Insight into the Relationship Between Motor and Cognitive Symptoms in Essential Tremor.

Essential tremor (ET) is a heterogeneous disorder characterized by bilateral upper limbs action tremor and, possibly, neurological signs of uncertain significance, including voluntary movement abnormalities and cognitive disturbances, i.e., the so-called 'soft' signs configuring the ET-plus definition. While motor and cognitive disturbances often coexist in ET, their interrelationship remains largely unexplored. Here we aim to further investigate the relationship between motor symptoms, objectively assessed through kinematic analysis, and cognitive dysfunctions in ET. Seventy ET patients underwent clinical examination, as well as kinematic recordings of tremor and finger tapping and a thorough cognitive assessment. We then tested clinic-demographic and kinematic differences between patients with and without cognitive abnormalities, i.e., with mild cognitive impairment (MCI). Correlation analysis served to explore potential associations between kinematic and cognitive data. Forty-three ET patients (61.42%) had MCI. ET-MCI patients exhibited reduced movement velocity during finger tapping compared to those with normal cognition (p < 0.001). Lower movement velocity during finger tapping was associated with poorer cognitive performance. Namely, we observed a correlation between movement velocity and performance on the Babcock Story Immediate and Delayed Recall Test (r = 0.52 and r = 0.45, both p < 0.001), as well as the interference memory task at 10 and 30 s (r = 0.3, p = 0.008 and r = 0.2, p = 0.03). In this study, we have provided data for a better pathophysiological interpretation of motor and cognitive signs in ET, including the role played by the cerebellum or extra-cerebellar areas, which possibly underpin both signs.

Clinical and kinematic characterization of parkinsonian soft signs in essential tremor.

BACKGROUND: Subtle parkinsonian signs, i.e., rest tremor and bradykinesia, are considered soft signs for defining essential tremor (ET) plus. OBJECTIVES: Our study aimed to further characterize subtle parkinsonian signs in a relatively large sample of ET patients from a clinical and neurophysiological perspective. METHODS: We employed clinical scales and kinematic techniques to assess a sample of 82 ET patients. Eighty healthy controls matched for gender and age were also included. The primary focus of our study was to conduct a comparative analysis of ET patients (without any soft signs) and ET-plus patients with rest tremor and/or bradykinesia. Additionally, we investigated the asymmetry and side concordance of these soft signs. RESULTS: In ET-plus patients with parkinsonian soft signs (56.10% of the sample), rest tremor was clinically observed in 41.30% of cases, bradykinesia in 30.43%, and rest tremor plus bradykinesia in 28.26%. Patients with rest tremor had more severe and widespread action tremor than other patients. Furthermore, we observed a positive correlation between the amplitude of action and rest tremor. Most ET-plus patients had an asymmetry of rest tremor and bradykinesia. There was no side concordance between these soft signs, as confirmed through both clinical examination and kinematic evaluation. CONCLUSIONS: Rest tremor and bradykinesia are frequently observed in ET and are often asymmetric but not concordant. Our findings provide a better insight into the phenomenology of ET and suggest that the parkinsonian soft signs (rest tremor and bradykinesia) in ET-plus may originate from distinct pathophysiological mechanisms.

Intra and inter-rater remote assessment of bradykinesia in Parkinson's disease / Evaluación remota de la bradicinesia en la enfermedad de Parkinson mediante análisis intra e inter evaluadores

Introduction: Reliable assessment of individuals with Parkinson's disease (PD) is essential for providing adequate treatment. Clinical assessment is a complex and time-consuming task, especially for bradykinesia, since its evaluation can be influenced by the degree of experience of the examiner, patient collaboration and individual bias. Improvement of the clinical evaluation can be obtained by considering assessments from several professionals. However, this is only true when inter and intra-rater agreement are high. Recently, the Movement Disorder Society highlighted, during the COVID-19 pandemic, the need to develop and validate technologies for remote assessment of the motor status of people with PD. Thus, this study introduces an objective strategy for the remote evaluation of bradykinesia using multi-specialist analysis. Methods: Twelve volunteers with PD participated and these were asked to execute finger tapping, hand opening/closing and pronation/supination movements. Each task was recorded and rated by fourteen PD health experts for each patient. The scores were assessed on an individual basis. Intra and inter-rater agreement and correlation were estimated. Results: The results showed that agreements and correlations between experienced examiners were high with low variability. In addition, group analysis was noted as possessing the potential to solve individual inconsistency bias. Conclusion: Furthermore, this study demonstrated the need for a group with prior training and experience, along with indicating the importance for the development of a clinical protocol that can use telemedicine for the evaluation of individuals with PD, as well as the inclusion of a specialized mediating group. In Addition, this research helps to the development of a valid remote assessment of bradykinesia.(AU)

