Neurovascular coupling methods in healthy individuals using transcranial doppler ultrasonography: A systematic review and consensus agreement

Neurovascular coupling (NVC) is the perturbation of cerebral blood flow (CBF) to meet varying metabolic demands induced by various levels of neural activity. NVC may be assessed by Transcranial Doppler ultrasonography (TCD), using task activation protocols, but with significant methodological heterogeneity between studies, hindering cross-study comparisons. Therefore, this review aimed to summarise and compare available methods for TCD-based healthy NVC assessments. Medline (Ovid), Scopus, Web of Science, EMBASE (Ovid) and CINAHL were searched using a predefined search strategy (PROSPERO: CRD42019153228), generating 6006 articles. Included studies contained TCD-based assessments of NVC in healthy adults. Study quality was assessed using a checklist, and findings were synthesised narratively. 76 studies (2697 participants) met the review criteria. There was significant heterogeneity in the participant position used (e.g., seated vs supine), in TCD equipment, and vessel insonated (e.g. middle, posterior, and anterior cerebral arteries). Larger, more significant, TCD-based NVC responses typically included a seated position, baseline durations >one-minute, extraneous light control, and implementation of previously validated protocols. In addition, complementary, combined position, vessel insonated and stimulation type protocols were associated with more significant NVC results. Recommendations are detailed here, but further investigation is required in patient populations, for further optimisation of TCD-based NVC assessments.