Transcranial electrical stimulation effects on neurovascular coupling

Abstract

Transcranial electrical stimulation (tES) can exert cerebrovascular effects, but the mechanisms are unclear. Long-term (≥3min) transcranial direct current stimulation (tDCS) can also change the extracellular ion concentrations that can modulate neuronal excitability. An increase in interstitial K+ can modulate the neurovascular system's sensitivity via Kir channels in the astrocytes and the mural cells.To gain a mechanistic understanding of the tES effects on neurovascular coupling (NVC), we used a physiologically constrained multi-compartmental model (having nested pathways) for modal analysis to study the dynamic properties of the system for the output changes in blood vessel circumference and their natural frequencies in the frequency domain. Then, we used the open-source rsHRF toolbox and the functional magnetic resonance imaging (fMRI)-tDCS dataset to show the effects of anodal tDCS on hemodynamic response function (HRF) in the grey matter and at three regions of interest in the grey matter underlying anodal electrode (FC5), cathodal electrode (FP2), and an independent site remote from the electrodes (PZ). A canonical HRF model and a Finite Impulse Response (FIR) model captured the anodal tDCS effects on the temporal profile of the HRF. The modal analysis characterized the tES's vascular effects through neuronal and non-neuronal pathways, where stable modes were found for the smooth muscle cell compartment in the 0Hz-0.05Hz range.Our study showed tDCS onset effects on the neurovascular coupling (and HRF) for verum and sham tDCS conditions that were different from the no tDCS condition, which questions the validity of the placebo. Therefore, it is crucial to avoid fitting a common HRF for the whole brain, and disentangling the tES effect on the HRF is critical to the fMRI-tES studies. Future studies also need to address the trade-off between bias (in canonical HRF) and variance (in FIR HRF) that can be achieved by applying a mechanistic grey-box model.

Applications of open-source software ROAST in clinical studies: A review

“…In addition, many studies run the models on the example head included with ROAST or an individual sample from the investigators. These work cover various clinical applications including: attention-deficit hyperactivity disorder [ 61 , 62 ], aging [ 63 ], associative memory [ 64 , 65 ], attention [ 66 – 68 ], body awareness [ 69 ], cognitive control and function [ 70 ]; Fusco et al [ 125 ]; [ 71 , 72 ], connectivity [ 73 ], decision making [ 74 – 77 ]; Schulreich and Schwabe [ 126 ], declarative learning [ 78 ], depressive disorder [ 79 ], electroencephalography (EEG) research [ 80 – 83 ], imitation [ 84 ], memory retrieval [ 85 – 87 ], mind wandering [ 88 , 89 ], motor learning [ 90 – 95 ], motor skills [ 96 – 98 ], neurorehabilitation [ 60 ], neurovascular coupling [ 99 ], obsessive-compulsive disorder [ 100 ], phantom limb pain [ 101 ], post-anoxic leukoencephalopathy [ 102 ], reading speed [ 103 ], schizophrenia [ 104 ], social anxiety disorder [ 105 ], stroke [ 106 ], visual perception [ 107 , 108 ], and working memory [ 109 – 115 ].…”

Brain-behavior analysis of transcranial direct current stimulation effects on a complex surgical motor task

“…of the cerebral surface area and the cerebellar gray matter volume (Buckner et al, 2011), which needs future investigation based on fNIRS directed functional connectivity (specifically, subserved by the ventral superior longitudinal fascicle SLF III (Kamat et al, 2022b)) vis-à-vis error-related perception action coupling. Also, tDCS effects on the extraneuronal milieu in neurovascular unit (Arora and Dutta, 2022) needs investigation where a POS-PRE decrease in the left prefrontal scalp EEG activity (within 1-40Hz and 1-5sec at the start of the FLS task) was found to be related to an increase in the left prefrontal HbO cortical activation (from 5-15sec) see Figures 5f and 6a. Notably, the left prefrontal scalp ERSP changes were partly driven by the EEG frequencies below 8Hz (e.g., theta activity) as seen in the Figures 5e and 5g.…”

Inconsistencies in mapping current distribution in transcranial direct current stimulation

“…It may also be possible that the intra-subject variability in the current distribution maps is in part due to the current-induced hemodynamic effects in the brain. Previous studies have shown that transcranial electrical simulation can evoke transient changes in the cerebral blood flow and blood volume (Zheng et al, 2011 ; Arora et al, 2021 ; Arora and Dutta, 2022b ), which could in turn affect the current path by altering the overall conductivity of the neurovascular tissue.…”