Review
Brain stimulation studies of non-motor cerebellar function: A systematic review

https://doi.org/10.1016/j.neubiorev.2013.03.001Get rights and content

Highlights

  • We review all cerebellar non-motor non-invasive stimulation studies.

  • Effects seen in learning, memory, cognition, emotions, perception and timing.

  • Diversity seen in stimulation parameters and targets despite similar tasks.

  • Neuronavigation approaches shown to be beneficial.

  • Improved understanding of physiology of stimulation essential.

Abstract

Evidence for a cerebellar role in non-motor functions has been demonstrated by clinical and neuroimaging research. These approaches do not allow causal relationships to be inferred though the experimental manipulation of the cerebellum. Transcranial magnetic and current stimulation may allow better understanding of the cerebellum via the temporary alteration of its operation in healthy volunteers. This review examined all studies of the cerebellar role in non-motor functions using non-invasive brain stimulation. Of 7585 papers captured by an initial search, 26 met specific selection criteria. Analysis revealed behavioural effects across learning, memory, cognition, emotional processing, perception and timing, though the results were not sufficiently similar as to offer a definitive statement of the cerebellum's role. The non-invasive application of stimulation to the cerebellum presents challenges due to surrounding anatomy and the relatively small target areas involved. This review analysed the methods used to address these challenges with a view to suggesting methodological improvements for the establishment of standards for the location of cerebellar stimulation targets and appropriate levels of stimulation.

Introduction

The cerebellum has traditionally been viewed as a brain structure involved in the implementation of motor behaviour. Early clinical studies e.g. (Luciani, 1891) suggested that damage to the cerebellum resulted in a loss of muscle tone, disorganisation of movement and loss of balance. Several early investigators also noted cognitive and psychiatric changes in patients who had suffered cerebellar injury (reviewed in Schmahmann, 2010). These suggestions of non-motor cerebellar function were largely ignored in subsequent investigations as the reported effects were often subtle, contradictory and overshadowed by the effects of cerebral damage. Consideration of cerebellar contributions to non-motor behaviour was not part of mainstream research for several decades. In recent years, however, there has been renewed interest in the possibility of the cerebellum playing a role in autonomic, affective and cognitive functions with findings derived from newly available technologies. It is the purpose of this systematic review to examine the use of several recently developed brain stimulation techniques in the investigation of cerebellar contributions to non-motor behaviour. This review will examine the methodology and findings of studies that have used transcranial current stimulation and transcranial magnetic stimulation of the cerebellum and discuss the contribution that brain stimulation techniques may make to cerebellar research.

Cerebellar stimulation has been used in recent years in an attempt to corroborate evidence gained from imaging and clinical work as to cerebellar involvement in non-motor behaviour, to infer the nature of this role and to localise function within the cerebellum. A wide range of tasks, targets and techniques has been used in this research and it is therefore appropriate to review the approaches taken in order to determine which approaches have proved most successful, to summarise the information that has been gained and to highlight the difficulties encountered so that methodological improvements may be suggested.

A further motivation for this review is that the nature of any cerebellar contribution to non-motor behaviours remains somewhat controversial and therefore examination of the findings of relevant studies may be of use within this context.

This review will first discuss the parameters used and the methodological decisions taken across all studies and then examine groups of studies categorised according to the behavioural function targeted.

Section snippets

Methods

A PubMed search was performed using the following search terms without restriction of date or database field: ((cerebellum) OR (cerebellar)) AND ((stimulation) OR (transcranial) OR (theta burst)). This search returned 7585 papers, which were assessed according to the following inclusion criteria:

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    Living, neurologically normal, human subjects

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    Cerebellar stimulation target

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    Magnetic or electrical stimulation

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    Transcranial, rather than deep brain or cortical stimulation

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    Non-motor

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    Not purely physiological,

Discussion

The results of our review showed that several transcranial magnetic stimulation (TMS) paradigms have been employed for cerebellar non-motor research. The paradigms used can be divided into single pulse and repetitive TMS (see Walsh and Rushworth, 1999 for a discussion of their differences). Single pulse TMS is generally delivered at an intensity sufficient to generate action potentials in targeted brain regions: this externally triggered discharge of neurons introduces temporary disorder into

Conclusion

Emerging from this review is a clear picture of the challenges involved in cerebellar stimulation, both in terms of methods and the interpretation of results. The diversity of targets selected for the stimulation of similar cerebellar regions highlights the benefits of using neuronavigation where available. Skull landmarks can be unreliable indicators of the presence of larger, cerebral regions, such as the dorsolateral prefrontal cortex (e.g. Herwig et al., 2001); these issues may be even more

Acknowledgement

We acknowledge the financial support of the Future and Emerging Technologies (FET) programme within the Seventh Framework Programme for Research of the European Commission, under FET-Open grant number: 222079 (HIVE) to RMB.

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