Deep Cerebellar Transcranial Direct Current Stimulation of the Dentate Nucleus to Facilitate Standing Balance in Chronic Stroke Survivors—A Pilot Study

Abstract

Objective: Cerebrovascular accidents are the second leading cause of death and the third leading cause of disability worldwide. We hypothesized that cerebellar transcranial direct current stimulation (ctDCS) of the dentate nuclei and the lower-limb representations in the cerebellum can improve functional reach during standing balance in chronic (>6 months’ post-stroke) stroke survivors. Materials and Methods: Magnetic resonance imaging (MRI) based subject-specific electric field was computed across a convenience sample of 10 male chronic (>6 months) stroke survivors and one healthy MRI template to find an optimal bipolar bilateral ctDCS montage to target dentate nuclei and lower-limb representations (lobules VII–IX). Then, in a repeated-measure crossover study on a subset of 5 stroke survivors, we compared 15 min of 2 mA ctDCS based on the effects on successful functional reach (%) during standing balance task. Three-way ANOVA investigated the factors of interest– brain regions, montages, stroke participants, and their interactions. Results: “One-size-fits-all” bipolar ctDCS montage for the clinical study was found to be PO9h–PO10h for dentate nuclei and Exx7–Exx8 for lobules VII–IX with the contralesional anode. PO9h–PO10h ctDCS performed significantly (alpha = 0.05) better in facilitating successful functional reach (%) when compared to Exx7–Exx8 ctDCS. Furthermore, a linear relationship between successful functional reach (%) and electric field strength was found where PO9h–PO10h montage resulted in a significantly (alpha = 0.05) higher electric field strength when compared to Exx7–Exx8 montage for the same 2 mA current. Conclusion: We presented a rational neuroimaging based approach to optimize deep ctDCS of the dentate nuclei and lower limb representations in the cerebellum for post-stroke balance rehabilitation. However, this promising pilot study was limited by “one-size-fits-all” bipolar ctDCS montage as well as a small sample size.

Microneurosurgical techniques and perioperative strategies utilized to optimize experimental supracollicular decerebration in rats

“…Neurosurgeons have extensively and variably utilized transcranial magnetic and deep brain stimulation of the motor cortex (Pagni et al, 2008), internal capsule (Franzini et al, 2008), thalamus (Yang et al, 2020), globus pallidus internus (Tan et al, 2016), subthalamic nucleus (Lin et al, 2020a;Tan et al, 2016;Vassal et al, 2019), pedunculopontine nucleus (Lin et al, 2020b), and cerebellum (Bologna and Beradrelli, 2018;Franҫa et al, 2018;Okromelidze et al, 2020;Rezaee et al, 2020) to ameliorate Parkinsonian tremor, rigidity, and bradykinesia (Lin et al, 2020a;Pagni et al, 2008;Tan et al, 2016;Vassal et al, 2019), essential tremor (Blaabjerg et al, 2020), and dystonia (Okromelidze et al, 2020;Pagni et al, 2008). Studies suggest, by extrapolative deduction, the putative efficacy of such techniques in relieving spasticity (Franzini et al, 2008;Pagni et al, 2008;Rezaee et al, 2020;Vassal et al, 2019). We may therapeutically enhance and amplify the activity and discharge of brainstem GABAergic and glycinergic reticulospinal neurons in human patients through electrical stimulation or by administering pharmacological agonists of specific receptor subtypes parenterally, epidurally, intraventricularly (via a surgically placed Ommaya reservoir), or locally microiontophoretically.…”

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

“…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. We first investigated the effects of ctDCS on CBI in healthy humans based on computational modeling of the electric field distribution in the cerebellum as well as neurophysiological testing [18].…”

“…This variability in the recruitment was postulated due to diverse effects on different cerebellar cell populations; therefore, we optimized the lobule-specific electric field distribution using CLOS for deep ctDCS of the dentate nucleus and the lower-limb representations in the cerebellum. Deep ctDCS was proposed to facilitate standing balance function during a challenging functional reach task [17] using a low-cost adaptive balance training platform [19]. Besides the cortical route, brainstem structures can also be involved since direct electrical stimulation of the cerebellum led to focal (single-joint) ipsilateral movements at the head (vermal lobule VI), face/mouth (hemispheric lobule VI), and lower-limb (hemispheric lobules VIIb-IX) [20].…”

“…Based on the prior fMRI works [24], we postulated that ctDCS of the cerebellar hemispheric lobules Crus I-Crus II (in functional gradient 1, [24], [26]), the dentate nucleus, and the hemispheric lobules VIIb-IX (in functional gradient 2, [24], [26]) should modulate cerebrum activity differently during the standing balance reach task [17] that can be measured with portable neuroimaging including functional near-infrared spectroscopy (fNIRS) in conjunction with electroencephalography (EEG) [27], [28], [29]. Simultaneous fNIRS-EEG data can be used to estimate the state of the neurovascular coupling based on the tDCSevoked responses [28], [27].…”

“…We also investigated the sensorimotor cortex (SMC) (Broadmann Areas 1, 2, 3, and 4) activation that is characterized by the sensorimotor rhythm, typically at a frequency of [8][9][10][11][12][13] Hz, that can be affected with ctDCS [39]. Our prior works have shown that different ctDCS electrode montages affect different parts of the cerebellum [7,21, including effects on the standing balance performance in chronic stroke survivors using a Generalized Linear Model [17]; however portable neuroimaging of the ctDCS response was not presented vis-àvis lobule-specific electric field. In this proof-of-concept study, we evaluated the feasibility of fNIRS-EEG joint-imaging in the chronic stroke survivors (without cerebellar lesion) at the point of care in low-resource settings [17].…”