Neurovascular coupling during deep brain stimulation

Abstract

a b s t r a c tBackground: Deep brain stimulation (DBS) is an effective treatment for movement disorders, yet its mechanisms of action remain unclear. One method used to study its circuit-wide neuromodulatory effects is functional magnetic resonance imaging (fMRI) which measures hemodynamics as a proxy of neural activity. To interpret functional imaging data, we must understand the relationship between neural and vascular responses, which has never been studied with the high frequencies used for DBS. Objective: To measure neurovascular coupling in the rat motor cortex during thalamic DBS. Method: Simultaneous intrinsic optical imaging and extracellular electrophysiology was performed in the motor cortex of urethane-anesthetized rats during thalamic DBS at 7 different frequencies. We related Maximum Change in Reflectance (MCR) from the imaging data to Integrated Evoked Potential (IEP) and change in broadband power of multi-unit (MU) activity, computing Spearman's correlation to determine the strength of these relationships. To determine the source of these effects, we studied the contributions of antidromic versus orthodromic activation in motor cortex perfusion using synaptic blockers. Results: MCR, IEP and change in MU power increased linearly to 60 Hz and saturated at higher frequencies of stimulation. Blocking orthodromic transmission only reduced the DBS-induced change in optical signal by~25%, suggesting that activation of corticofugal fibers have a major contribution in thalamic-induced cortical activation. Conclusion: DBS-evoked vascular response is related to both evoked field potentials as well as multi-unit activity.

Monitoring stimulus‐evoked hemodynamic response during deep brain stimulation with single fiber spectroscopy

“…In response to DBS, our data consistently indicated an increase in blood volume fraction, which is aligned with our previous findings using a camera-based spectral imaging system [19,20]. However, oxygen saturation was inconsistent in the deep layer and showed both increases and decreases compared to the baseline.…”

“…Recently, multiple groups have explored optical tools for surgical guidance and investigated the DBS-induced hemodynamic response in animal models and in human patients. Our group has previously used a camera-based spectral imaging system to study cortical perfusion (i.e., blood volume fraction) [19] and neurovascular coupling [20] during thalamic DBS. Neurovascular coupling refers to the relationship between neural activities and the subsequent changes in hemodynamics.…”

Multi-scale neural decoding and analysis

“…For this reason, many fMRI-spike and PET-spike studies are performed on anesthetized animals (e.g. [225,[227][228][229][230]), although some studies utilize specialized MR-compatible restraint systems to limit movement during imaging (e.g. [223,231]).…”

Non-linear frequency-dependence of neurovascular coupling in the cerebellar cortex implies vasodilation-vasoconstriction competition

“…Generally, the stimulus-evoked changes in CBF (or related parameters) linearly correlate with NA at increasing activation rates. Non-linearities have been reported mainly as a ceiling-effect due to a saturation of CBF increase at certain frequencies or stimulus amplitudes 28-30, 37, 38 , usually with increasing perfusion at increasing frequencies. Interestingly, few cases have been reported of perfusion decreasing at higher frequencies, well explained by the corresponding decrease of ∑LFP 33, 36 .…”