Distinct Contribution of the Cortico-Striatal and Cortico-Cerebellar Systems to Motor Skill Learning Julien Doyon A,C,∗, Virginia Penhune B, Leslie G

Neuropsychologia 41 (2003) 252–262 Distinct contribution of the cortico-striatal and cortico-cerebellar systems to motor skill learning Julien Doyon a,c,∗, Virginia Penhune b, Leslie G. Ungerleider c a Department of Psychology, University of Montreal, P.O. Box 6128, Downtown Station, Montreal, Que., Canada H3C3J7 b Department of Psychology, Concordia University, 7141 Sherbrooke West, Montreal, Que., Canada H4BIR6 c Laboratory of Brain and Cognition, NIMH, NIH, Bethesda, MD, USA Abstract This review paper focuses on studies in healthy human subjects that examined the functional neuroanatomy and cerebral plasticity associated with the learning, consolidation and retention phases of motor skilled behaviors using modern brain imaging techniques. Evidence in support of a recent model proposed by Doyon and Ungerleider [Functional Anatomy of Motor Skill Learning. In: Squire LR, Schacter DL, editors. Neuropsychology of Memory. New York: Guilford Press, 2002.] is also discussed. The latter suggests that experience-dependent changes in the brain depend not only on the stage of learning, but also on whether subjects are required to learn a new sequence of movements (motor sequence learning) or learn to adapt to environmental perturbations (motor adaptation). This model proposes that the cortico-striatal and cortico-cerebellar systems contribute differentially to motor sequence learning and motor adaptation, respectively, and that this is most apparent during the slow learning phase (i.e. automatization) when subjects achieve asymptotic performance, as well as during reactivation of the new skilled behavior in the retention phase. © 2002 Elsevier Science Ltd. All rights reserved. Keywords: Cortico-striatal systems; Cortico-cerebellar systems; Motor skill learning; Motor required learning; Motor adaptation; PET; EURI 1. Introduction in a sequence, come to be performed effortlessly through repeated practice [68]. In everyday life, we go about activities using a variety of In both animals and humans, motor skill learning is usu- motor skills that have been acquired gradually through prac- ally measured by a reduction in reaction time and the num- tice and interactions with our environment. These include, ber of errors, and/or by a change in movement synergy and for example, the use of smooth co-articulation of finger kinematics (e.g. [5–7,24,30,57,60] for reviews). For some movements into a specific sequence (e.g. when playing a skills, such as learning to play a new melody on a musical musical instrument like the piano), of regular multi-joint instrument, early learning can be facilitated using explicit movement synergies (e.g. during reaching and grasping of knowledge (i.e. requiring thought). For most motor skills, small objects), and of a smoothly executed eye-body coor- however, motor performance is ultimately over-learned to a dinated action (e.g. in playing sports such as golf). To study point where it can be performed implicitly (i.e. without con- the time course, the biomechanics, the learning mechanisms scious recollection). As opposed to other forms of memory (e.g. implicit versus explicit) and the neural substrates me- (e.g. episodic memory), these changes in performance are diating our ability to learn such skilled behaviors in the known to evolve slowly, requiring many repetitions over sev- laboratory, investigators have used experimental paradigms eral training sessions [30,60]. Indeed, psychophysical stud- that fall into two categories: the first measures the incremen- ies have demonstrated that the incremental acquisition of tal acquisition of movements into a well-executed behavior motor skills follows two distinct stages: first, an early, fast (motor sequence learning), whereas the second tests our learning stage in which considerable improvement in per- capacity to compensate for environmental changes (motor formance can be seen within a single training session; and adaptation) (e.g. [8,11,15,18,31,32,57,58]). Operationally second, a later, slow stage in which further gains can be defined, these two forms of motor skill learning refer to observed across several sessions (and even weeks) of prac- the process by which movements, either produced alone or tice [4,32,42]. In addition to these two stages, an interme- diate phase corresponding to a consolidation period of the ∗ Corresponding author. Tel.: +1-514-343-6502; fax: +1-514-343-5787. motor routine has recently been proposed, as gains in per- E-mail address: [email protected] (J. Doyon). formance have been reported following a latent period of 0028-3932/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S0028-3932(02)00158-6 J. Doyon et al. / Neuropsychologia 41 (2003) 252–262 253 more than 6 