The ubiquitous vascular response to transcranial electrical stimulation (tES) has been attributed to the secondary effect of neuronal activity forming the classic neurovascular coupling. However, the ...current density delivered transcranially concentrates in: A) the cerebrospinal fluid of subarachnoid space where cerebral vasculature resides after reaching the dural and pial surfaces and B) across the blood-brain-barrier after reaching the brain parenchyma. Therefore, it is anticipated that tES has a primary vascular influence.
Focused review of studies that demonstrated the direct vascular response to electrical stimulation and studies demonstrating evidence for tES-induced vascular effect in coupled neurovascular systems.
tES induces both primary and secondary vascular phenomena originating from four cellular elements; the first two mediating a primary vascular phenomenon mainly in the form of an immediate vasodilatory response and the latter two leading to secondary vascular effects and as parts of classic neurovascular coupling: 1) The perivascular nerves of more superficially located dural and pial arteries and medium-sized arterioles with multilayered smooth muscle cells; and 2) The endothelial lining of all vessels including microvasculature of blood-brain barrier; 3) Astrocytes; and 4) Neurons of neurovascular units.
A primary vascular effect of tES is highly suggested based on various preclinical and clinical studies. We explain how the nature of vascular response can depend on vessel anatomy (size) and physiology and be controlled by stimulation waveform. Further studies are warranted to investigate the mechanisms underlying the vascular response and its contribution to neural activity in both healthy brain and pathological conditions – recognizing many brain diseases are associated with alteration of cerebral hemodynamics and decoupling of neurovascular units.
•Transcranial electrical stimulation (tES) induces both primary and secondary vascular phenomena.•The tES-induced vascular responses originate from four cellular elements.•The perivascular nerves of pial arteries and penetrating arterioles and the endothelium of all vessels mediate a primary vascular response.•Astrocytes and neurons of neurovascular units mediate secondary vascular effects and as parts of classic neurovascular coupling.
Transcranial electric stimulation aims to stimulate the brain by applying weak electrical currents at the scalp. However, the magnitude and spatial distribution of electric fields in the human brain ...are unknown. We measured electric potentials intracranially in ten epilepsy patients and estimated electric fields across the entire brain by leveraging calibrated current-flow models. When stimulating at 2 mA, cortical electric fields reach 0.8 V/m, the lower limit of effectiveness in animal studies. When individual whole-head anatomy is considered, the predicted electric field magnitudes correlate with the recorded values in cortical (
= 0.86) and depth (
= 0.88) electrodes. Accurate models require adjustment of tissue conductivity values reported in the literature, but accuracy is not improved when incorporating white matter anisotropy or different skull compartments. This is the first study to validate and calibrate current-flow models with
intracranial recordings in humans, providing a solid foundation to target stimulation and interpret clinical trials.
Transcranial Direct Current Stimulation (tDCS) is investigated for a broad range of neuropsychiatric indications, various rehabilitation applications, and to modulate cognitive performance in diverse ...tasks. Specificity of tDCS refers broadly to the ability of tDCS to produce precise, as opposed to diffuse, changes in brain function. Practically, specificity of tDCS implies application-specific customization of protocols to maximize desired outcomes and minimize undesired effects. Especially given the simplicity of tDCS and the complexity of brain function, understanding the mechanisms leading to specificity is fundamental to the rational advancement of tDCS. We define the origins of specificity based on anatomical and functional factors. Anatomical specificity derives from guiding current to targeted brain structures. Functional specificity may derive from either activity-selectivity, where active neuronal networks are preferentially modulated by tDCS, or input-selectivity, where bias is applied to different synaptic inputs. Rational advancement of tDCS may require leveraging all forms of specificity.
During transcranial electrical stimulation (tES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), current density concentration ...around the electrode edges that is predicted by simplistic skin models does not match experimental observations of erythema, heating, or other adverse events. We hypothesized that enhancing models to include skin anatomical details, would alter predicted current patterns to align with experimental observations.
We develop a high-resolution multi-layer skin model (epidermis, dermis, and fat), with or without additional ultra-structures (hair follicles, sweat glands, and blood vessels). Current flow patterns across each layer and within ultra-structures were predicted using finite element methods considering a broad range of modeled tissue parameters including 78 combinations of skin layer conductivities (S m
): epidermis (standard: 1.05 × 10
; range: 1.05 × 10
to 0.465); dermis (standard: 0.23; range: 0.0023 to 23), fat (standard: 2 × 10
; range: 0.02 to 2 × 10
). The impact of each ultra-structures in isolation and combination was evaluated with varied basic geometries. An integrated final model is then developed.
