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Background Learning and learning-related neuroplasticity in motor cortex are potential mechanisms mediating recovery of movement abilities after stroke. These mechanisms depend on dopaminergic projections from midbrain that may encode reward information. Likewise, therapist experience confirms the role of feedback/reward for training efficacy after stroke. Objective To test the hypothesis that rehabilitative training can be enhanced by adding performance feedback and monetary rewards. Methods This multicentric, assessor-blinded, randomized controlled trial used the ArmeoSenso virtual reality rehabilitation system to train 37 first-ever subacute stroke patients in arm-reaching to moving targets. The rewarded group (n = 19) trained with performance feedback (gameplay) and contingent monetary reward. The control group (n = 18) used the same system without monetary reward and with graphically minimized performance feedback. Primary outcome was the change in the two-dimensional reaching space until the end of the intervention period. Secondary clinical assessments were performed at baseline, after 3 weeks of training (15 1-hour sessions), and at 3 month follow-up. Duration and intensity of the interventions as well as concomitant therapy were comparable between groups. Results The two-dimensional reaching space showed an overall improvement but no difference between groups. The rewarded group, however, showed significantly greater improvements from baseline in secondary outcomes assessing arm activity (Box and Block Test at post-training: 6.03±2.95, P = .046 and 3 months: 9.66±3.11, P = .003; Wolf Motor Function Test [Score] at 3 months: .63±.22, P = .007) and arm impairment (Fugl-Meyer Upper Extremity at 3 months: 8.22±3.11, P = .011). Conclusions Although neutral in its primary outcome, the trial signals a potential facilitating effect of reward on training-mediated improvement of arm paresis. Trial registration ClinicalTrials.gov (ID: NCT02257125).

BACKGROUND Imaging studies point to a posture (finger vs. hand) and domain-specific neural basis of gestures. Furthermore, modulation of gestures by theta burst stimulation (TBS) may depend on interhemispheric disinhibition. OBJECTIVE/HYPOTHESIS In this randomized sham-controlled study, we hypothesized that dual site continuous TBS over left inferior frontal gyrus (IFG-L) and right inferior parietal gyrus (IPL-R) predominantly affects pantomime of finger postures. Furthermore, we predicted that dual cTBS improves imitation of hand gestures if the effect correlates with measures of callosal connectivity. METHODS Forty-six healthy subjects participated in this study and were targeted with one train of TBS in different experimental sessions: baseline, sham, single site IFG-L, dual IFG-L/IPL-R, single site IPL-R. Gestures were evaluated by blinded raters using the Test for Upper Limb Apraxia (TULIA) and Postural Imitation Test (PIT). Callosal connectivity was analyzed by diffusion tensor imaging (DTI). RESULTS Dual cTBS significantly improved TULIA$_{total}$ (F [3, 28] = 4.118, p = .009), but did not affect TULIA$_{pantomime}$. The beneficial effect was driven by the cTBS over IPL-R, which improved TULIA$_{imitation}$ (p = .038). Furthermore, TULIA$_{imitation}$ significantly correlated with the microstructure (fractional anisotropy) of the splenium (r = 0.420, p = .026), corrected for age and whole brain volume. CONCLUSIONS The study suggests that inhibition of IPL-R largely accounted for improved gesturing, possibly through transcallosal facilitation of IPL-L. Therefore, the findings may be relevant for the treatment of apraxic stroke patients. Gesture pantomime and postural gestures escaped the modulation by dual cTBS, suggesting a more widespread and/or variable neural representation.

INTRODUCTION Motor skill learning can help stroke survivors to cope with motor function deficits but requires many repetitions. One factor that keeps patients motivated is obtaining reward upon successfully completing a motor task. It has been suggested that stroke survivors have deficits in reward processing which may negatively impact skill learning. OBJECTIVE To test the hypothesis that stroke survivors have deficient reward processing during motor skill learning evident in reduced activation in the striatum and its subdivisions in functional magnetic resonance imaging as compared with healthy, age-matched control subjects. METHODS Striatal activity in response to performance dependent feedback and monetary reward was measured in 28 subacute stroke patients and 18 age-matched healthy control subjects during the training of visuomotor tracking an arc-shaped trajectory using the wrist (unimpaired side in patients, dominant side in controls) in an fMRI scanner. RESULTS Despite comparable monetary rewards, stroke patients showed reduced activation in the ventral part (p < 0.01), but not in the dorsal part of the striatum (p = 0.11). 14 patients had their lesion extending into the striatum. The nucleus accumbens as part of the ventral striatum was unlesioned in all participants and still showed a marked hypoactivation in stroke patients as compared with controls (p < 0.001), a finding that could not be explained by motivational differences between the groups. CONCLUSION Striatal hypoactivation in stroke survivors may cause impaired consolidation of motor skills. Stronger rewarding stimuli or drug-mediated enhancement may be needed to normalize reward processing after stroke with positive effects on recovery.