Introducción: La evaluación confiable de las personas con la enfermedad de Parkinson (EP) es esencial para lograr con un tratamiento adecuado. La evaluación clínica es una tarea compleja y que requiere mucho tiempo, especialmente para la bradicinesia, ya que su evaluación puede verse influenciada por el grado de experiencia del examinador, la colaboración del paciente y el sesgo individual. La mejora de la evaluación clínica se puede obtener considerando las evaluaciones de varios profesionales. Sin embargo, esto solo es más preciso cuando el convenio intra e inter evaluadores es alto. Recientemente, la Sociedad de Trastornos del Movimiento destacó, durante la pandemia COVID-19, la necesidad de desarrollar y validar tecnologías para la evaluación remota del estado motor de las personas con EP. Por lo tanto, este estudio presenta una estrategia objetiva para la evaluación remota de la bradicinesia mediante un análisis multi evaluadores. Métodos: Participaron 12 voluntarios con EP y se les pidió que ejecutaran movimientos de golpeteo de dedos de las manos, movimientos con las manos y pronación-supinación de las manos. Cada ejecución del movimiento fue registrado y calificado por 14 expertos en salud. Las puntuaciones se evaluaron de forma individual. Se estimó el convenio y la correlación intra e inter evaluadores. Resultados: Los resultados mostraron que los convenios y las correlaciones inter evaluadores experimentados son altos con baja variabilidad. Además, se observó que el análisis de grupo posee el potencial de resolver el sesgo de inconsistencia individual. Conclusiones: De esta forma, este estudio demostró la necesidad de un grupo con formación y experiencia previa, señalando la importancia para el desarrollo de un protocolo clínico que utiliza la telemedicina para la evaluación de personas con EP y como la inclusión de un grupo mediador especializado. En realidad, esta investigación propone una evaluación remota eficaz de la bradicinesia.(AU)

Intra and inter-rater remote assessment of bradykinesia in Parkinson's disease.

INTRODUCTION: Reliable assessment of individuals with Parkinson's disease (PD) is essential for providing adequate treatment. Clinical assessment is a complex and time-consuming task, especially for bradykinesia, since its evaluation can be influenced by the degree of experience of the examiner, patient collaboration and individual bias. Improvement of the clinical evaluation can be obtained by considering assessments from several professionals. However, this is only true when inter and intra-rater agreement are high. Recently, the Movement Disorder Society highlighted, during the COVID-19 pandemic, the need to develop and validate technologies for remote assessment of the motor status of people with PD. Thus, this study introduces an objective strategy for the remote evaluation of bradykinesia using multi-specialist analysis. METHODS: Twelve volunteers with PD participated and these were asked to execute finger tapping, hand opening/closing and pronation/supination movements. Each task was recorded and rated by fourteen PD health experts for each patient. The scores were assessed on an individual basis. Intra and inter-rater agreement and correlation were estimated. RESULTS: The results showed that agreements and correlations between experienced examiners were high with low variability. In addition, group analysis was noted as possessing the potential to solve individual inconsistency bias. CONCLUSION: Furthermore, this study demonstrated the need for a group with prior training and experience, along with indicating the importance for the development of a clinical protocol that can use telemedicine for the evaluation of individuals with PD, as well as the inclusion of a specialized mediating group. In Addition, this research helps to the development of a valid remote assessment of bradykinesia.

Correlation Between Depression and Quality of Life Among Patients With Parkinson's Disease: An Analytical Cross-Sectional Study.

