@article{DipaolaPavanCattaneoetal.2016, author = {Dipaola, Mariangela and Pavan, Esteban E. and Cattaneo, Andrea and Frazzitta, Giuseppe and Pezzoli, Gianni and Cavallari, Paolo and Frigo, Carlo A. and Isaias, Ioannis U.}, title = {Mechanical Energy Recovery during Walking in Patients with Parkinson Disease}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0156420}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179739}, year = {2016}, abstract = {The mechanisms of mechanical energy recovery during gait have been thoroughly investigated in healthy subjects, but never described in patients with Parkinson disease (PD). The aim of this study was to investigate whether such mechanisms are preserved in PD patients despite an altered pattern of locomotion. We consecutively enrolled 23 PD patients (mean age 64±9 years) with bilateral symptoms (H\&Y ≥II) if able to walk unassisted in medication-off condition (overnight suspension of all dopaminergic drugs). Ten healthy subjects (mean age 62±3 years) walked both at their 'preferred' and 'slow' speeds, to match the whole range of PD velocities. Kinematic data were recorded by means of an optoelectronic motion analyzer. For each stride we computed spatio-temporal parameters, time-course and range of motion (ROM) of hip, knee and ankle joint angles. We also measured kinetic (Wk), potential (W\(_{p}\)), total (W\(_{totCM}\)) energy variations and the energy recovery index (ER). Along with PD progression, we found a significant correlation of W\(_{totCM}\) and W\(_{p}\) with knee ROM and in particular with knee extension in terminal stance phase. W\(_{k}\) and ER were instead mainly related to gait velocity. In PD subjects, the reduction of knee ROM significantly diminished both W\(_{p}\) and W\(_{totCM}\). Rehabilitation treatments should possibly integrate passive and active mobilization of knee to prevent a reduction of gait-related energetic components.}, language = {en} } @phdthesis{Palmisano2022, author = {Palmisano, Chiara}, title = {Supraspinal Locomotor Network Derangements: A Multimodal Approach}, doi = {10.25972/OPUS-26644}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266442}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Parkinson's Disease (PD) constitutes a major healthcare burden in Europe. Accounting for aging alone, ~700,000 PD cases are predicted by 2040. This represents an approximately 56\% increase in the PD population between 2005 and 2040, with a consequent rise in annual disease-related medical costs. Gait and balance disorders are a major problem for patients with PD and their caregivers, mainly because to their correlation with falls. Falls occur as a result of a complex interaction of risk factors. Among them, Freezing of Gait (FoG) is a peculiar gait derangement characterized by a sudden and episodic inability to produce effective stepping, causing falls, mobility restrictions, poor quality of life, and increased morbidity and mortality. Between 50-70\% of PD patients have FoG and/or falls after a disease duration of 10 years, only partially and inconsistently improved by dopaminergic treatment and Deep Brain Stimulation (DBS). Treatment-induced worsening has been also observed under certain conditions. Effective treatments for gait disturbances in PD are lacking, probably because of the still poor understanding of the supraspinal locomotor network. In my thesis, I wanted to expand our knowledge of the supraspinal locomotor network and in particular the contribution of the basal ganglia to the control of locomotion. I believe this is a key step towards new preventive and personalized therapies for postural and gait problems in patients with PD and related disorders. In addition to patients with PD, my studies also included people affected by Progressive Supranuclear Palsy (PSP). PSP is a rare primary progressive parkinsonism characterized at a very early disease stage by poor balance control and frequent backwards falls, thus providing an in vivo model of dysfunctional locomotor control. I focused my attention on one of the most common motor transitions in daily living, the initiation of gait (GI). GI is an interesting motor task and a relevant paradigm to address balance and gait impairments in patients with movement disorders, as it is associated with FoG and high risk of falls. It combines a preparatory (i.e., the Anticipatory Postural Adjustments [APA]) and execution phase (the stepping) and allows the study of movement scaling and timing as an expression of muscular synergies, which follow precise and online feedback information processing and integration into established feedforward patterns of motor control. By applying a multimodal approach that combines biomechanical assessments and neuroimaging investigations, my work unveiled the fundamental contribution of striatal