.2010. In this study, we characterized the patterns and timing of cortical activation of visually guided movements in a task with critical temporal demands. In particular, we investigated the neural correlates of motor planning and on-line adjustments of reaching movements in a choice-reaction time task. High-density electroencephalograohy (EEG, 256 electrodes) was recorded in 13 subjects performing reaching movements. The topography of the movement-related spectral perturbation was established across five 250-ms temporal windows (from prestimulus to postmovement) and five frequency bands (from theta to beta). Nine regions of interest were then identified on the scalp, and their activity was correlated with specific behavioral outcomes reflecting motor planning and on-line adjustments. Phase coherence analysis was performed between selected sites. We found that motor planning and on-line adjustments share similar topography in a fronto-parietal network, involving mostly low frequency bands. In addition, activities in the high and low frequency ranges have differential function in the modulation of attention with the former reflecting the prestimulus, top-down processes needed to promote timely responses, and the latter the planning and control of sensory-motor processes.

The formation of new motor memories, which is fundamental for efficient performance during adaptation to a visuo-motor rotation, occurs when accurate planning is achieved mostly with feedforward mechanisms. The dynamics of brain activity underlying the switch from feedback to feedforward control is still matter of debate. Based upon the results of studies in declarative learning, it is likely that phase synchronization of low and high frequencies as well as their temporal modulation in power amplitude underlie the formation of new motor memories during visuo-motor adaptation. High density-EEG (256 electrodes) was recorded in 17 normal human subjects during adaptation to a visuo-motor rotation of 60° in four incremental steps of 15°. We found that initial learning is associated with enhancement of gamma power in a right parietal region during movement execution as well as gamma/theta phase coherence during movement planning. Late stages of learning are instead accompanied by an increase of theta power over that same right parietal region during movement planning, which is correlated with the degree of learning and retention. Altogether, these results suggest that the formation of new motor memories and thus, the switch from feedback to feedforward control, is associated with the modulation of gamma and theta spectral activities, with respect to their amplitude and phase, during movement planning and execution. Specifically, we propose that gamma/theta phase coupling plays a pivotal role in the integration of a new representation into motor memories.

BACKGROUND In a combined animal and human study, we have previously found that a five-day treatment that enhances cortical plasticity also facilitates brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling and increases activated TrkB and N-methyl-D-aspartate receptor (NMDAR) association in both the cortex and the peripheral lymphocytes. Patients with Parkinson’s disease (PD) in general show decreased cortical plasticity, as demonstrated by electrophysiological and behavioral studies. Here we test the hypothesis that an exercise program that improves motor function and seems to slow down symptoms’ progression can enhance BDNF-TrkB signaling in lymphocytes. METHODS Sixteen patients with PD underwent a four-week Multidisciplinary Intensive Rehabilitation Treatment (MIRT), which included aerobic training, physical and occupational therapy. Blood was collected before, after two- and four-week MIRT. Lymphocytes were isolated to examine BDNF-TrkB signaling induced by incubation with recombinant human BDNF. TrkB signaling complexes, extracellular-signal-regulated kinase-2 and protein-kinase-B were immunoprecipitated; content of immunocomplexes was determined by Western blotting. RESULTS After MIRT, all patients showed improvement in motor function. TrkB interaction with NMDAR and BDNF-TrkB signaling increased in peripheral lymphocytes at receptor, intracellular mediators and downstream levels. The decrements in UPDRSII and total scores were significantly correlated with the increases in TrkB signaling at receptor, intracellular mediators and NMDAR interaction levels. CONCLUSIONS The significant correlation between reduced UPDRS scores and the changes in lymphocytes’ activity suggest that enhanced BDNF-TrkB signaling in lymphocyte and reduced severity of PD symptoms may be related.

Purpose To pool data across multiple institutions internationally and report on the cumulative experience of brainstem stereotactic radiosurgery (SRS). Methods and Materials Data on patients with brainstem metastases treated with SRS were collected through the International Gamma Knife Research Foundation. Clinical, radiographic, and dosimetric characteristics were compared for factors prognostic for local control (LC) and overall survival (OS) using univariate and multivariate analyses. Results Of 547 patients with 596 brainstem metastases treated with SRS, treatment of 7.4% of tumors resulted in severe SRS-induced toxicity (grade ≥3, increased odds with increasing tumor volume, margin dose, and whole-brain irradiation). Local control at 12 months after SRS was 81.8% and was improved with increasing margin dose and maximum dose. Overall survival at 12 months after SRS was 32.7% and impacted by age, gender, number of metastases, tumor histology, and performance score. Conclusions Our study provides additional evidence that SRS has become an option for patients with brainstem metastases, with an excellent benefit-to-risk ratio in the hands of experienced clinicians. Prior whole-brain irradiation increases the risk of severe toxicity in brainstem metastasis patients undergoing SRS.