Introduction Parkinson's disease (PD) is a progressive complex degenerative disorder characterised by several motor and non-motor symptoms that result in disability and deterioration of the patient's quality of life (QOL). Depression is the most common non-motor symptom that may severely alter the QOL. The objective of this study was to examine the correlation between depression and QOL among patients with PD who received treatment from a movement disorder clinic of a tertiary care teaching hospital in South India. Methods This was an analytical cross-sectional study conducted among 220 PD patients who received treatment from a movement disorder clinic of a tertiary care teaching hospital in South India. The participants aged between 40 and 80 years, who can comprehend Malayalam or English and were clinically diagnosed with PD according to United Kingdom PD Society Brain Bank criteria were included in the study. Depression was assessed using the Hospital Anxiety and Depression Scale, motor function using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, and the quality of life was assessed using the Parkinson's Disease Questionnaire 39. Results The results of this study showed that there was a significant positive correlation between depression and QOL (r=0.699, p<0.01) among patients with PD who received treatment from a tertiary care teaching hospital. The correlation with domains of QOL also identified that depression was significantly correlated with all domains of QOL and more to the emotional domain of QOL (r=0.799, p<0.01). Conclusion Depression is the most common neuropsychiatric condition in PD and the most important determinant of QOL. Depression may occur at any stage of PD and can significantly impact the QOL of patients and their caregivers. Hence it should be recognized early and managed by pharmacological and nonpharmacological measures to improve the QOL.

Impaired performance of rapid grip in people with Parkinson's disease and motor segmentation.

Bradykinesia, or slow movement, is a defining symptom of Parkinson's disease (PD), but the underlying neuromechanical deficits that lead to this slowness remain unclear. People with PD often have impaired rates of motor output accompanied by disruptions in neuromuscular excitation, causing abnormal, segmented, force-time curves. Previous investigations using single-joint models indicate that agonist electromyogram (EMG) silent periods cause motor segmentation. It is unknown whether motor segmentation is evident in more anatomically complex and ecologically important tasks, such as handgrip tasks. Aim 1 was to determine how handgrip rates of force change compare between people with PD and healthy young and older adults. Aim 2 was to determine whether motor segmentation is present in handgrip force and EMG measures in people with PD. Subjects performed rapid isometric handgrip pulses to 20-60% of their maximal voluntary contraction force while EMG was collected from the grip flexors and extensors. Dependent variables included the time to 90% peak force, the peak rate of force development, the duration above 90% of peak force, the number of segments in the force-time curve, the number of EMG bursts, time to relaxation from 90% of peak force, and the peak rate of force relaxation. People with PD had longer durations and lower rates of force change than young and older adults. Six of 22 people with PD had motor segmentation. People with PD had more EMG bursts compared to healthy adults and the number of EMG bursts covaried with the number of segments. Thus, control of rapid movement in Parkinson's disease can be studied using isometric handgrip. People with PD have impaired rate control compared to healthy adults and motor segmentation can be studied in handgrip.

Functional interaction of abnormal beta and gamma oscillations on bradykinesia in parkinsonian rats.

Bradykinesia, a debilitating symptom characterized by impaired movement initiation and reduced speed in Parkinson's disease (PD), is associated with abnormal oscillatory activity in the motor cortex-basal ganglia circuit. We investigated the interplay between abnormal beta and gamma oscillations in relation to bradykinesia in parkinsonian rats. Our findings showed reduced movement activities in parkinsonian rats, accompanied by enhanced high beta oscillations in the motor cortex, which are closely associated with movement transitional difficulties. Additionally, gamma oscillations correlated with movement velocity in control rats but not in parkinsonian rats. We observed selective coupling between high beta oscillation phase and gamma oscillation amplitude in PD, as well as cortical high beta-broadband gamma phase-amplitude coupling (PAC) negatively influencing locomotor activities in control and PD rats. These findings suggest a collaborative role of cortical beta and gamma oscillations in facilitating movement execution, with beta oscillations being linked to movement initiation and gamma oscillations associated with movement speed. Importantly, the aberrant alterations of these oscillations are closely related to the development of bradykinesia. Furthermore, PAC hold promise as a biomarker for comprehensive assessment of movement performance in PD.

