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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., Tremor is defined as a rhythmic, involuntary oscillatory movement of a body part. Although everyone exhibits a certain degree of tremor, some pathologies lead to very disabling tremors. These pathological tremors constitute the most prevalent movement disorder, and they imply severe difficulties in performing activities of daily living. Although tremors are currently managed through pharmacotherapy or surgery, these treatments present significant associated drawbacks: drugs often induce side effects and show decreased effectiveness over years of use, while surgery is a hazardous procedure for a very low percentage of eligible patients. In this context, recent research demonstrated the feasibility of managing upper limb tremors through wearable technologies that suppress tremors by modifying limb biomechanics or applying counteracting forces. Furthermore, recent experiments with transcutaneous afferent stimulation showed significant tremor attenuation. In this regard, this article reviews the devices developed following these tremor management paradigms, such as robotic exoskeletons, soft robotic exoskeletons, and transcutaneous neurostimulators. These works are presented, and their effectiveness is discussed. The article also evaluates the different metrics used for the validation of these devices and the lack of a standard validation procedure that allows the comparison among them., This research was funded by Spanish Ministry of Science and Innovation, project Discover2Walk (PID2019-105110RBC31). JL-M received a Training Program for Academic Staff fellowship (FPU16/01313) from the Ministry of Universities of the Government of Spain. GD-O received an international postgraduate scholarship from Secretaria Nacional de Educación Superior, Ciencia, Tecnología e Innovación of Ecuador (SENESCYT). We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).

Essential tremor (ET) is a neurological disease with both motor and nonmotor manifestations; however, little is known about its underlying brain basis. Furthermore, the overall organization of the brain network in ET remains largely unexplored. We investigated the topological properties of brain functional network, derived from resting¿state functional magnetic resonance imaging (MRI) data, in 23 ET patients versus 23 healthy controls. Graph theory analysis was used to assess the functional network organization. At the global level, the functional network of ET patients was characterized by lower small¿worldness values than healthy controls¿less clustered functionality of the brain. At the regional level, compared with the healthy controls, ET patients showed significantly higher values of global efficiency, cost and degree, and a shorter average path length in the left inferior frontal gyrus (pars opercularis), right inferior temporal gyrus (posterior division and temporo¿occipital part), right inferior lateral occipital cortex, left paracingulate, bilateral precuneus bilaterally, left lingual gyrus, right hippocampus, left amygdala, nucleus accumbens bilaterally, and left middle temporal gyrus (posterior part). In addition, ET patients showed significant higher local efficiency and clustering coefficient values in frontal medial cortex bilaterally, subcallosal cortex, posterior cingulate cortex, parahippocampal gyri bilaterally (posterior division), right lingual gyrus, right cerebellar flocculus, right postcentral gyrus, right inferior semilunar lobule of cerebellum and culmen of vermis. Finally, the right intracalcarine cortex and the left orbitofrontal cortex showed a shorter average path length in ET patients, while the left frontal operculum and the right planum polare showed a higher betweenness centrality in ET patients. In conclusion, the efficiency of the overall brain functional network in ET is disrupted. Further, our results support the concept that ET is a disorder that disrupts widespread brain regions, including those outside of the brain regions responsible for tremor., Spanish Ministry of Economy and Competitiveness, Grant/Award Number: DPI‐2015‐72638‐EXP; European Commission, Grant/Award Number: ICT‐2011‐287739; Spanish Ministry of Economy and Competitiveness, Grant/Award Number: DPI‐2015‐68664‐C4‐1‐R; Claire O'Neil Essential Tremor Research Fund; Spanish Health Research Agency, Grant/Award Numbers: FIS PI16/00451, FIS PI12/01602; Ministry of Economy and Competitiveness, Grant/Award Number: RTC‐2015‐3967‐1; National Institutes of Health, Grant/Award Numbers: NINDS #R01 NS088257, NINDS #R01 NS073872, NINDS #R01 NS085136, NINDS #R01 NS094607, NINDS #R01 NS39422, Sí

