Faculty Bibliography

Movement is associated with power changes over sensory-motor areas in different frequency ranges, including beta (15-30 Hz). In fact, beta power starts decreasing before the movement onset (event-related desynchronization, ERD) and rebounds after its end (event-related synchronization, ERS). There is increasing evidence that beta modulation depth (measured as ERD-ERS difference) increases with practice in a planar reaching task, suggesting that this measure may reflect plasticity processes. In the present work, we analyzed beta ERD, ERS and modulation depth in healthy subjects to determine their changes over three regions of interest (ROIs): right and left sensorimotor and frontal areas, during a reaching task with the right arm. We found that ERD, ERS and modulation depth increased with practice with lower values over the right sensory-motor area. Timing of peak ERD and ERS were similar across ROIs, with ERS peak occurring earlier in later sets. Finally, we found that beta ERS of the frontal ROI involved higher beta range (23-29 Hz) than the sensory-motor ROIs (15-18 Hz). Altogether these results suggest that practice in a reaching task is associated with modification of beta power and timing. Additionally, beta ERS may have different functional meaning in the three ROIs, as suggested by the involvement of upper and lower beta bands in the frontal and sensorimotor ROIs, respectively.

During movement, modulation of beta power occurs over the sensorimotor areas, with a decrease just before its start (event-related desynchronization, ERD) and a rebound after its end (event-related synchronization, ERS). We have recently found that the depth of ERD-to-ERS modulation increases during practice in a reaching task and the following day decreases to baseline levels. Importantly, the magnitude of the beta modulation increase during practice is highly correlated with the retention of motor skill tested the following day. Together with other evidence, this suggests that the increase of practice-related modulation depth may be the expression of sensorimotor cortex's plasticity. Here, we determine whether the practice-related increase of beta modulation depth is equally present in a group of younger and a group of older subjects during the performance of a 30-minute block of reaching movements. We focused our analyses on two regions of interest (ROIs): the left sensorimotor and the frontal region. Performance indices were significantly different in the two groups, with the movements of older subjects being slower and less accurate. Importantly, both groups presented a similar increase of the practice-related beta modulation depth in both ROIs in the course of the task. Peak latency analysis revealed a progressive delay of the ERS peak that correlated with the total movement time. Altogether, these findings support the notion that the depth of beta modulation in a reaching movement task does not depend on age and confirm previous findings that only ERS peak latency but not ERS magnitude is related to performance indices.

Over the last decades, psychophysical and electrophysiological studies in patients and animal models of Parkinson's disease (PD), have consistently revealed a number of visual abnormalities. In particular, specific alterations of contrast sensitivity curves, electroretinogram (ERG), and visual-evoked potentials (VEP), have been attributed to dopaminergic retinal depletion. However, fundamental mechanisms of cortical visual processing, such as normalization or "gain control" computations, have not yet been examined in PD patients. Here, we measured electrophysiological indices of gain control in both space (surround suppression) and time (sensory adaptation) in PD patients based on steady-state VEP (ssVEP). Compared with controls, patients exhibited a significantly higher initial ssVEP amplitude that quickly decayed over time, and greater relative suppression of ssVEP amplitude as a function of surrounding stimulus contrast. Meanwhile, EEG frequency spectra were broadly elevated in patients relative to controls. Thus, contrary to what might be expected given the reduced contrast sensitivity often reported in PD, visual neural responses are not weaker; rather, they are initially larger but undergo an exaggerated degree of spatial and temporal gain control and are embedded within a greater background noise level. These differences may reflect cortical mechanisms that compensate for dysfunctional center-surround interactions at the retinal level.

Movement is accompanied by modulation of oscillatory activity in different ranges over the sensorimotor areas. This increase is more evident in normal subjects and less in patients with Parkinson's Disease (PD), a disorder associated with deficits in the formation of new motor skills. Here, we investigated whether such EEG changes improved in a group of PD patients, after two different treatments and whether this relates to performance. Subjects underwent either a session of 5 Hz repetitive Transcranial Magnetic Stimulation (rTMS) over the right posterior parietal cortex or a 4-week Multidisciplinary Intensive Rehabilitation Treatment (MIRT). We used a reaching task with visuo-motor adaptation to a rotated display in incremental 10° steps up to 60°. Retention of the learned rotation was tested before and after either intervention over two consecutive days. High-density EEG was recorded throughout the testing. We found that patients adapted their movements to the rotated display similarly to controls, although retention was poorer. Both rTMS and MIRT lead to improvement in retention of the learned rotation. Mean beta modulation levels changed significantly after MIRT and not after rTMS. These results suggest that rTMS produced local improvement reflected in enhanced short-term skill retention; on the other hand, MIRT determined changes across the contralateral sensorimotor area, reflected in beta EEG changes.