Novel characteristics of the temporal transition to maximum tongue pressure in Parkinson's disease: A pilot study.

Introduction: The reason why maximum tongue pressure (MTP) decreases in patients with Parkinson's disease (PD) remains unclear. Repeated measurements of isometric force and MTP may be useful for analyzing muscle wasting and force generation. The purpose of this pilot study was to evaluate the clinical characteristics and temporal transition of MTP in PD and normal control (NC) groups. Methods: There were 18 participants in this study: 10 with PD and 8 NCs. The MTP was measured 20 times at regular intervals. The area under the curve of MTP temporal transitions, time to reach MTP, and total transition time of the tongue pressure (time to return to baseline) were compared between the groups. Results: MTP decreased from baseline in PD subjects. Unlike NCs, PD subjects showed diverse and inconsistent temporal transitions. The decrease in MTP and delays in time to reach MTP and time to return to baseline were significantly greater in PD subjects (p < 0.05), while there was no group difference in area under the curve values. According to repeated-measures ANOVA, MTP was not different over time between PD subjects and NCs. Conclusion: In this study, muscle fatigue did not affect the decrease in MTP seen in PD subjects, or the diversity and inconsistency of the temporal transition in MTP in that group. These findings indicate that the motor control needed for the repeated, identical movements associated with MTP generation may be impaired in PD patients.

Oral-diadochokinesis between Parkinson's disease and neurotypical elderly among Malaysian-Malay speakers.

BACKGROUND: Parkinson's disease (PD) has an impact on speech production, manifesting in various ways including alterations in voice quality, challenges in articulating sounds and a decrease in speech rate. Numerous investigations have been conducted to ascertain the oral-diadochokinesis (O-DDK) rate in individuals with PD. However, the existing literature lacks exploration of such O-DDK rates in Malaysia and does not provide consistent evidence regarding the advantage of real-word repetition. AIMS: To explore the effect of gender, stimuli type and PD status and their interactions on the O-DDK rates among Malaysian-Malay speakers. METHODS & PROCEDURES: O-DDK performance of 62 participants (29 individuals with PD and 33 healthy elderly) using a non-word ('pataka'), a Malay real-word ('patahkan') and an English real-word ('buttercake') was audio recorded. The number of syllables produced in 8 s was counted. A hierarchical linear modelling was performed to investigate the effects of stimuli type (non-word, Malay real-word, English real-word), PD status (yes, no), gender (male, female) and their interactions on the O-DDK rate. The model accounted for participants' age as well as the nesting of repeated measurements within participants, thereby providing unbiased estimates of the effects. OUTCOMES & RESULTS: The stimuli effect was significant (p < 0.0001). Malay real-word showed the lowest O-DDK rate (5.03 ± 0.11 syllables/s), followed by English real-word (5.25 ± 0.11 syllables/s) and non-word (5.42 ± 0.11 syllables/s). Individuals with PD showed a significantly lower O-DDK rate compared to healthy elderly (4.73 ± 0.15 syllables/s vs. 5.74 ± 0.14 syllables/s, adjusted p < 0.001). A subsequent analysis indicated that the O-DDK rate declined in a quadratic pattern. However, neither gender nor age effects were observed. Additionally, no significant two-way interactions were found between stimuli type, PD status and gender (all p > 0.05). Therefore, the choice of stimuli type has no or only limited effect considering the use of O-DDK tests in clinical practice for diagnostic purposes. CONCLUSIONS & IMPLICATIONS: The observed slowness in O-DDK among individuals with PD can be attributed to the impact of the movement disorder, specifically bradykinesia, on the physiological aspects of speech production. Speech-language pathologists can gain insights into the impact of PD on speech production and tailor appropriate intervention strategies to address the specific needs of individuals with PD according to disease stages. WHAT THIS PAPER ADDS: What is already known on this subject The observed slowness in O-DDK rates among individuals with PD may stem from the movement disorder's effects on the physiological aspects of speech production, particularly bradykinesia. However, there is a lack of consistent evidence regarding the influence of real-word repetition and how O-DDK rates vary across different PD stages. What this study adds to existing knowledge The O-DDK rates decline in a quadratic pattern as the PD progresses. The research provides insights into the advantage of real-word repetition in assessing O-DDK rates, with Malay real-word showing the lowest O-DDK rate, followed by English real-word and non-word. What are the potential or actual clinical implications of this work? Speech-language pathologists can better understand the evolving nature of speech motor impairments as PD progresses. This insight enables them to design targeted intervention strategies that are sensitive to the specific needs and challenges associated with each PD stage. This finding can guide clinicians in selecting appropriate assessment tools for evaluating speech motor function in PD patients.

