Cerebellar Lobules Optimal Stimulation (CLOS): A Computational Pipeline to Optimize Cerebellar Lobule-Specific Electric Field Distribution

Abstract

Objective Cerebellar transcranial direct current stimulation (ctDCS) is challenging due to the complexity of the cerebellar structure which is reflected by the well-known variability in ctDCS effects. Therefore, our objective is to present a freely available computational modeling pipeline for cerebellar lobules’ optimal stimulation (CLOS). Methods CLOS can optimize lobule-specific electric field distribution following finite element analysis (FEA) using freely available computational modeling pipelines. We modeled published ctDCS montages with 5 cm × 5 cm anode placed 3 cm lateral to inion, and the same sized cathode was placed on the: (1) contralateral supra-orbital area (called Manto montage), and (2) buccinators muscle (called Celnik montage). Also, a published (3) 4×1 HD-ctDCS electrode montage was modeled. We also investigated the effects of the subject-specific head model versus Colin 27 average head model on lobule-specific electric field distribution. Three-way analysis of variance (ANOVA) was used to determine the effects of lobules, montage, and head model on the electric field distribution. The differences in lobule-specific electric field distribution across different freely available computational pipelines were also evaluated using subject-specific head model. We also presented an application of our computational pipeline to optimize a ctDCS electrode montage to deliver peak electric field at the cerebellar lobules VII-IX related to ankle function. Results Eta-squared effect size after three-way ANOVA for electric field strength was 0.05 for lobule, 0.00 for montage, 0.04 for the head model, 0.01 for lobule ∗ montage interaction, 0.01 for lobule ∗ head model interaction, and 0.00 for montage ∗ head model interaction. The electric field strength of both the Celnik and the Manto montages affected the lobules Crus I/II, VIIb, VIII, and IX of the targeted cerebellar hemisphere where Manto montage had a spillover to the contralateral cerebellar hemisphere. The 4×1 HD-ctDCS montage primarily affected the lobules Crus I/II of the targeted cerebellar hemisphere. All three published ctDCS montages were found to be not optimal for ankle function (lobules VII-IX), so we presented a novel HD-ctDCS electrode montage. Discussion Our freely available CLOS pipeline can be leveraged to optimize electromagnetic stimulation to target cerebellar lobules related to different cognitive and motor functions.

Functional near-infrared spectroscopy in conjunction with electroencephalography of cerebellar transcranial direct current stimulation responses in the latent neurovascular coupling space – a chronic stroke study

“…Table 1 lists the 12 male chronic stroke subjects (P1-P12, Mean (SD) = 46(±13) years) who participated in the current study. T1-weighted MRI was available only for the subjects P1-P6 (from All India Institute of Medical Sciences New Delhi, India) (details provided in Zeynab et al [16]). Written informed consent was obtained from each subject, and the multi-center research protocol for this study was approved by the All India Institute of Medical Sciences, New Delhi, India Institutional Review Board (IEC-129/07.04.2017), and Indian Institute of Technology Gandhinagar, India Institutional Review Board (IEC/2019-20/4/UL/046).…”

“…Computational head modeling (details provided in Zeynab et al [16]) was performed using age-appropriate averaged (n = 73) human brain MRI template for the relevant age-groups (see Table 1) that were obtained online at the https://jerlab.sc.edu/projects/neurodevelopmental-mri-database/ with the permission of Dr. John Richards. The subjects for the human brain MRI templates were all normal healthy adults with no history of neurological or psychiatric illness, head trauma with loss of consciousness, or current or past use of psycho-stimulant medications, cardiovascular disease, and no abnormal findings on the MRI [43].…”

“…The subjects for the human brain MRI templates were all normal healthy adults with no history of neurological or psychiatric illness, head trauma with loss of consciousness, or current or past use of psycho-stimulant medications, cardiovascular disease, and no abnormal findings on the MRI [43]. Neurodevelopmental MRI Database [43][44][45][46][47] consisted of average (male and female) T1-weighted MRI for the head across different age-groups as well as the segmentation priors for gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF), which was used for head modeling in CLOS pipeline [16]. The selected age-groups are as follows: (N is the number of subjects' MRI, which were used to average for that age-group), P1: 40-44 years (N=61); P2: 50-54 years (N=57); P3: 40-44 years (N=61); P4: 35-39 years (N=50); P5: 30-34 years (N=63); P6: 50-54 years (N=57); P7: 60-64 years (N=83); P8: 75-79 years (N=61); P9: 45-49 years (N=65); P10: 45-49 years (N=65); P11: 50-54 years (N=57); P12: 35-39 years (N=50).…”

“…However, TMS-based CBI Functional near-infrared spectroscopy in conjunction with electroencephalography of cerebellar transcranial direct current stimulation responses in the latent neurovascular coupling space -a chronic stroke study evaluation is time-consuming and challenging to perform in a clinical rehabilitation setting where portable neuroimaging can be investigated as a proof-of-concept [15]. Cerebellar Lobules Optimal Stimulation (CLOS) pipeline [16] was developed to investigate the cerebellar lobule-specific electric field distribution for various ctDCS montages. CLOS pipeline provided age-appropriate optimization of the ctDCS electrode montage [12] for bilateral deep ctDCS of the dentate nucleus and lower-limb representations (lobules VII-IX) [17], which was proposed to facilitate standing balance in chronic stroke survivors.…”

“…Although focal hemodynamic effects [30] in the tDCS targeted brain areas can be due to the electric field directly affecting the neurons, astrocytes, as well as the vascular cells within the NVU [31]; yet, any remote hemodynamic effects in the brain areas unaffected by the tDCS electric field can be postulated to be driven by brain connectivity [32], [33]. Briefly, neuronal activation driven by brain connectivity will be accompanied by increased cerebral blood flow and increased cerebral metabolic rate for oxygen, leading to functional hyperemia and energy supply [16]. Vascular-based functional brain imaging techniques, such as functional MRI and fNIRS, rely on this coupling to infer changes in neural activity.…”