Biology subjects

Classen, J.

Publications and source records attributed to Classen, J..

3 recordsLinked to original sources

bioRxiv2020

Motor sequence learning deficits in idiopathic Parkinsons disease are associated with increased substantia nigra activity

Previous studies have shown that persons with Parkinsons disease (pwPD) share specific deficits in learning new sequential movements, but the neural substrates of this impairment remain unclear. In addition, the degree to which striatal dopaminergic denervation in PD affects the cortico-striato-cerebellar motor learning network remains unknown. We aimed to answer these questions using fMRI in 16 pwPD and 16 healthy age-matched control subjects while they performed an implicit motor sequence learning task. While learning was absent in both pwPD and controls assessed with reaction time differences between sequential and random trials, larger error-rates during the latter suggest that at least some of the complex sequence was encoded. Moreover, we found that while healthy controls could improve general task performance indexed by decreased reaction times across both sequence and random blocks, pwPD could not, suggesting disease-specific deficits in learning of stimulus-response associations. Using fMRI, we found that this effect in pwPD was correlated with decreased activity in the hippocampus over time. Importantly, activity in the substantia nigra (SN) and adjacent bilateral midbrain was specifically increased during sequence learning in pwPD compared to healthy controls, and significantly correlated with sequence-specific learning deficits. As increased SN activity was also associated (on trend) with higher doses of dopaminergic medication as well as disease duration, the results suggest that learning deficits in PD are associated with disease progression, indexing an increased drive to recruit dopaminergic neurons in the SN, however unsuccessfully. Finally, we found no differences between pwPD and controls in task modulation of the cortico-striato-cerebellar network. Notably, in both groups Bayesian model selection revealed cortico-cerebellar connections modulated by the task, suggesting that despite behavioral and activation differences, the same cortico-cerebellar circuitry is recruited for implementing the motor task.

neuroscience↗

bioRxiv2020

Beneficial effects of cerebellar tDCS on motor learning are associated with altered putamen-cerebellar connectivity: a simultaneous tDCS-fMRI study

Non-invasive transcranial stimulation of cerebellum and primary motor cortex (M1) has been shown to enhance motor learning. However, the mechanisms by which stimulation improves learning remain largely unknown. Here, we sought to shed light on the neural correlates of transcranial direct current stimulation (tDCS) during motor learning by simultaneously recording functional magnetic resonance imaging (fMRI). We found that right cerebellar tDCS, but not left M1 tDCS, led to enhanced sequence learning in the serial reaction time task. Performance was also improved following cerebellar tDCS compared to sham in a sequence production task, reflecting superior training effects persisting into the post-training period. These behavioral effects were accompanied by increased learning-specific activity in right M1, left cerebellum lobule VI, left inferior frontal gyrus and right inferior parietal lobule during cerebellar tDCS compared to sham. Despite the lack of group-level changes comparing left M1 tDCS to sham, activity increase in right M1, supplementary motor area, and bilateral superior frontal cortex, under M1 tDCS, was associated with better sequence performance. This suggests that lack of group effects in M1 tDCS relate to inter-individual variability in learning-related activation patterns. We further investigated how tDCS modulates effective connectivity in the cortico-striato-cerebellar learning network. Using dynamic causal modelling, we found altered connectivity patterns during both M1 and cerebellar tDCS when compared to sham. Specifically, during cerebellar tDCS, negative modulation of a connection from putamen to cerebellum was decreased for sequence learning only, effectively leading to decreased inhibition of the cerebellum. These results show specific effects of cerebellar tDCS on functional activity and connectivity in the motor learning network and may facilitate the optimization of motor rehabilitation involving cerebellar non-invasive stimulation.

neuroscience↗

bioRxiv2020

The role of alpha oscillations in a premotor-cerebellar loop in modulation of motor learning: insights from transcranial alternating current stimulation

Alpha oscillations (8-13 Hz) have been shown to play an important role in dynamic neural processes underlying learning and memory. The goal of this study was to scrutinize the role of oscillations in communication within a network implicated in motor sequence learning. To this end, we conducted two experiments using the serial reaction time task. In the first experiment, we explored changes in power and cross-channel coherence. We found a gradual decrease in learning-related power over left premotor cortex (PMC), somatosensory cortex (S1) and tempo-parietal junction (TPJ). Alpha coherence between left PMC/S1 and right cerebellar crus I was reduced for sequence learning, possibly reflecting a functional decoupling in a motor-cerebellar loop during the motor learning process. In the second experiment in a different cohort, we applied 10Hz transcranial alternating current stimulation (tACS), a method shown to entrain local oscillatory activity, to left M1 (lM1) and right cerebellum (rCB) during sequence learning. We observed learning deficits during rCB tACS compared to sham, but not during lM1 tACS. In addition, learning-related power following rCB tACS was increased in left PMC, possibly reflecting a decrease in neural activity. Importantly, learning-specific coherence between left PMC and right cerebellar lobule VIIb was enhanced following rCB tACS. These findings suggest that interactions within a premotor-cerebellar loop, which are underlying motor sequence learning, are mediated by oscillations. We show that they can be modulated through external entrainment of cerebellar oscillations, which then modulates motor cortical and interferes with sequence learning.

neuroscience↗