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Background and Aims: Functional motor disorders (FMD) present a prevalent, yet misunderstood spectrum of neurological conditions characterized by abnormal movements (i.e., functional limb weakness, tremor, dystonia, gait impairments), leading to substantial disability and diminished quality of life. Despite their high prevalence, FMD often face delayed diagnosis and inadequate treatment, resulting in significant social and economic burdens. The old concept of psychological factors as the primary cause (conversion disorder) has been abandoned due to the need for more evidence about their causal role. According to a predictive coding account, the emerging idea is that symptoms and disability may depend on dysfunctions of a specific neural system integrating interoception, exteroception, and motor control. Consequently, symptoms are construed as perceptions of the body's state. Besides the main pathophysiological features (abnormal attentional focus, beliefs/expectations, and sense of agency), the lived experience of symptoms and their resulting disability may depend on an altered integration at the neural level of interoception, exteroception, and motor control., Methods and Materials: Our proposal aims to elucidate the pathophysiological mechanisms of FMD through a three-stage research approach. Initially, a large cohort study will collect behavioral, neurophysiological, and MRI biomarkers from patients with FMD and healthy controls, employing eXplainable Artificial Intelligence (XAI) to develop a diagnostic algorithm. Subsequently, validation will occur using patients with organic motor disorders. Finally, the algorithm's prognostic value will be explored post-rehabilitation in one subgroup of patients with FMD., Results: Data collection for the present study started in May 2023, and by May 2025, data collection will conclude., Discussion: Our approach seeks to enhance early diagnosis and prognostication, improve FMD management, and reduce associated disability and socio-economic costs by identifying disease-specific biomarkers., Trial Registration: This trial was registered in clinicaltrials.gov (NCT06328790)., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: E. Sarasso and E. Canu have received research support from the Italian Ministry of Health. M. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology, received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi, speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA, participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda, scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme, he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla. F. Agosta is Associate Editor of NeuroImage: Clinical, has received speaker honoraria from Biogen Idec, Italfarmaco, Roche, Zambon and Ely Lilli, and receives or has received research supports from the Italian Ministry of Health, the Italian Ministry of University and Research, AriSLA (Fondazione Italiana di Ricerca per la SLA), the European Research Council, the EU Joint Programme – Neurodegenerative Disease Research (JPND), and Foundation Research on Alzheimer Disease (France). The other authors have declared that no competing interests exist., (Copyright: © 2024 Gandolfi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bradykinesia is defined as a "complex" of motor alterations including decreased movement amplitude and/or speed and tendency to reduce them with movement repetition (sequence effect). This study aimed at investigating the neural and kinematic correlates of bradykinesia during hand-tapping in people with Parkinson's disease (pwPD) relative to healthy controls. Twenty-five pwPD and 25 age- and sex-matched healthy controls underwent brain functional MRI (fMRI) during a hand-tapping task: subjects alternatively opened and closed their right hand as fully and quickly as possible. Hand-tapping kinematic parameters were objectively measured during the fMRI task using an optical fibre glove. During the fMRI task, pwPD showed reduced hand-tapping amplitude (hypokinesia) and a greater sequence effect. PwPD relative to healthy controls showed a reduced activity of fronto-parietal areas, middle cingulum/supplementary motor area (SMA), parahippocampus, pallidum/thalamus and motor cerebellar areas. Moreover, pwPD showed an increased activity of brain cognitive areas such as superior temporal gyrus, posterior cingulum, and cerebellum crus I. The decreased activity of cerebellum IV-V-VI, vermis IV-V, inferior frontal gyrus, and cingulum/SMA correlated with hypokinesia and with the sequence effect. Interestingly, a reduced activity of areas involved in motor planning and timing correlated both with hypokinesia and with the sequence effect in pwPD. This study has the major strength of collecting objective motor parameters and brain activity simultaneously, providing a unique opportunity to investigate the neural correlates of the "bradykinesia complex"., (© 2024. The Author(s).)

