Cerebellar degeneration affects cortico-cortical connectivity in motor learning networks

Abstract

The cerebellum plays an important role in motor learning as part of a cortico-striato-cerebellar network. Patients with cerebellar degeneration typically show impairments in different aspects of motor learning, including implicit motor sequence learning. How cerebellar dysfunction affects interactions in this cortico-striato-cerebellar network is poorly understood. The present study investigated the effect of cerebellar degeneration on activity in causal interactions between cortical and subcortical regions involved in motor learning. We found that cerebellar patients showed learning-related increase in activity in two regions known to be involved in learning and memory, namely parahippocampal cortex and cerebellar Crus I. The cerebellar activity increase was observed in non-learners of the patient group whereas learners showed an activity decrease. Dynamic causal modeling analysis revealed that modulation of M1 to cerebellum and putamen to cerebellum connections were significantly more negative for sequence compared to random blocks in controls, replicating our previous results, and did not differ in patients. In addition, a separate analysis revealed a similar effect in connections from SMA and PMC to M1 bilaterally. Again, neural network changes were associated with learning performance in patients. Specifically, learners showed a negative modulation from right SMA to right M1 that was similar to controls, whereas this effect was close to zero in non-learners. These results highlight the role of cerebellum in motor learning and demonstrate the functional role cerebellum plays as part of the cortico-striato-cerebellar network.

Motor sequence learning deficits in idiopathic Parkinson’s disease are associated with increased substantia nigra activity

“…Thus, these results indicate that despite a lack of improvement in RT, some implicit sequence-specific learning was evident in all subjects. Note that using this exact same task, we have previously shown that younger healthy controls were faster during SEQ compared to RND blocks, while persons with cerebellar degeneration were not (Tzvi et al, 2017). Together with the current results, this suggests that age and neurological deficits impact on the ability to improve RT in this task.…”

“…We also allowed an intrinsic connection between homolog M1 based on previous work (Tzvi et al, 2017). In addition, our previous fMRI studies of MSL showed that specifying the right cerebellum as input node leads to highest exceedance probability (Tzvi et al, 2017(Tzvi et al, , 2015(Tzvi et al, , 2014. We therefore chose this node as input here as well.…”

“…Theoretical models suggest that motor learning is implemented through specific cortico-striatal and cortico-cerebellar circuits, which mediate different learning stages (Doyon et al, 2009). Previously, we tested this model in healthy subjects and found that learning negatively modulated connections from M1 to cerebellum (Tzvi et al 2014) but also between putamen and cerebellum (Tzvi et al 2015;Tzvi et al 2017). This suggests that besides the cerebellum, the putamen may also play an important role in acquisition of new motor sequences.…”

General Management of Cerebellar Disorders: An Overview

“…For example, alterations in networks including the cerebellum have been identified, which correlate to the degrees of motor adaptation in visuomotor adaptation tasks in healthy subjects (Albert et al 2009;Della-Maggiore et al 2009). More recently, Tzvi et al (2017) found that changes in fMRI signal and functional connectivity in the cortico-striatocerebellar motor learning network were associated with learning performance in patients with cerebellar degeneration in a sequence learning task.…”

New Horizons in Early Dementia Diagnosis: Can Cerebellar Stimulation Untangle the Knot?

“…The cerebellum has been growingly emphasized among the potential target of non-invasive neurostimulation to induce changes in cortico-cortical connectivity [32,33,34,35,36,37,38,39,40,41,42,43,44,45,46]. This is not surprising, if we take into account the growing evidence on complex and multiple connections of the cerebellum with the cerebrum to modulate cortical connectivity within the networks that are critical to orchestrate cognitive, emotional, and sensorimotor processes (including the default mode network and frontoparietal networks) [20,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47].…”