Sparse and clustered-sparse temporal sampling fMRI protocols have been devised to reduce the influence of auditory scanner noise in the context of auditory fMRI studies. Here, we report an improvement of the previously established clustered-sparse acquisition scheme. The standard procedure currently used by many researchers in the field is a scanning protocol that includes relatively long silent pauses between image acquisitions (and therefore, a relatively long repetition time or cluster-onset asynchrony); it is during these pauses that stimuli are presented. This approach makes it unlikely that stimulus-induced BOLD response is obscured by scanner-noise-induced BOLD response. It also allows the BOLD response to drop near baseline; thus, avoiding saturation of BOLD signal and theoretically increasing effect size. A possible drawback of this approach is the limited number of stimulus presentations and image acquisitions that are possible in a given period of time, which could result in an inaccurate estimation of effect size (higher standard error). Since this line of reasoning has not yet been empirically tested, we decided to vary the cluster-onset asynchrony (7.5, 10, 12.5, and 15s) in the context of a clustered-sparse protocol. In this study sixteen healthy participants listened to spoken sentences. We performed whole-brain fMRI group statistics and region of interest analysis with anatomically defined regions of interest (auditory core and association areas). We discovered that the protocol, which included a short cluster-onset asynchrony (7.5s), yielded more advantageous results than the other protocols, which involved longer cluster-onset asynchrony. The short cluster-onset asynchrony protocol exhibited a larger number of activated voxels and larger mean effect sizes with lower standard errors. Our findings suggest that, contrary to prior experience, a short cluster-onset asynchrony is advantageous because more stimuli can be delivered within any given period

The aim of the present study was to assess changes in EEG coherence and phase locking between fronto-parietal areas, including the frontal and parietal motor areas, during early audio- and visuo-motor learning of continuous tracking movements. Subjects learned to turn a steering-wheel according to a given trajectory in order to minimise the discrepancy between a changing foreground stimulus (controllable by the subjects) and a constant background stimulus (uncontrollable) for both the auditory and the visual modality. In the auditory condition, we uncovered a learning-related increase in inter-hemispheric phase locking between inferior parietal regions, suggesting that coupling between areas involved in audiomotor integration is augmented during early learning stages. Intra-hemispheric phase locking between motor and superior parietal areas increased in the left hemisphere as learning progressed, indicative of integrative processes of spatial information and movement execution. Further tests show a significant correlation of intra-hemispheric phase locking between the motor and the parietal area bilaterally and movement performance in the visual condition. These results suggest that the motor-parietal network is operative in the auditory and in the visual condition. This study confirms that a complex fronto-parietal network subserves learning of a new movement that requires sensorimotor transformation and demonstrates the importance of interregional coupling as a neural correlate for successful acquisition and implementation of externally guided behaviour

Summary: In everyday life specific situations need specific reactions. Through repetitive practice, such stimulus-response associations can be learned and performed automatically. The aim of the present EEG study was the illustration of learning dependent modifications in neuronal pathways during short-term practice of visuomotor associations. Participants performed a visuomotor association task including four visual stimuli, which should be associated with four keys, learned by trial and error. We assumed that distinct cognitive processes might be dominant during early learning e.g., visual perception and decision making. Advanced learning, however, might be indicated by increased neuronal activation in integration- and memory-related regions. For assessment of learning progress, visual- and movement-related brain potentials were measured and compared between three learning stages (early, intermediate, and late). The results have revealed significant differences between the learning stages during distinct time intervals. Related to visual stimulus presentation, Low Resolution Electromagnetic Brain Tomography (LORETA) revealed strong neuronal activation in a parieto-prefrontal network in time intervals between 100-400 ms post event and during early learning. In relation to the motor response neuronal activation was significantly increased during intermediate compared to early learning. Prior to the motor response (120-360 ms pre event), neuronal activation was detected in the cingulate motor area and the right dorsal premotor cortex. Subsequent to the motor response (68-430 ms post event) there was an increase in neuronal activation in visuomotor- and memory-related areas including parietal cortex, SMA, premotor, dorsolateral prefrontal, and parahippocampal cortex. The present study has shown specific time elements of a visuomotor-memory-related network, which might support learning progress during visuomotor association learning