Time-resolved quantification of fine hand movements as a proxy for evaluating bradykinesia-induced motor dysfunction.

Bradykinesia is a behavioral manifestation that contributes to functional dependencies in later life. However, the current state of bradykinesia indexing primarily relies on subjective, time-averaged categorizations of motor deficits, which often yield poor reliability. Herein, we used time-resolved analyses of accelerometer recordings during standardized movements, data-driven factor analyses, and linear mixed effects models (LMEs) to quantitatively characterize general, task- and therapy-specific indices of motor impairment in people with Parkinson's disease (PwP) currently undergoing treatment for bradykinesia. Our results demonstrate that single-trial, accelerometer-based features of finger-tapping and rotational hand movements were significantly modulated by divergent therapeutic regimens. Further, these features corresponded well to current gold standards for symptom monitoring, with more precise predictive capacities of bradykinesia-specific declines achieved when considering kinematic features from diverse movement types together, rather than in isolation. Herein, we report data-driven, sample-specific kinematic profiles of diverse movement types along a continuous spectrum of motor impairment, which importantly, preserves the temporal scale for which biomechanical fluctuations in motor deficits evolve in humans. Therefore, this approach may prove useful for tracking bradykinesia-induced motor decline in aging populations the future.

The Motor Dysfunction Seen in Isolated REM Sleep Behavior Disorder.

BACKGROUND: Isolated Rapid Eye Movement (REM) sleep Behavior Disorder (iRBD) requires quantitative tools to detect incipient Parkinson's disease (PD). METHODS: A motor battery was designed and compared with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III) in people with iRBD and controls. This included two keyboard-based tests (BRadykinesia Akinesia INcoordination tap test and Distal Finger Tapping) and two dual tasking tests (walking and finger tapping). RESULTS: We included 33 iRBD patients and 29 controls. The iRBD group performed both keyboard-based tapping tests more slowly (P < 0.001, P = 0.020) and less rhythmically (P < 0.001, P = 0.006) than controls. Unlike controls, the iRBD group increased their walking duration (P < 0.001) and had a smaller amplitude (P = 0.001) and slower (P = 0.007) finger tapping with dual task. The combination of the most salient motor markers showed 90.3% sensitivity for 89.3% specificity (area under the ROC curve [AUC], 0.94), which was higher than the MDS-UPDRS-III (minus action tremor) (69.7% sensitivity, 72.4% specificity; AUC, 0.81) for detecting motor dysfunction. CONCLUSION: Speed, rhythm, and dual task motor deterioration might be accurate indicators of incipient PD in iRBD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Interhemispheric imbalance and bradykinesia features in Parkinson's disease.

In patients with Parkinson's disease, the connectivity between the two primary motor cortices may be altered. However, the correlation between asymmetries of abnormal interhemispheric connections and bradykinesia features has not been investigated. Furthermore, the potential effects of dopaminergic medications on this issue remain largely unclear. The aim of the present study is to investigate the interhemispheric connections in Parkinson's disease by transcranial magnetic stimulation and explore the potential relationship between interhemispheric inhibition and bradykinesia feature asymmetry in patients. Additionally, we examined the impact of dopaminergic therapy on neurophysiological and motor characteristics. Short- and long-latency interhemispheric inhibition was measured in 18 Parkinson's disease patients and 18 healthy controls, bilaterally. We also assessed the corticospinal and intracortical excitability of both primary motor cortices. We conducted an objective analysis of finger-tapping from both hands. Correlation analyses were performed to explore potential relationships among clinical, transcranial magnetic stimulation and kinematic data in patients. We found that short- and long-latency interhemispheric inhibition was reduced (less inhibition) from both hemispheres in patients than controls. Compared to controls, finger-tapping movements in patients were slower, more irregular, of smaller amplitudes and characterized by a progressive amplitude reduction during movement repetition (sequence effect). Among Parkinson's disease patients, the degree of short-latency interhemispheric inhibition imbalance towards the less affected primary motor cortex correlated with the global clinical motor scores, as well as with the sequence effect on the most affected hand. The greater the interhemispheric inhibition imbalance towards the less affected hemisphere (i.e. less inhibition from the less to the most affected primary motor cortex than that measured from the most to the less affected primary motor cortex), the more severe the bradykinesia in patients. In conclusion, the inhibitory connections between the two primary motor cortices in Parkinson's disease are reduced. The interhemispheric disinhibition of the primary motor cortex may have a role in the pathophysiology of specific bradykinesia features in patients, i.e. the sequence effect.

