Over the past years, the concept of non-motor cerebellar functions has gathered growing attention becoming a reliable focal point for neuroscience investigators.

The cerebellum receives and sends information from various brain regions, cerebellar function is strongly associated with the hippocampus, and the cerebellum influences hippocampal activity, including spatial navigation (Rochefort et al., 2011; Rondi-Reig et al., 2014; Lefort et al., 2015). Information about the influence of the cerebellum on the navigation system comes from studies using electrophysiological, anatomical, and behavioral analyses in both human and animal models (Rochefort et al., 2013).

Ample information on the cerebellum’s spatial function comes from experiments conducted on rats, mice and goldfish (Petrosini et al., 1996; Durán et al., 2014). Studies involving different cerebellar mutant mice strains or using hemi-cerebellectomy combined with widely ranging protocols have reported selective deficits in these animals’ spatial functions. Some studies have proposed that this impairment is related more to the procedural navigational component (inability to organize and execute complex and effective exploration behaviors) than to the declarative component (an inability to develop an internal environment map).

Earlier findings suggesting that the cerebellum influences path integration, a function that incorporates proprioceptive and vestibular information as a subject moves through the environment (McNaughton et al., 2006). Rather than encoding a spatial map of the environment the cerebellum computes self-motion information from the various sources required to build the body’s representation in space (Rochefort et al., 2013). The cerebellum contributes to spatial navigation at two levels, first in processing the self-motion information required to build spatial representation, and second in using this spatial representation to perform an optimal trajectory toward a goal. The cerebellar network participates in map formation in the forebrain navigation areas by specifically encoding and computing self-motion information(Rochefort et al., 2013).

Over recent years, evidence involving the cerebellar region in non-motor functions has made it of interest as a target for electrical neuromodulation, intended to alter the acquisition of spatial knowledge and skills (Brunyé et al., 2014; Oldrati et al., 2018).

One of the most often used virtual reality tasks for investigating spatial navigation tasks comprises two phases: encoding, in which participants actively navigate the environment and learn the spatial locations for one object, and retrieval, in which they retrieve the position of the object they have discovered and memorized in the previous encoding phase, starting from another starting point. Specifically, this “re-orientation task” forces participants to refer to the long-term stored allocentric environmental representation and synchronize it with new upcoming egocentric inputs to solve the task, thus making it an effective procedure for assessing egocentric-to-allocentric translation ability (Bosco et al., 2008; Serino and Riva, 2015).

To our knowledge, few researches have addressed transcranial direct current stimulation (tDCS) and spatial navigation in a virtual environment (Brunyé, 2018; Brunyé et al., 2018) and no published studies have studied the effect of cerebellar tDCS. Having his information would help us to understand more about the possible role of the cerebellum in spatial navigation thereby advancing research to develop better cognitive treatment outcome measures (Coughlan et al., 2018) also for use in patients with neurological syndromes who have deficits in spatial navigation and orientation.

In this pilot study, we used a virtual navigation task in healthy subjects to investigate whether cerebellar tDCS influences spatial navigation.

No differences were found between the two groups for age (t₃₈ = 1.31; p = 0.2), education (t₃₈ = -0.41; p = 0.2), and gender ( = 0.52; p = 0.75) (Table 1). Independent sample t-tests underlined that accuracy indexes remained unchanged regardless of the type of stimulation (Offset: t₃₈ = -1.32; p = 0.2; d = 0.366; DistanceRet: t₃₈ = 1.22; p = 0.23; d = 0.126; TimeRet: t₃₈ = 1.2; p = 0.24; d = 0.118) effect sizes of Cohen’s d equal to 0.2, are considered small, 0.5 considered medium, and 0.8 considered large) (Cohen, 1988). The univariate ANCOVAs showed that the individual visuospatial learning abilities had no effect on the navigation performances (Offset: F(1.37) = 0.05; p = 0.83; η² = 0.001; DistanceRet: F(1.37) = 0.04; p = 0.85; η² = 0.001; TimeRet: F(1.37) = 0.36; p = 0.55; η² = 0.01). Similarly, stimulation induced no changes in attention abilities (RTs: Time X Stimulation F(1.38) = 0.06; p = 0.81; η² = 0.002).

