Significant group-level hotspots found in deep brain regions during transcranial direct current stimulation (tDCS): A computational analysis of electric fields
Introduction
Transcranial direct current stimulation (tDCS) is a form of brain stimulation that modulates brain activity (Nitsche and Paulus, 2000, Priori et al., 1998). Modulation is achieved by the delivery of a small electric current (1–2 mA) to the brain via bipolar electrodes placed on the scalp. Different montages targeting the motor cortex (C3/C4 position of the 10–20 electroencephalogram system to target M1), the dorsolateral prefrontal cortex (F3/F4 to target DLPFC), or the primary visual cortex (Oz to target V1) have been used to treat pain and depression (Antal et al., 2011, Boggio et al., 2009, Brunoni et al., 2013, DaSilva et al., 2015, DaSilva et al., 2012, Hagenacker et al., 2014, Hansen et al., 2011, Palm et al., 2012, Riberto et al., 2011, Valle et al., 2009, Weber et al., 2014). The modulation effects produced by tDCS are hypothesized to derive from a combination of different mechanisms: a shift in membrane potential and synaptic strength mediated in a polarity-dependent manner (Antonenko et al., 2019, Laakso et al., 2019, Miranda et al., 2013, Opitz et al., 2015), in which the tDCS-generated electric field (EF) is the primary determinant. Neuromodulation is not restricted to only underlying cortical networks near the electrodes, owing to a stronger EF (Jang et al., 2009, Kim et al., 2012). Indirect neuromodulation of the deep region may be possible through associated cortical networks (e.g., basal ganglia or cingulate cortex) (Frase et al., 2016, Keeser et al., 2011). Moreover, direct modulation of deep brain targets may be possible due to the large spread of the injected current flowing between the two electrodes (Csifcsák et al., 2018, DaSilva et al., 2015, DaSilva et al., 2012, Huang and Parra, 2019, Polanía et al., 2012). Indeed, modulation of blood flow changes in deep brain regions supports the hypothesis that tDCS can affect brain activity not only in the cortical region but also in deeper regions (Chib et al., 2013, Weber et al., 2014). Experimental verification of tDCS-generated EFs in subcortical, subthalamic, and hippocampus regions has been reported (Chhatbar et al., 2018, Huang et al., 2017, Vöröslakos et al., 2018). However, verification of the existence of consistent hotspots in specific deep brain regions with sufficient resolution, quantification, or reliability using only an experimental approach is difficult to consider the questions raised in this work.
The tDCS-generated EF in the brain tissues during tDCS has been highly debated in literature in the last 10 years using computational approaches (Bikson et al., 2013, Datta et al., 2009, Gomez-Tames et al., 2016, Guler et al., 2016, Huang et al., 2013, Miranda et al., 2006, Nitsche et al., 2008, Ramaraju et al., 2018, Truong et al., 2013). Human head models that account for anatomical features of the individual have been developed (Datta et al., 2012, Datta et al., 2011, Huang and Parra, 2015, Kessler et al., 2013, Laakso et al., 2015, Opitz et al., 2015, Rashed et al., 2019a, Rashed et al., 2019b). EF hotspots have been found in deeper brain regions related to pain perception and analgesia in a specific subject (Csifcsák et al., 2018, Gomez-Tames et al., 2019a, Laakso et al., 2016, Laakso et al., 2015). To confirm consistent hotspots in deep regions, analysis of tDCS-generated EFs at the group-level is urged in deep brain regions. The group level analysis uses registration methods that can map the EFs from individual cortical regions to EFs on a standard space but only implemented to the cortical or cerebellar region.
The primary goal of the present study was to evaluate the strength of the internal EF in targeted deeper brain regions at a group level while considering tDCS montages for the potential treatment of migraine, pain, or depression. High-resolution computational models with registration techniques were used for post-processing analysis at group level EF of the deeper brain regions for the first time.
Section snippets
Head models
The head models of 18 subjects were constructed from magnetic resonance images (MRIs) (available at http://hdl.handle.net/1926/1687) and represented by a grid of cubic voxels (an average of 40 × 106 voxels with a resolution of 0.5 mm). The mean age of the sample population was 43.4 ± 9.8 years (all males). The tissue compartments were segmented into the following tissues and body fluids: skin, fat, muscle, blood, bone (cancellous and cortical), gray matter, white matter, cerebellum gray matter,
Interindividual differences and registration
Fig. 3 shows that the effect of individual variability on the spatial distribution of the EF in deep brain tissues is significant for the exemplary electrode montage C3-Fp2. For instance, the left side of the caudate or putamen was preferentially beyond the threshold in some subjects but was observed at both sides in other subjects. Additionally, a 14% variability in peak EF values was found among the subjects (relative standard deviation). The individual EFs of the deep brain regions were
Discussion
tDCS studies have shown a potential benefit in using tDCS in the treatment of pain disorders and depression in which relief circuity may lie in deeper brain regions (DaSilva et al., 2012, Thibaut et al., 2017, Vaseghi et al., 2014). In this study, we computationally revealed that a tDCS-generated EF was not restricted to the target region below the electrodes and that significant group-level hotspots appeared in deep brain regions (Fig. 4).
EF peaks had a 70% of the maximum cortical EF in the
Conclusions
The influence of tDCS is usually focused on the cortex while the effects of currents reaching deep brain structures are neglected. This study showed that consistent tDCS-generated hotspots appeared in deeper brain regions and that a particular selected montage can facilitate the targeting of specific regions for neurological applications. Moreover, this study demonstrated that the EF dosage from tDCS at some deeper brain regions is comparable to that at cortical regions thereby lending credence
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
This work was supported by a Grant-in-Aid for Scientific Research (A) (JSPS KAKENHI 17H00869) and a Grant-in-Aid for Early-Career Scientists (JSPS KAKENHI 19K20668) from the Japanese Society for the Promotion of Science (JSPS).
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