h after the first training session without addi- [21,42,61]), as well as from lesion experiments in rodents tional practice on the task (e.g. [26,33]). Additionally, there (e.g. [36,67] for a review) and non-human primates (e.g. is little or no interference from a competing task, provided [35,38]). More recently, modern brain imaging techniques it is administered beyond a critical time window of about have allowed us to confirm not only the functional contribu- 4–6 h [4,49,57]. Finally, with extended practice, the skilled tion of both cortico-striatal and cortico-cerebellar systems behavior is thought to become resistant both to interference in motor skill learning, but also to identify in vivo the neural and to the simple passage of time [45]. Once over-learned, substrates mediating this type of memory and the functional a motor skill can thus be readily retrieved with reasonable dynamic changes that occur over the entire course of the performance despite long periods without practice. acquisition process (e.g. see [5,9,10,30,64,65] for reviews). Based on animal and human work, several brain struc- In this review paper, we will discuss the results of stud- tures, including the striatum, cerebellum, and motor cor- ies in healthy human subjects that examined the functional tical regions of the frontal lobe have been thought to anatomy and the cerebral plasticity associated with the be critical for the acquisition and/or retention of mo- learning, consolidation and retention phases of motor skilled tor skilled behaviors (e.g. [2,5,9,10,14,19,30,53,62,64,65] behaviors using brain imaging technology, such as positron for reviews). Anatomical studies have demonstrated that emission tomography (PET) and functional magnetic res- these structures form two distinct cortical-subcortical onance imaging (fMRI). Previous literature reviews have circuits: a cortico-basal ganglia-thalamo-cortical loop often pointed out the heterogeneity in the results obtained and a cortico-cerebello-thalamo-cortical loop [37,46,61] with this methodological approach [5,10,15,65]. However, (see Fig. 1). Evidence supporting the role of these Doyon and Ungerleider [10] have recently proposed that cortical-subcortical systems in motor skill learning has come much of the variability in the pattern of results across stud- from impairments found in patients with striatal dysfunction ies can be accounted for if one considers the type of motor (e.g. in Parkinson’s or Huntington’s disease), with damage task and the learning phase at which subjects are scanned. to the cerebellum, or with a circumscribed lesion involving The latter model suggests that the cortico-striatal and the frontal motor areas (e.g. [1,6,7,13,22,44,52,69]). Fur- cortico-cerebellar systems contribute differentially to motor ther support has come from neurophysiological studies (e.g. sequence learning and motor adaptation, respectively, and that this is most apparent during the slow learning phase (i.e. automatization) when subjects achieve asymptotic performance, as well as during reactivation of the new skilled behavior in the retention phase. In support of this model, we will put emphasis on the results of our own series of experiments with tasks designed to investigate the neural substrate mediating motor sequence learning, and will also describe in more detail some of the studies that focused on the neuronal system involved in motor adaptation. 2. Neural correlates of motor sequence learning In brain imaging investigations designed to better under- stand the neuroanatomy of motor skill learning, subjects are typically required to produce a sequence of movements that they know explicitly before scanning [9,31,32,54,56], to dis- cover a particular sequence by trial and error [27–29,50,63], or to follow the display of visual stimuli appearing sequen- tially on a screen [6,9,15,23,47,48]. The motor responses in those tasks involve finger-to-thumb opposition movements (e.g. [31,32,56]), finger presses on response boxes (e.g. [15,47,48]) or movements of the whole arm (e.g. [8,16]). Fig. 1. Diagram illustrating the major cortical and subcortical structures in- However, other sequence tasks, including rotor pursuit volved in motor skill learning, and their interconnections. These structures [17,18], the tracing of cut-out mazes [66], and the practice are organized into two main circuits: a cortico-striato-thalamo-cortical loop of repeating two-dimensional trajectorial movements [55] and a cortico-cerebello-thalamo-cortical loop. Dynamic changes within have also been employed in previous brain imaging studies these loops occur during motor sequence learning and motor adaptation to examine this form of motor learning. (see text for more details): SMA, supplementary motor area; PM, pre- motor cortex; M1, primary motor cortex;

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