Objective: Oculomotor tasks can be used to measure volitional control of behavior sensitive to frontal dysfunction. This study aimed to examine the saccadic eye movement in Genetic Generalized Epilepsy (GGE) which could correlate with the abnormality of the frontal lobe or the thalamo-frontal network. Methods: Twenty-one patients with GGE were compared with 22 patients with Temporal Lobe Epilepsy (TLE) and 39 healthy controls. Visual-guided saccades, Antisaccades, and Memory-guided saccades as oculomotor tasks were performed using a novel gaze-tracker designed for clinical practice use. Results: Patients with epilepsy (either GEE or TLE) had similar latency, accuracy, and velocity in visual-guided saccades and memory-guided saccades. Patients with epilepsy had similar latencies and correct antisaccade number. However, healthy volunteers, matched by age, had faster responses and more accurate results than patients with epilepsy. Conclusions: Our investigations did not reveal differences between TLE and GGE patients' groups in visually guided saccades, antisaccades, and memory-guided saccades, thus suggesting that the frontal cortical mechanisms responsible for them are not explicitly impaired in patients with GGE.

Wearable technology used in Parkinson's disease (PD) research has become an increasing focus of interest in this field. Our group assessed the feasibility, clinical correlation, reliability, and acceptance of smartwatches in order to quantify arm resting tremors in PD patients. An Android application on a smartwatch was used to obtain raw data from the smartwatch's gyroscopes. Twenty-two PD patients were consecutively recruited and followed for 1 year. Arm rest tremors were video filmed and scored by two independent raters using the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS-III). The tremor intensity parameter was defined by the root mean square of the angular speed measured by the smartwatch at the wrist. Sixty-four smartwatch evaluations were completed. The Spearman coefficient among the mean of the resting tremor (UPDRS-III) scores and smartwatch measurements for tremor intensity was 0.81 (p, This work was supported by the Ministerio de Economía y Competitividad, Gobierno de España [RTC-2015-3967-1, “NetMD - Plataforma para el seguimiento de Trastornos del Movimiento”].

Orthostatic tremor (OT) is an extremely rare, misdiagnosed, and underdiagnosed disorder affecting adults in midlife. There is debate as to whether it is a different condition or a variant of essential tremor (ET), or even, if both conditions coexist. Our objective was to use data mining classification methods, using magnetic resonance imaging (MRI)-derived brain volume and cortical thickness data, to identify morphometric measures that help to discriminate OT patients from those with ET. Methods: MRI-derived brain volume and cortical thickness were obtained from 14 OT patients and 15 age-, sex-, and education-matched ET patients. Feature selection and machine learning methods were subsequently applied. Results: Four MRI features alone distinguished the two, OT from ET, with 100% diagnostic accuracy. More specifically, left thalamus proper volume (normalized by the total intracranial volume), right superior parietal volume, right superior parietal thickness, and right inferior parietal roughness (i.e., the standard deviation of cortical thickness) were shown to play a key role in OT and ET characterization. Finally, the left caudal anterior cingulate thickness and the left caudal middle frontal roughness allowed us to separate with 100% diagnostic accuracy subgroups of OT patients (primary and those with mild parkinsonian signs). Conclusions: A data mining approach applied to MRI-derived brain volume and cortical thickness data may differentiate between these two types of tremor with an accuracy of 100%. Our results suggest that OT and ET are distinct conditions., This research was supported by FEDER funds. Benito‐León is supported by the National Institutes of Health, Bethesda, MD, USA (NINDS #R01 NS39422), European Commission (grant ICT‐2011‐287739, NeuroTREMOR), the Ministry of Economy and Competitiveness (grant RTC‐2015‐3967‐1, NetMD – platform for the tracking of movement disorder), and the Spanish Health Research Agency (grant FIS PI12/01602 and grant FIS PI16/00451). Romero is supported by the European Commission (grant ICT‐2011‐287739, NeuroTREMOR) and the Spanish Ministry of Economy and Competitiveness (grant DPI‐2015‐68664‐C4‐1‐R, NeuroMOD). Louis has received research support from the National Institutes of Health: NINDS #R01 NS094607 (principal investigator), NINDS #R01 NS085136 (principal investigator), NINDS #R01 NS073872 (principal investigator), NINDS #R01 NS085136 (principal investigator), and NINDS #R01 NS088257 (principal investigator). He has also received support from the Claire O'Neil Essential Tremor Research Fund (Yale University). Sánchez‐Ferro is supported by the Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid and the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007‐2013). Serrano is supported by RoboCity2030‐DIH‐CM Madrid Robotics Digital Innovation Hub (“Robótica aplicada a la mejora de la calidad de vida de los ciudadanos. fase IV”; S2018/NMT‐4331), funded by “Programas de Actividades I + D en la Comunidad de Madrid” and cofunded by Structural Funds of the European Commission. We acknowledge the neuropsychologist Verónica Puertas‐Martín, for her assistance with the project.

