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Acknowledgements:We would like to thank Susanne Schellbach and Christian Erdmann for assisting with data acquisition, Steffan Frässle for helpful advice on dynamic causal modelling, and Matthias Liebrand for helpful discussions on this work. This study was supported by internal funding of the University of Lübeck. UMK and TFM are supported by the DFG.peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/136820 doi: bioRxiv preprint first posted online May. 11, 2017; AbstractThe 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 modelling 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.peer-reviewed)

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 α oscillations for communication within the 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 α power and cross-channel coherence shortly before the motor response. We found a gradual decrease in learning-related α power over left premotor cortex (PMC) and somatosensory areas. Connectivity between left PMC and right cerebellum was reduced for sequence learning, possibly reflecting a functional decoupling in the premotor-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 α power following rCB tACS was increased in PMC, possibly reflecting a decrease of neural activity. Importantly, learning-specific coherence between left PMC and a right cerebellar cluster was enhanced following rCB tACS. These findings suggest that interactions within a premotor-cerebellar loop, which are underlying motor sequence learning, are mediated by α oscillations. We show that they can be modulated through external entrainment of cerebellar oscillations, which modulates motor cortical α and interferes with sequence learning.

1Damage to the orbitofrontal cortex (OFC) can cause maladaptive social behavior, but the cognitive 2 processes underlying these behavioral changes are still uncertain. Here, we tested whether patients with 3 acquired OFC lesions show altered approach-avoidance tendencies to emotional facial expressions. 4Thirteen patients with focal OFC lesions and 31 age-and gender-matched healthy controls performed an 5 implicit approach-avoidance task in which they either pushed or pulled a joystick depending on stimulus 6 color. While controls avoided angry faces, OFC patients displayed an incongruent response pattern 7 characterized by both increased approach and reduced avoidance of angry facial expressions. The 8 approach bias was stronger in patients with higher self-reported impulsivity and disinhibition, and in those 9 with larger lesions. Moreover, patients committed more errors in the task, which in turn was correlated with 10 self-rated clinical impairment. We further used linear ballistic accumulator modelling to investigate latent 11 parameters underlying approach-avoidance decisions. Controls displayed negative drift rates when 12 approaching angry faces, whereas OFC lesions abolished this bias. In addition, OFC patients had weaker 13 response drifts than controls during angry face avoidance. Finally, patients showed generally reduced 14 variability in drift rates and shorter non-decision times, indicating impulsive and rigid decision-making. In 15 sum, our findings suggest that OFC damage alters the pace of evidence accumulation in response to threat 16 signals, eliminating a default, protective avoidant bias and facilitating dysfunctional approach behavior. 17 18

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