Cerebellar transcranial direct current stimulation interacts with BDNF Val66Met in motor learning

Vliet, Rick van der; Jonker, Zeb D.; Louwen, Suzanne; Heuvelman, Marco; Vreede, Linda de; Ribbers, Gerard M.; Zeeuw, Chris I. De; Donchin, Opher; Selles, Ruud W.; Geest, Jos N. van der; Frens, Maarten A.

doi:10.1016/j.brs.2018.04.009

Cited by 15 publications

(12 citation statements)

References 86 publications

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“…Hence, the modulation of the silence period may directly impact the conditioned responses. This is consistent with earlier studies investigating the impact of tDCS on motor learning [ 83 – 86 ] and suggests that the facilitation of the conditioned eyeblink response, which has been reported under anodal tDCS [ 83 , 84 ], may be associated with a reduction in the silence period following complex spikes.…”

Section: Discussionsupporting

confidence: 92%

Transcranial direct current stimulation of cerebellum alters spiking precision in cerebellar cortex: A modeling study of cellular responses

Hancock

Santaniello

2021

PLoS Comput Biol

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Transcranial direct current stimulation (tDCS) of the cerebellum has rapidly raised interest but the effects of tDCS on cerebellar neurons remain unclear. Assessing the cellular response to tDCS is challenging because of the uneven, highly stratified cytoarchitecture of the cerebellum, within which cellular morphologies, physiological properties, and function vary largely across several types of neurons. In this study, we combine MRI-based segmentation of the cerebellum and a finite element model of the tDCS-induced electric field (EF) inside the cerebellum to determine the field imposed on the cerebellar neurons throughout the region. We then pair the EF with multicompartment models of the Purkinje cell (PC), deep cerebellar neuron (DCN), and granule cell (GrC) and quantify the acute response of these neurons under various orientations, physiological conditions, and sequences of presynaptic stimuli. We show that cerebellar tDCS significantly modulates the postsynaptic spiking precision of the PC, which is expressed as a change in the spike count and timing in response to presynaptic stimuli. tDCS has modest effects, instead, on the PC tonic firing at rest and on the postsynaptic activity of DCN and GrC. In Purkinje cells, anodal tDCS shortens the repolarization phase following complex spikes (-14.7 ± 6.5% of baseline value, mean ± S.D.; max: -22.7%) and promotes burstiness with longer bursts compared to resting conditions. Cathodal tDCS, instead, promotes irregular spiking by enhancing somatic excitability and significantly prolongs the repolarization after complex spikes compared to baseline (+37.0 ± 28.9%, mean ± S.D.; max: +84.3%). tDCS-induced changes to the repolarization phase and firing pattern exceed 10% of the baseline values in Purkinje cells covering up to 20% of the cerebellar cortex, with the effects being distributed along the EF direction and concentrated in the area under the electrode over the cerebellum. Altogether, the acute effects of tDCS on cerebellum mainly focus on Purkinje cells and modulate the precision of the response to synaptic stimuli, thus having the largest impact when the cerebellar cortex is active. Since the spatiotemporal precision of the PC spiking is critical to learning and coordination, our results suggest cerebellar tDCS as a viable therapeutic option for disorders involving cerebellar hyperactivity such as ataxia.

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Section: Discussionsupporting

confidence: 92%

Transcranial direct current stimulation of cerebellum alters spiking precision in cerebellar cortex: A modeling study of cellular responses

Hancock

Santaniello

2021

PLoS Comput Biol

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“…The BDNF Val66Met polymorphism is thought to be associated with slowed motor skill learning due to altered long-term potentiation conditions [ 12 , 26 ]. Van der Vliet and colleagues found susceptibility of non-carriers to anodal tDCS in eyeblink conditioning [ 43 ]. Finally, effect sizes of cerebellar tDCS may be much smaller than initially thought, and consistent tDCS effects may only be picked up in very large study populations [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Lack of cerebellar tDCS effects on learning of a complex whole body dynamic balance task in middle-aged (50–65 years) adults

Rauscher

Yavari

Batsikadze

et al. 2020

Neurol. Res. Pract.

