The effects of intracranial stimulation on local neurovascular responses in humans

Background Deep brain stimulation (DBS) is used to treat neurological and psychiatric disorders by modulating neuronal circuits. However, other mechanisms of DBS, such as the effects of electrical stimulation on the neurovascular unit remain poorly understood due to limitations of capturing microvascular changes near implanted leads. This motivated us to investigate electrophysiological surrogates of vascular dynamics in response to intraoperative microstimulation. Methods Microelectrode recordings (n = 193; 108 patients) were obtained during DBS implantation surgery from two electrodes (∼600 µm apart) before and after microstimulation through one electrode. Linear mixed models assessed cardioballistic waveform (CBW) amplitude changes following low-frequency (LFS, 1 Hz) or high-frequency stimulation (HFS, 100 Hz), with comparisons across basal ganglia regions and in white matter. An analytical model interpreted CBW amplitudes as pressure-driven vessel wall expansion, enabling estimation of stimulation-evoked vasodilation and cerebral blood flow. Results CBW amplitudes increased significantly after HFS at the stimulating electrode, but not at the non-stimulating electrode or after LFS. Significant region-specific effects were observed in the ventral intermediate nucleus (Vim; 107 ± 13%), subthalamic nucleus (STN; 79 ± 7%), and globus pallidus internus (GPi; 78 ± 8%), but not in white matter (50 ± 14%) or substantia nigra (45 ± 8%). Modelling showed that the mean 88% CBW increase across Vim, STN, and GPi corresponds to an acute increase in cerebral blood flow. Conclusion Intracranial CBW recordings reveal that high-frequency DBS evokes region-specific vascular responses which can be modelled as substantial increases in local blood flow, establishing CBW amplitude as a novel biomarker of subcortical hemodynamics, and a potential therapeutic modality.