The second statistical approach based on Bayesian analyses confirmed that cerebellar tDCS left the accuracy indexes unchanged. The estimated Bayes factors (null/alternative) indicated that the data would fit better under the null hypothesis than under the alternative one, 1.8 times for the DistanceRet, 1.62 times for Offset and 1.84 times for TimeRet (Table 1). In accordance with recommendations by Wetzels et al. (2011), the obtained Bayes Factor indicated anecdotal evidence (Table 1).

Our findings in this pilot study show that in healthy subjects, cerebellar tDCS leaves the retrieval phase in the virtual navigation task – a measure that reflects the spatial navigation system – unchanged.

The first researchers to identify the crucial role of the cerebellum in the motor and cognitive aspects of navigation were Igloi et al. (2015) using a virtual reality task, highlighting a functional interaction between the cerebellum and the hippocampus to support spatial encoding. As recently reviewed by Rochefort et al. (2013), the cerebellum may specifically contribute to two major brain circuits supporting the representation of space in the hippocampal system: one involving the retrosplenial cortex, responsible for the egocentric-allocentric transformation (Vann et al., 2009); and the other involving the posterior parietal cortex, responsible for egocentric representations (Taube, 2007).

Of importance when interpreting our results, we emphasize that our individual participants’ navigation experiences differed markedly in quantity and quality. Although during navigation tasks, subjects probably use two different strategies, one egocentric and the other allocentric (Serino and Riva, 2015), we did not explore the relationships between these abilities with quantitative measures. We conjecture that in our study, during the retrieval phase, subjects used allocentric strategies more extensively than egocentric strategies whereas in the “encoding” phase during the virtual navigation task, they used an egocentric learning spatial strategy based on praxis strategies, related to procedural learning (Schenk and Morris, 1985).

Because the cerebellum is primarily involved in acquiring procedural aspects of the spatial tasks whereas the hippocampus is more involved in recollecting previous episodic spatial experiences (Petrosini et al., 1996; Burgess et al., 2002; Valenzuela et al., 2003), whether stimulation delivered before the encoding phase might be more effective than stimulation delivered before the retrieval phase remains to be tested in a specifically designed experiment.

Why cerebellar tDCS failed to influence navigation more effectively could also depend on several factors including the type of stimulation delivered (anodal-cathodal). Because cerebellar tDCS studies have assessed neurophysiological, cognitive, affective, as well as behavioral variables with heterogeneous methodologies, interpreting the effects induced by anodal or cathodal stimulation is a far more complex task for cerebellar tDCS than for cerebral tDCS. Equally important, the stimulation site (unilateral or bilateral cerebellum), reference electrode position and stimulation variables (intensity, duration, electrode size) differed across the various studies (Ferrucci and Priori, 2014; Ferrucci et al., 2015; van Dun et al., 2017; Oldrati and Schutter, 2018). Several methodological variables for cerebellar tDCS therefore need to be systematically assessed. Cerebellar tDCS remains poorly understood and in general, no clear reference standards exist for tDCS dose and montage.

This study has some limitations. First is the small sample size, though large enough for a pilot study, and the inter-individual variability. Another limitation is that we delivered cerebellar tDCS only before the retrieval phase.

Further studies enrolling a larger sample and testing a different stimulation protocol in another virtual reality task phase may be useful in understanding better the cerebellum’s specific role in spatial navigation.

RF conceived and performed the experiments, analyzed the data, and wrote the paper. SS, FR, and CR conducted the experiments, analyzed the data, and wrote the paper. DC and EP conducted the experiments. SM analyzed the data and wrote the paper. GR and AP conceived the experiments, coordinated the research, and reviewed the paper. All authors critically revised and approved the final manuscript.

RF, SM, and AP are founders and stakeholders of Newronika srl, which is a spin-off company of the University of Milan and of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico. AP is on the scientific advisory board of the same Newronika srl spin-off company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.