dopamine to GI in patients with PD. Results in patients with PSP further supported the fundamental role of the striatum in GI execution, revealing correlations between the metabolic intake of the left caudate nucleus with diverse GI measurements. This study also unveiled the interplay of additional brain areas in the motor control of GI, namely the Thalamus, the Supplementary Motor Area (SMA), and the Cingulate cortex. Involvement of cortical areas was also suggested by the analysis of GI in patients with PD and FoG. Indeed, I found major alterations in the preparatory phase of GI in these patients, possibly resulting from FoG-related deficits of the SMA. Alterations of the weight shifting preceding the stepping phase were also particularly important in PD patients with FoG, thus suggesting specific difficulties in the integration of somatosensory information at a cortical level. Of note, all patients with PD showed preserved movement timing of GI, possibly suggesting preserved and compensatory activity of the cerebellum. Postural abnormalities (i.e., increased trunk and thigh flexion) showed no relationship with GI, ruling out an adaptation of the motor pattern to the altered postural condition. In a group of PD patients implanted with DBS, I further explored the pathophysiological functioning of the locomotor network by analysing the timely activity of the Subthalamic Nucleus (STN) during static and dynamic balance control (i.e., standing and walking). For this study, I used novel DBS devices capable of delivering stimulation and simultaneously recording Local Field Potentials (LFP) of the implanted nucleus months and years after surgery. I showed a gait-related frequency shift in the STN activity of PD patients, possibly conveying cortical (feedforward) and cerebellar (feedback) information to mesencephalic locomotor areas. Based on this result, I identified for each patient a Maximally Informative Frequency (MIF) whose power changes can reliably classify standing and walking conditions. The MIF is a promising input signal for new DBS devices that can monitor LFP power modulations to timely adjust the stimulation delivery based on the ongoing motor task (e.g., gait) performed by the patient (adaptive DBS). Altogether my achievements allowed to define the role of different cortical and subcortical brain areas in locomotor control, paving the way for a better understanding of the pathophysiological dynamics of the supraspinal locomotor network and the development of tailored therapies for gait disturbances and falls prevention in PD and related disorders.}, language = {en} } @article{PalmisanoKullmannHanafietal.2022, author = {Palmisano, Chiara and Kullmann, Peter and Hanafi, Ibrahem and Verrecchia, Marta and Latoschik, Marc Erich and Canessa, Andrea and Fischbach, Martin and Isaias, Ioannis Ugo}, title = {A fully-immersive virtual reality setup to study gait modulation}, series = {Frontiers in Human Neuroscience}, volume = {16}, journal = {Frontiers in Human Neuroscience}, issn = {1662-5161}, doi = {10.3389/fnhum.2022.783452}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267099}, year = {2022}, abstract = {Objective: Gait adaptation to environmental challenges is fundamental for independent and safe community ambulation. The possibility of precisely studying gait modulation using standardized protocols of gait analysis closely resembling everyday life scenarios is still an unmet need. Methods: We have developed a fully-immersive virtual reality (VR) environment where subjects have to adjust their walking pattern to avoid collision with a virtual agent (VA) crossing their gait trajectory. We collected kinematic data of 12 healthy young subjects walking in real world (RW) and in the VR environment, both with (VR/A+) and without (VR/A-) the VA perturbation. The VR environment closely resembled the RW scenario of the gait laboratory. To ensure standardization of the obstacle presentation the starting time speed and trajectory of the VA were defined using the kinematics of the participant as detected online during each walking trial. Results: We did not observe kinematic differences between walking in RW and VR/A-, suggesting that our VR environment per se might not induce significant changes in the locomotor pattern. When facing the VA all subjects consistently reduced stride length and velocity while increasing stride duration. Trunk inclination and mediolateral trajectory deviation also facilitated avoidance of the obstacle. Conclusions: This proof-of-concept study shows that our VR/A+ paradigm effectively induced a timely gait modulation in a standardized immersive and realistic scenario. This protocol could be a powerful research tool to study gait modulation and its derangements in relation to aging and clinical conditions.}, language = {en} }