Background The Neurological Disorders in Central Spain, second survey (NEDICES-2) is a population-based, closed-cohort study that will include over 8000 subjects aged ≥55 years. It will also include a biobank. Objective The objective of this study was to evaluate all major aspects of the NEDICES-2 (methods, database, screening instruments, and questionnaires, as well as interexpert rating of the neurological diagnoses) in each one of the planned areas (all of them in central Spain) and to test the possibility of obtaining biological samples from each participant. Methods A selection of patients and participants of the planned NEDICES-2 underwent face-to-face interviews including a comprehensive questionnaire on demographics, current medications, medical conditions, and lifestyle habits. Biological samples (blood, saliva, urine, and hair) were also obtained. Furthermore, every participant was examined by a neurologist. Results In this pilot study, 567 study participants were enrolled (196 from hospitals and 371 from primary care physician lists). Of these 567, 310 completed all study procedures (questionnaires and the neurological evaluation). The study was time-consuming for several primary care physicians. Hence, a few primary care physicians from some areas refused to participate, which led to a reconfiguration of study areas. In addition, the central biobank needed to be supplemented by the biobanks of local Spanish National Health System hospitals. Conclusions Population-based epidemiological surveys, such as the NEDICES-2, require a pilot study to evaluate the feasibility of all aspects of a future field study (population selection, methods and instruments to be used, neurological diagnosis agreement, and data collection)., Our thanks to all collaborators in this feasibility pilot study, the Instituto de Salud Carlos III and the Biomedical Research Networking Center on Neurodegenerative Diseases (CIBERNED), and the two hospital computer experts (Victoria Garcia Baquero and Teresa Garcia Morales), who created the website (http://nedices2.ciberned.com/estudio-de-salud-nedices-2/). We would also like to thank Miss Jennifer Gates for the editing and proofreading of the manuscript.

Objective: Although the cerebello-thalamo-cortical network has often been suggested to be of importance in the pathogenesis of essential tremor (ET), the origins of tremorgenic activity in this disease are not fully understood. We used a combination of cortical thickness imaging and neurophysiological studies to analyze whether the severity of tremor was associated with anatomical changes in the brain in ET patients. Methods: Magnetic resonance imaging (MRI) and a neurophysiological assessment were performed in 13 nondemented ET patients. High field structural brain MRI images acquired in a 3T scanner and analyses of cortical thickness and surface were carried out. Cortical reconstruction and volumetric segmentation was performed with the FreeSurfer image analysis software. We used high-density surface electromyography (hdEMG) and inertial measurement units (IMUs) to quantify the tremor severity in upper extrimities of patients. In particular, advanced computer tool was used to reliably identify discharge patterns of individual motor units from surface hdEMG and quantify motor unit synchronization. Results: We found significant association between increased motor unit synchronization (i.e., more severe tremor) and cortical changes (i.e., atrophy) in widespread cerebral cortical areas, including the left medial orbitofrontal cortex, left isthmus of the cingulate gyrus, right paracentral lobule, right lingual gyrus, as well as reduced left supramarginal gyrus (inferior parietal cortex), right isthmus of the cingulate gyrus, left thalamus, and left amygdala volumes. Interpretation: Given that most of these brain areas are involved in controlling movement sequencing, ET tremor could be the result of an involuntary activation of a program of motor behavior used in the genesis of voluntary repetitive movements., This work was funded by FEDER grant ; National Institutes of Health grant ; NINDS grants R01 NS39422;, R01 NS094607;, R01 NS085136;, R01 NS073872;, and R01 NS088257; European Commission grant ICT‐2011‐287739; Ministry of Economy and Competitiveness grant RTC‐2015‐3967‐1; Spanish Health Research Agency grants FIS PI12/01602; and FIS PI16/00451; Spanish Ministry of Economy and Competitiveness grants DPI‐2015‐68664‐C4‐1‐R; and DPI2015‐72638‐EXP; Claire O'Neil Essential Tremor Research grant ; Slovenian Research Agency grant J2‐7357.