitational stress induced by lower body negative pressure chamber for 10 min or until presyncopal symptom occurred. In their initial test, participants were scheduled for either receiving 500 ml or 50 ml water drinking 15 min prior to lower body negative pressure testing in a second test on a different day. Noninvasive regional cerebral blood flow measurements using 99mTc-ethyl-cycteinate dimer (ECD) were performed after either lower body negative pressure with water or lower body negative pressure testing without water. Using SPM analysis, group comparisons were made to identify the effect of water on the alteration of cerebral blood flow. Results: Water attenuates the symptomatic scores during gravitational stress (P = 0.0047). During gravitational stress, water drinking accentuates the increase in total peripheral resistance (P = <0.05). Water ingestion increased right regional cerebral blood flow remarkably over frontal cortex and left limbic area during gravitational stress. Water elicits increment of regional cerebral blood flow over right occipital and frontal cortex, decrement of subcortical region. Lower body negative pressure decreases frontal, limbic and temporal, hypothalamus and caudate body. Conclusion: Water strongly enhances tolerance to gravitational stress. Water ingestion increased right visual and prefrontal cortex, but decrease left precentral gyrus and frontal cortex. The activation of right visual and prefrontal cortex accompanied with deactivation of left precentral gyrus and frontal cortex might mediate the neural mechanism of water to improve tolerance to lower body negative pressure.