Modulation of neural activity in frontopolar cortex drives reward-based motor learning.

The frontopolar cortex (FPC) contributes to tracking the reward of alternative choices during decision making, as well as their reliability. Whether this FPC function extends to reward gradients associated with continuous movements during motor learning remains unknown. We used anodal transcranial direct current stimulation (tDCS) over the right FPC to investigate its role in reward-based motor learning. Nineteen healthy human participants practiced novel sequences of finger movements on a digital piano with corresponding auditory feedback. Their aim was to use trialwise reward feedback to discover a hidden performance goal along a continuous dimension: timing. We additionally modulated the contralateral motor cortex (left M1) activity, and included a control sham stimulation. Right FPC-tDCS led to faster learning compared to lM1-tDCS and sham through regulation of motor variability. Bayesian computational modelling revealed that in all stimulation protocols, an increase in the trialwise expectation of reward was followed by greater exploitation, as shown previously. Yet, this association was weaker in lM1-tDCS suggesting a less efficient learning strategy. The effects of frontopolar stimulation were dissociated from those induced by lM1-tDCS and sham, as motor exploration was more sensitive to inferred changes in the reward tendency (volatility). The findings suggest that rFPC-tDCS increases the sensitivity of motor exploration to updates in reward volatility, accelerating reward-based motor learning.

Impairment of emotional facial expression and prosody discrimination due to ischemic cerebellar lesions.

A growing literature points to a specific role of the cerebellum in affect processing. However, understanding of affect processing disturbances following discrete cerebellar lesions is limited. We administered the Tübingen Affect Battery to assess recognition of emotional facial expression and emotional prosody in 15 patients with a cerebellar infarction and 10 age-matched controls. On emotional facial expression tasks, patients compared to controls showed impaired selection and matching of facial affect. On prosody tasks, patients showed marked impairments in naming affect and discriminating incongruencies. These deficits were more pronounced for negative affects. Our results confirm a significant role of the cerebellum in processing emotional recognition, a component of social cognition.

Functional neuroanatomy of mirroring during a unimanual force generation task.

Performance of a unimanual motor task often induces involuntary mirror electromyographic (EMG) activity in the opposite, resting hand. In spite of the ubiquitous presence of mirroring, little is known regarding the underlying cortical contributions. Here, we used functional magnetic resonance imaging (fMRI) to study brain regions activated in association with parametric increases in right isometric wrist flexion force (10%, 20%, 30%, and 70%) in 12 healthy volunteers. During scanning, EMG activity was recorded bilaterally from flexor carpi radialis (FCR), extensor carpi radialis (ECR), biceps brachii (BB), and triceps brachii (TB). Mirror EMG was observed in left FCR during 20%, 30%, and 70% of force. Left ECR, BB, and TB showed mirror EMG only at 70% of force. Increasing force was associated with a linear increase of blood-oxygen-level-dependent (BOLD) signal in bilateral primary motor cortex (M1), supplementary motor area (SMA), caudal cingulate, and cerebellum. Mirroring in the left FCR correlated with activity in bilateral M1, SMA, and the cerebellum. Overall, our results suggest that activity in these regions might reflect sensorimotor processes operating in association with mirroring and suggest caution when interpreting fMRI activity in studies that involve unilateral force generation tasks in the absence of simultaneous bilateral EMG/kinematics measurements.

Investigation of arthritic joint destruction by a novel fibroblast-based model.

The key pathologic mechanism in rheumatoid arthritis (RA) is the destruction of cartilage by fibroblasts. In a severe combined immunodeficient (SCID) mouse model, this process can be modulated by gene transfer using invasive LS48 fibroblasts. This study aims to investigate the effect of interleukins (IL) -11 and -12 on cartilage destruction when transferred into LS48, and of IL-15 when transfected into non-invasive 3T3 cells; to compare three transduction systems (a lentiviral vector system, a retroviral vector system, and a particle-mediated gene transfer); and to establish an in vitro cartilage destruction system based on LS48 cells. Transduced fibroblasts were injected into SCID mice knee joints, and disease progression assessed microscopically. Distinctive morphologic pattern revealed invasion of fibroblasts into the articular cartilage by transfected, as well as non-transfected, LS48 cells. IL-12 and IL-15 did not alter swelling or cartilage destruction. Animals treated with IL-11-transfected cells showed reduced cartilage damage but no changes in swelling. Efficacy of gene transfer to establish transfected fibroblasts was shown to be >85% for lentiviral transfer, compared to <10% for retroviral transfer and gene gun. Furthermore, cells were co-incubated with porcine cartilage. Transduction of IL-11 led to a reduction of apoptosis in chondrocytes. These findings suggest that cartilage destruction by invasive fibroblasts can be modulated by gene transfer. Lentiviral vector systems offer the most effective approach for gene transduction. In vitro fibroblast/cartilage co-cultures present a convenient system for the assessment of novel therapeutic strategies toward reduction of articular destruction.