Background: Isolated rapid eye movement sleep behavioral disorder (iRBD) can precede neurodegenerative diseases. There is an urgent need for biomarkers to aid early intervention and neuroprotection., Objective: The aim is to assess quantitative motor, cognitive, and brain magnetic resonance imaging (MRI) characteristics in iRBD patients., Methods: Thirty-eight polysomnography-confirmed iRBD patients and 28 age- and sex-matched healthy controls underwent clinical, cognitive, and motor functional evaluations, along with brain MRI. Motor tasks included nine-hole peg test, five-times-sit-to-stand test, timed-up-and-go test, and 4-meter walking test with and without cognitive dual task. Quantitative spatiotemporal gait parameters were obtained using an optoelectronic system. Brain MRI analysis included functional connectivity (FC) of the main resting-state networks, gray matter (GM) volume using voxel-based morphometry, cortical thickness, and deep GM and brainstem volumes using FMRIB's Integrated Registration and Segmentation Tool and FreeSurfer., Results: iRBD patients relative to healthy subjects exhibited a poorer performance during the nine-hole peg test and five-times-sit-to-stand test, and greater asymmetry of arm-swing amplitude and stride length variability during dual-task gait. Dual task significantly worsened the walking performance of iRBD patients more than healthy controls. iRBD patients exhibited nonmotor symptoms, and memory, abstract reasoning, and visuospatial deficits. iRBD patients exhibited decreased FC of pallidum and putamen within the basal ganglia network and occipital and temporal areas within the visuo-associative network, and a reduced volume of the supramarginal gyrus. Brain functional alterations correlated with gait changes., Conclusions: Subtle motor and nonmotor alterations were identified in iRBD patients, alongside brain structural and functional MRI changes. These findings may represent early signs of neurodegeneration and contribute to the development of predictive models for progression to parkinsonism. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Introduction: Evaluating the neural correlates of sensorimotor control deficits in cervical dystonia (CD) is fundamental to plan the best treatment. This study aims to assess kinematic and resting-state functional connectivity (RS-FC) characteristics in CD patients relative to healthy controls., Methods: Seventeen CD patients and 14 age-/sex-matched healthy controls were recruited. Electromagnetic sensors were used to evaluate dystonic pattern, mean/maximal cervical movement amplitude and joint position error with eyes open and closed, and movement quality during target reaching with the head. RS-fMRI was acquired to compare the FC of brain sensorimotor regions between patients and controls. In patients, correlations between motion analysis and FC data were assessed., Results: CD patients relative to controls showed reduced mean and maximal cervical range of motion (RoM) in rotation both towards and against dystonia pattern and reduced total RoM in rotation both with eyes open and closed. They had less severe dystonia pattern with eyes open vs eyes closed. CD patients showed an altered movement quality and sensorimotor control during target reaching and a higher joint position error. Compared to controls, CD patients showed reduced FC between supplementary motor area (SMA), occipital and cerebellar areas, which correlated with lower cervical RoM in rotation both with eyes open and closed and with worse movement quality during target reaching., Conclusions: FC alterations between SMA and occipital and cerebellar areas may represent the neural basis of cervical sensorimotor control deficits in CD patients. Electromagnetic sensors and RS-fMRI might be promising tools to monitor CD and assess the efficacy of rehabilitative interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elisabetta Sarasso reports a relationship with Italian Ministry of Health that includes: funding grants. Daniele Emedoli reports a relationship with Khymeia Group S.R.L that includes: consulting or advisory and speaking and lecture fees. Andrea Gardoni reports a relationship with none that includes:. Lucia Zenere reports a relationship with None that includes:. Elisa Canu reports a relationship with Italian Ministry of Health that includes: funding grants. Silvia Basaia reports a relationship with Italian Ministry of Health that includes: funding grants. Alberto Doretti reports a relationship with AbbVie Inc, Eli Lilly, TEVA, Lundbeck that includes: consulting or advisory. Nicola Ticozzi reports a relationship with None that includes:. Sandro Iannaccone reports a relationship with None that includes:. Stefano Amadio reports a relationship with None that includes:. Ubaldo Del Carro reports a relationship with None that includes:. Massimo Filippi reports a relationship with Alexion, Almirall, Bayer, Biogen, BMS, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, TEVA, Italian Ministry of Health, Italian Ministry of University and Research, FISM that includes: consulting or advisory, funding grants, and speaking and lecture fees. Federica Agosta reports a relationship with Biogen Idec, Italfarmaco, Roche, Zambon, Ely Lilli, Italian Ministry of Health, Italian Ministry of University and Research, AriSLA, the European Research Council, the EU JPND, and Foundation Research on Alzheimer Disease (France) that includes: funding grants and speaking and lecture fees. M. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology; F. Agosta is Associate Editor of NeuroImage: Clinical If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Motor imagery (MI) skills can be affected in Parkinson's disease (PD). We aimed at assessing MI and brain functional changes after action observation and MI training (AOT-MI) associated with gait/balance exercises in PD patients with postural instability and gait disorders (PD-PIGD)., Methods: Twenty-five PD-PIGD patients were randomized into two groups: DUAL-TASK + AOT-MI group performed 6-week gait/balance training combined with AOT-MI; DUAL-TASK group performed the same exercises without AOT-MI. Before and after training, MI was assessed using Kinesthetic-and-Visual-Imagery Questionnaire (KVIQ) and a MI functional MRI (fMRI) task. During fMRI, subjects were asked to watch first-person perspective videos representing gait/balance tasks and mentally simulate their execution. At baseline patients were compared with 23 healthy controls., Results: PD groups did not differ in the MI scores. Both patient groups increased kinesthetic KVIQ score after training, while only DUAL-TASK + AOT-MI group improved visual and total KVIQ scores. At baseline, both PD groups showed reduced fMRI activity of sensorimotor, temporal and cerebellar areas relative to controls. After training, DUAL-TASK + AOT-MI patients increased activity of anterior cingulate, fronto-temporal and motor cerebellar areas, and reduced the recruitment of cognitive cerebellar regions. DUAL-TASK group showed increased recruitment of occipito-temporal areas and reduced activity of cerebellum crus-I. DUAL-TASK + AOT-MI relative to DUAL-TASK group had increased activity of cerebellum VIII-IX. In DUAL-TASK + AOT-MI group, KVIQ improvement correlated with increased activity of cerebellum IX and anterior cingulate, and with reduced activity of crus-I., Conclusions: AOT-MI improves MI abilities in PD-PIGD patients, promoting the functional plasticity of brain areas involved in MI processes and gait/balance control., (Copyright © 2023 Elsevier Ltd. All rights reserved.)