Cognitive impairment in Parkinson's disease (PD) is related to the reorganization of brain topology. Although drug challenge studies have proven how levodopa treatment can modulate functional connectivity in brain circuits, the role of chronic dopaminergic therapy on cognitive status and functional connectivity has never been investigated. We sought to characterize brain functional topology in mid-stage PD patients under chronic antiparkinson treatment and explore the presence of correlation between reorganization of brain architecture and specific cognitive deficits. We explored networks topology and functional connectivity in 16 patients with PD and 16 matched controls through a graph theoretical analysis of resting state-functional MRI data, and evaluated the relationships between network metrics and cognitive performance. PD patients showed a preserved small-world network topology but a lower clustering coefficient in comparison with healthy controls. Locally, PD patients showed lower degree of connectivity and local efficiency in many hubs corresponding to functionally relevant areas. Four disconnected subnetworks were also identified in regions responsible for executive control, sensory-motor control and planning, motor coordination and visual elaboration. Executive functions and information processing speed were directly correlated with degree of connectivity and local efficiency in frontal, parietal and occipital areas. While functional reorganization appears in both motor and cognitive areas, the clinical expression of network imbalance seems to be partially compensated by the chronic levodopa treatment with regards to the motor but not to the cognitive performance. In a context of reduced network segregation, the presence of higher local efficiency in hubs regions correlates with a better cognitive performance.

Though abnormalities of visuospatial function occur in Parkinson's disease, the impact of such deficits on functional independence and psychological wellbeing has been historically under- recognized, and effective treatments for this impairment are unknown. These symptoms can be encountered at any stage of the disease, affecting many activities of daily living, and negatively influencing mood, self-efficacy, independence, and overall quality of life. Furthermore, visuospatial dysfunction has been recently linked to gait impairment and falls, symptoms that are known to be poor prognostic factors. Here, we aim to present an original modality of neurorehabilitation designed to address visuospatial dysfunction and related symptoms in Parkinson's disease, known as "Art Therapy". Art creation relies on sophisticated neurologic mechanisms including shape recognition, motion perception, sensory-motor integration, abstraction, and eye-hand coordination. Furthermore, art therapy may enable subjects with disability to understand their emotions and express them through artistic creation and creative thinking, thus promoting self-awareness, relaxation, confidence and self-efficacy. The potential impact of this intervention on visuospatial dysfunction will be assessed by means of combined clinical, behavioral, gait kinematic, neuroimaging and eye tracking analyses. Potential favorable outcomes may drive further trials validating this novel paradigm of neurorehabilitation.

OBJECTIVE:To evaluate whether a 4-week multidisciplinary, aerobic, motor-cognitive and intensive rehabilitation treatment (MIRT) improves the quality of life (QoL) of patients with Parkinson's disease (PD), in the short-term and long-term period. METHODS:This is a prospective, parallel-group, single-centre, single-blind, randomised clinical trial (ClinicalTrials.gov NCT02756676). 186 patients with PD, assigned to experimental group, underwent MIRT; conversely, 48 patients, assigned to control group, did not receive rehabilitation. Parkinson's Disease Questionnaire-39 was assessed 2 (T0), 10 (T1) and 18 (T2, only experimental group) weeks after the enrolment. We compared T1 versus T0 scores within subjects and delta scores (T1-T0) between subjects. To investigate the long-term effects, we compared T2 and T0 scores in the experimental group. RESULTS:At T0, no between-group differences in the Global Index Score (GBI) were observed (experimental group: 43.6±21.4, controls: 41.6±22.9, P=0.50). At T1, we did not find significant changes in controls (delta score: 1.2±9.9, P=0.23), and we found an improvement in GBI in the experimental group (delta score: -8.3±18.0, P<0.0001), significant also between subjects (P<0.0001). Comparing T2 versus T0 in the experimental group, the GBI maintained a significant improvement (delta score: -4.8±17.5, P<0.0001). CONCLUSIONS:A rehabilitation treatment such as MIRT could improve QoL in patients with PD in the short-term and long-term period. Even though the single-blind design and the possible role of the placebo effect on the conclusive results must be considered as limitations of this study, the improvement in outcome measure, also maintained after a 3-month follow-up period, suggests the effectiveness of MIRT on the QoL. CLINICAL TRIAL REGISTRATION/BACKGROUND:NCT02756676: Pre-results.