Consistent with prior models, current flow through homogenous skin was annular (concentrated at the electrode edges). In multi-layer skin, reducing epidermis conductivity and/or increasing dermis conductivity decreased current near electrode edges, however no realistic tissue layer parameters produced non-annular current flow at both epidermis and dermis. Addition of just hair follicles, sweat glands, or blood vessels resulted in current peaks around each ultrastructure, irrespective of proximity to electrode edges. Addition of only sweat glands was the most effective approach in reducing overall current concentration near electrode edges. Representation of blood vessels resulted in a uniform current flow across the vascular network. Finally, we ran the first realistic model of current flow across the skin.
We confirm prior models exhibiting current concentration near hair follicles or sweat glands, but also exhibit that an overall annular pattern of current flow remains for realistic tissue parameters. We model skin blood vessels for the first time and show that this robustly distributes current across the vascular network, consistent with experimental erythema patterns. Only a state-of-the-art precise model of skin current flow predicts lack of current concentration near electrode edges across all skin layers.
Objective. Research in the area of transcranial electrical stimulation (TES) often relies on computational models of current flow in the brain. Models are built based on magnetic resonance images ...(MRI) of the human head to capture detailed individual anatomy. To simulate current flow on an individual, the subject's MRI is segmented, virtual electrodes are placed on this anatomical model, the volume is tessellated into a mesh, and a finite element model (FEM) is solved numerically to estimate the current flow. Various software tools are available for each of these steps, as well as processing pipelines that connect these tools for automated or semi-automated processing. The goal of the present tool-realistic volumetric-approach to simulate transcranial electric simulation (ROAST)-is to provide an end-to-end pipeline that can automatically process individual heads with realistic volumetric anatomy leveraging open-source software and custom scripts to improve segmentation and execute electrode placement. Approach. ROAST combines the segmentation algorithm of SPM12, a Matlab script for touch-up and automatic electrode placement, the finite element mesher iso2mesh and the solver getDP. We compared its performance with commercial FEM software, and SimNIBS, a well-established open-source modeling pipeline. Main results. The electric fields estimated with ROAST differ little from the results obtained with commercial meshing and FEM solving software. We also do not find large differences between the various automated segmentation methods used by ROAST and SimNIBS. We do find bigger differences when volumetric segmentation are converted into surfaces in SimNIBS. However, evaluation on intracranial recordings from human subjects suggests that ROAST and SimNIBS are not significantly different in predicting field distribution, provided that users have detailed knowledge of SimNIBS. Significance. We hope that the detailed comparisons presented here of various choices in this modeling pipeline can provide guidance for future tool development. We released ROAST as an open-source, easy-to-install and fully-automated pipeline for individualized TES modeling.
Background:
Fatigue is a common and debilitating feature of multiple sclerosis (MS) that remains without reliably effective treatment. Transcranial direct current stimulation (tDCS) is a promising ...option for fatigue reduction. We developed a telerehabilitation protocol that delivers tDCS to participants at home using specially designed equipment and real-time supervision (remotely supervised transcranial direct current stimulation (RS-tDCS)).
Objective:
To evaluate whether tDCS can reduce fatigue in individuals with MS.
Methods:
Dorsolateral prefrontal cortex left anodal tDCS was administered using a RS-tDCS protocol, paired with 20 minutes of cognitive training. Here, two studies are considered. Study 1 delivered 10 open-label tDCS treatments (1.5 mA; n = 15) compared to a cognitive training only condition (n = 20). Study 2 was a randomized trial of active (2.0 mA, n = 15) or sham (n = 12) delivered for 20 sessions. Fatigue was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS)—Fatigue Short Form.
Results and conclusion:
In Study 1, there was modest fatigue reduction in the active group (−2.5 ± 7.4 vs −0.2 ± 5.3, p = 0.30, Cohen’s d = −0.35). However, in Study 2 there was statistically significant reduction for the active group (−5.6 ± 8.9 vs 0.9 ± 1.9, p = 0.02, Cohen’s d = −0.71). tDCS is a potential treatment for MS-related fatigue.
Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS ...are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4×1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4×1 montage (4× cathode, surrounding a single central anode; montage radius ~3cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4×1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject.
We provide direct evidence in humans that TES with a 4×1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4×1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4×1-Ring montage for cortically targeted neuromodulation.
► Experimental transcranial electrical stimulation validates MRI-derived model of brain current delivery. ► High-Definition tDCS focally delivers current to motor cortex. ► Both TES and tDCS produce inward (normal) currents beneath the anode. ► The High-Definition electrode montage could be used for focal therapeutic tDCS.
Highlights • tDCS is thought to alter cognition through cortical excitability shifts, with anodal and cathodal stimulation producing opposite effects. • Here we show that DCS facilitates LTP and ...diminishes LTD in hippocampal slices. • These effects can be polarity independent, as both anodal and cathodal DCS can produce similar effects. • Outcomes depended on dendritic location and endogenous synaptic activity, motivating a more nuanced approach to tDCS that considers these factors.
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