E015 Neural correlates of cardiorespiratory activities in presymptomatic Huntington’s disease

<h3>Background</h3> Autonomic dysfunction has been described in Huntington’s disease (HD);^1–6 however, little is known about its neural underpinnings. <h3>Aims</h3> We evaluated the integrity of the neural circuitry involving cardiac and respiratory functions in gene-positive pre-symptomatic individuals (PHD), by determining the correlations of spontaneous cerebral hemodynamic fluctuations with variations in heart rate (HR) and breath-by-breath oxygen-carbon dioxide exchange ratio (bER). <h3>Methods</h3> Eighteen PHD and 22 healthy participants (HC) were included. Procedures were approved by the Institutional Review Board at Massachusetts General Hospital and signed informed consent was obtained from participants. MRI brain scanning was performed on a 3-Tesla scanner. Blood oxygen-level dependent (BOLD) images were acquired at rest (TR=1250ms,TE=30ms,voxel size=2.3×2.3×2.4 mm,duration=10 minutes), with simultaneous measurements of partial pressures of carbon dioxide and oxygen, and heart rate (HR). The time series of HR and bER were correlated with BOLD signal changes (ΔBOLD) using a Hilbert transform analysis, as described previously.⁷ Voxel-level multivariate regression models were constructed to compare the brain maps of HR-ΔBOLD and bER-ΔBOLD correlations by group (PHD vs HC) with age as a covariate. <h3>Results</h3> Both HR-ΔBOLD and bER-ΔBOLD correlations were smaller in several brain/brainstem regions in PHD than HC (figure 1). <h3>Conclusion</h3> Our results suggest that dysfunction of the neural circuitry responsible for cardiac and respiratory functions, may underlie early autonomic dysfunction in HD. <h3>References</h3> Schultz JL, Harshman LA, Kamholz JA, Nopoulos PC. <i>Auton Neurosci</i> 2021;<b>231</b>:102775. Kobal J, Melik Z, Cankar K, Strucl M. <i>J Neurol</i> 2014;<b>261</b>:1119–1125. Assante R, Salvatore E, Nappi C, <i>et al. J Nucl Cardiol</i> 2022;<b>29</b>:642–648. Fischer J, Oepen G, Matthys H. <i>Biological Psychology</i> 1983;<b>16</b>:286. Leopold NA, Kagel MC, Berkowitz L, Stafford S.<i> J Neurol</i> 1985;<b>232</b>:87. Morton AJ. Exp Neurol 2013;<b>243</b>:34–44. Chan ST, Evans KC, Song TY, <i>et al. PLoS One</i> 2020;<b>15</b>:e0238946.