Abstract.SignificanceCombining diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS) permits simultaneous monitoring of multiple cerebral hemodynamic parameters related to cerebral autoregulation; however, interpreting these optical measurements can be confounded by signal contamination from extracerebral tissue.AimWe aimed to evaluate extracerebral signal contamination in NIRS/DCS data acquired during transient hypotension and assess suitable means of separating scalp and brain signals.ApproachA hybrid time-resolved NIRS/multidistance DCS system was used to simultaneously acquire cerebral oxygenation and blood flow data during transient orthostatic hypotension induced by rapid-onset lower body negative pressure (LBNP) in nine young, healthy adults. Changes in microvascular flow were verified against changes in middle cerebral artery velocity (MCAv) measured by transcranial Doppler ultrasound.ResultsLBNP significantly decreased arterial blood pressure (−18%±14%), scalp blood flow (>30%), and scalp tissue oxygenation (allp≤0.04versus baseline). However, implementing depth-sensitive techniques for both DCS and time-resolved NIRS indicated that LBNP did not significantly alter microvascular cerebral blood flow and oxygenation relative to their baseline values (allp≥0.14). In agreement, there was no significant reduction in MCAv (8%±16%;p=0.09).ConclusionTransient hypotension caused significantly larger blood flow and oxygenation changes in the extracerebral tissue compared to the brain. We demonstrate the importance of accounting for extracerebral signal contamination within optical measures of cerebral hemodynamics during physiological paradigms designed to test cerebral autoregulation.