Brain Stimulation | 2021
Non-invasive stimulation of the motor cerebellum has potential cognitive confounds
Abstract
The cerebellum has been known to play an important role in motor control for over a century. Seminal work by Holmes highlighted that damage to the cerebellum severely impairs motor coordination [1]. Converging evidence from behavioural, neurophysiological, neuropsychological, and neuroimaging studies has since highlighted the functional role of cerebellar-motor interactions in motor behaviours. Specifically, cerebellar lobules IV-VI and VIIB-VIII (which we will refer to as the “motor cerebellum”) have reciprocal anatomical connections with cortical motor areas [2]. Somatotopically organised primary and secondarymotor representations that functionally interact with the primary motor cortex have been described in cerebellar lobules V and VIII respectively [3]. These cerebellar-motor networks have been established as playing a critical role in motor control. The cerebellum also plays a well-documented role in higherorder functions [2,4,5]. In primates, cerebellar Crus I and Crus II are reciprocally connected to prefrontal cognitive areas [2,3,5,6]. Clinically, cerebellar lesions or atrophy can lead to “Cerebellar Cognitive Affective Syndrome”, which is characterized by problems in executive function, affect, and language [4]. Functional neuroimaging and non-invasive brain stimulation studies in healthy populations similarly demonstrate a cerebellar role in cognition and language [7,8] with Crus I and II specifically involved in these higher-order functions [6]. This has led to a general consensus that prefrontal-projecting Crus I and II (which wewill operationally define as the “cognitive cerebellum”) contribute to higher-order functions such as cognition and language [5]. Critically, the division of motor and cognitive function within the cerebellum is often overlooked in studies using transcranial stimulation. A large body of work has aimed to modulate cerebellar function through non-invasive brain stimulation [9], and themajority of this research aims to affect motor function. However, it is difficult to stimulate motor regions of the cerebellum without also stimulating the overlying cognitive cerebellum (Fig. 1; see also [10]). Cerebellar Transcranial Magnetic Stimulation (TMS) and transcranial Direct Current stimulation (tDCS) targeting motor functions typically place the coil or stimulating electrode 3cm lateral to the inion, or 3cm lateral and 1cm inferior to the inion. However, from these positions, any stimulation reaching the deep lying motor cerebellumwould first have to pass through the cognitive cerebellum. We therefore argue that it is important to carefully consider potential cognitive confounds in cerebellar stimulation studies aiming to affect motor circuitry. Findings from non-invasive stimulation studies are consistent with our proposal that successfully affecting the function of the pathway between the cerebellum and primary motor cortex