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Background Cerebellar transcranial direct current stimulation (tDCS) is widely considered as a promising non-invasive tool to foster motor performance and learning in health and disease. The results of previous studies, however, are inconsistent. Our group failed to provide evidence for an effect of cerebellar tDCS on learning of a complex whole body dynamic balance task in young and healthy participants. Ceiling effects in the young study population are one possible explanation for the negative findings. Methods In the present study, we therefore tested 40 middle-aged healthy participants between the ages of 50 to 65 years. Participants received either anodal or sham cerebellar tDCS using a double-blinded study design while performing a balance task on a Lafayette Instrument 16,030 stability platform®. Mean platform angle and mean balance time were assessed as outcome measures. Results Significant learning effects were found in all participants. Balancing performance and learning rate was significantly less in the group of middle-aged adults compared to our previous group of young adults. No significant effects of cerebellar tDCS were observed. Conclusions Our findings are in line with other studies that have failed to prove robust effects of cerebellar tDCS on motor learning. The present findings, however, do not exclude cerebellar tDCS effects. tDCS effects may be more prominent after repeated stimulation, using other stimulus parameters, in patient populations, or in other motor learning tasks. Trial registration Not applicable.

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“…Moreover, recent follow-up studies have raised questions on the reliability of cerebellar tDCS protocols to enhance motor learning 37,38 . Discussed reasons for the limited robustness of monofocal cerebellar tDCS protocols are the high susceptibility towards variations in task parameters 37 , the large inter-individual differences in the lobule-specific distribution of the applied electric field 39 , and the individual brain-derived neurotrophic factor genotype 40 . One future approach to potentially overcome this current limitation of monofocal cerebellar tDCS might be protocol personalization based on computational modelling approaches, such as electric field dosimetry 41 .…”

Section: Discussionmentioning

confidence: 99%

Multifocal stimulation of the cerebro-cerebellar loop during the acquisition of a novel motor skill

Wessel

Park

Beanato

et al. 2021

Sci Rep

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Transcranial direct current stimulation (tDCS)-based interventions for augmenting motor learning are gaining interest in systems neuroscience and clinical research. Current approaches focus largely on monofocal motorcortical stimulation. Innovative stimulation protocols, accounting for motor learning related brain network interactions also, may further enhance effect sizes. Here, we tested different stimulation approaches targeting the cerebro-cerebellar loop. Forty young, healthy participants trained a fine motor skill with concurrent tDCS in four sessions over two days, testing the following conditions: (1) monofocal motorcortical, (2) sham, (3) monofocal cerebellar, or (4) sequential multifocal motorcortico-cerebellar stimulation in a double-blind, parallel design. Skill retention was assessed after circa 10 and 20 days. Furthermore, potential underlying mechanisms were studied, applying paired-pulse transcranial magnetic stimulation and multimodal magnetic resonance imaging-based techniques. Multisession motorcortical stimulation facilitated skill acquisition, when compared with sham. The data failed to reveal beneficial effects of monofocal cerebellar or additive effects of sequential multifocal motorcortico-cerebellar stimulation. Multimodal multiple linear regression modelling identified baseline task performance and structural integrity of the bilateral superior cerebellar peduncle as the most influential predictors for training success. Multisession application of motorcortical tDCS in several daily sessions may further boost motor training efficiency. This has potential implications for future rehabilitation trials.

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Cerebellar transcranial direct current stimulation interacts with BDNF Val66Met in motor learning

Cited by 15 publications

References 86 publications

Transcranial direct current stimulation of cerebellum alters spiking precision in cerebellar cortex: A modeling study of cellular responses

Transcranial direct current stimulation of cerebellum alters spiking precision in cerebellar cortex: A modeling study of cellular responses

Lack of cerebellar tDCS effects on learning of a complex whole body dynamic balance task in middle-aged (50–65 years) adults

Multifocal stimulation of the cerebro-cerebellar loop during the acquisition of a novel motor skill

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