The aim of the present study was to assess changes in electroencephalogram (EEG) phase locking between fronto-parietal areas, including the frontal and parietal motor areas, during audiomotor learning of continuous tracking movements. Subjects learned to turn a steering wheel according to a given trajectory in order to minimise the discrepancy between a changing foreground stimulus (controllable by the subjects) and a constant background stimulus. The results of the present study show that increasing practice of continuous tracking movements that are continuously performed in the presence of auditory feedback is not accompanied by decrease in phase locking between areas involved. Moreover, the study confirms that internally produced movements show enhanced coherent activities compared to externally guided movements and therefore suggests that the motor-parietal network is more engaged during internally produced than externally produced movements

It has been shown that frontal cortical areas increase their activity during error perception and error processing. However, it is not yet clear whether perception of motor errors is processed in the same frontal areas as perception of errors in cognitive tasks. It is also unclear whether brain activity level is influenced by the magnitude of error. For this purpose, we conducted a study in which subjects were confronted with motor and non-motor errors, and had them perform a sensorimotor transformation task in which they were likely to commit motor errors of different magnitudes (internal errors). In addition to the internally committed motor errors, non-motor errors (external errors) were added to the feedback in some trials. We found that activity in the anterior insula, inferior frontal gyrus (IFG), cerebellum, precuneus, and posterior medial frontal cortex (pMFC) correlated positively with the magnitude of external errors. The middle frontal gyrus (MFG) and the pMFC cortex correlated positively with the magnitude of the total error fed back to subjects (internal plus external). No significant positive correlation between internal error and brain activity could be detected. These results indicate that motor errors have a differential effect on brain activity compared with non-motor errors

BACKGROUND: There is no doubt that good bimanual performance is very important for skilled handball playing. The control of the non-dominant hand is especially demanding since efficient catching and throwing needs both hands. METHODOLOGY/HYPOTHESES: We investigated training-induced structural neuroplasticity in professional handball players using several structural neuroimaging techniques and analytic approaches and also provide a review of the literature about sport-induced structural neuroplastic alterations. Structural brain adaptations were expected in regions relevant for motor and somatosensory processing such as the grey matter (GM) of the primary/secondary motor (MI/supplementary motor area, SMA) and somatosensory cortex (SI/SII), basal ganglia, thalamus, and cerebellum and in the white matter (WM) of the corticospinal tract (CST) and corpus callosum, stronger in brain regions controlling the non-dominant left hand. RESULTS: Increased GM volume in handball players compared with control subjects were found in the right MI/SI, bilateral SMA/cingulate motor area, and left intraparietal sulcus. Fractional anisotropy (FA) and axial diffusivity were increased within the right CST in handball players compared with control women. Age of handball training commencement correlated inversely with GM volume in the right and left MI/SI and years of handball training experience correlated inversely with radial diffusivity in the right CST. Subcortical structures tended to be larger in handball players. The anatomical measures of the brain regions associated with handball playing were positively correlated in handball players, but not interrelated in control women. DISCUSSION/CONCLUSION: Training-induced structural alterations were found in the somatosensory-motor network of handball players, more pronounced in the right hemisphere controlling the non-dominant left hand. Correlations between handball training-related measures and anatomical differences suggest neuroplastic

Kai Lutz,1–3 Mario Widmer1,2,41Department of Neurology, University Hospital Zürich, Zürich, 2Cereneo, Center for Neurology and Rehabilitation, Vitznau, 3Division of Neuropsychology, Institute of Psychology, University of Zürich, Zürich, 4Neural Control of Movement Lab, ETH Zürich, Zürich, SwitzerlandAbstract: Since its introduction in 2000, the monetary incentive delay (MID) task has been used extensively to investigate changes in neural activity in response to the processing of reward and punishment in healthy, but also in clinical populations. Typically, the MID task requires an individual to react to a target stimulus presented after an incentive cue to win or to avoid losing the indicated reward. In doing so, this paradigm allows the detailed examination of different stages of reward processing like reward prediction, anticipation, outcome processing, and consumption as well as the processing of tasks under different reward conditions. This review gives an overview of different utilizations of the MID task by outlining the neuronal processes involved in distinct aspects of human reward processing, such as anticipation versus consumption, reward versus punishment, and, with a special focus, reward-based learning processes. Furthermore, literature on specific influences on reward processing like behavioral, clinical and developmental influences, is reviewed, describing current findings and possible future directions.Keywords: reward, punishment, dopamine, reward system