The sound of Parkinson's disease: A model of audible bradykinesia.

INTRODUCTION: Evaluation of bradykinesia is based on five motor tasks from the MDS-UPDRS. Visually scoring these motor tasks is subjective, resulting in significant interrater variability. Recent observations suggest that it may be easier to hear the characteristic features of bradykinesia, such as the decrement in sound intensity or force of repetitive movements. The objective is to evaluate whether audio signals derived during four MDS-UPDRS tasks can be used to detect and grade bradykinesia, using two machine learning models. METHODS: 54 patients with Parkinson's disease and 28 healthy controls were filmed while executing the bradykinesia motor tasks. Several features were extracted from the audio signal, including number of taps, speed, sound intensity, decrement and freezes. For each motor task, two supervised machine learning models were trained, Logistic Regression (LR) and Support Vector Machine (SVM). RESULTS: Both classifiers were able to separate patients from controls reasonably well for the leg agility task, area under the receiver operating characteristic curve (AUC): 0.92 (95%CI: 0.78-0.99) for LR and 0.93 (0.81-1.00) for SVM. Also, models were able to differentiate less severe bradykinesia from severe bradykinesia, particularly for the pronation-supination motor task, with AUC: 0.90 (0.62-1.00) for LR and 0.82 (0.45-0.97) for SVM. CONCLUSION: This audio-based approach discriminates PD from healthy controls with moderate-high accuracy and separated individuals with less severe bradykinesia from those with severe bradykinesia. Sound analysis may contribute to the identification and monitoring of bradykinesia.

The Story behind the Mask: A Narrative Review on Hypomimia in Parkinson's Disease.

Facial movements are crucial for social and emotional interaction and well-being. Reduced facial expressions (i.e., hypomimia) is a common feature in patients with Parkinson's disease (PD) and previous studies linked this manifestation to both motor symptoms of the disease and altered emotion recognition and processing. Nevertheless, research on facial motor impairment in PD has been rather scarce and only a limited number of clinical evaluation tools are available, often suffering from poor validation processes and high inter- and intra-rater variability. In recent years, the availability of technology-enhanced quantification methods of facial movements, such as automated video analysis and machine learning application, led to increasing interest in studying hypomimia in PD. In this narrative review, we summarize the current knowledge on pathophysiological hypotheses at the basis of hypomimia in PD, with particular focus on the association between reduced facial expressions and emotional processing and analyze the current evaluation tools and management strategies for this symptom, as well as future research perspectives.

Motivational Vigor in Parkinson's Disease Requires the Short and Long Duration Response to Levodopa.

BACKGROUND: Impaired movement vigor (bradykinesia) is a cardinal feature of Parkinson's disease (PD) and hypothesized to result from abnormal motivational processes-impaired motivation-vigor coupling. Dopamine replacement therapy (DRT) improves bradykinesia, but the response to DRT is multifaceted, comprising a short-duration response (SDR) and a long-duration response (LDR) only manifesting with chronic treatment. Prior experiments assessing motivation-vigor coupling in PD used chronically treated subjects, obscuring the roles of the SDR and LDR. METHODS: To disambiguate the SDR and LDR, 11 de novo PD subjects (6 male [M]:5 female [F]; mean age, 67) were studied before treatment, after an acute levodopa (l-dopa) dose, and in both the practical "off" (LDR) and "on" (LDR + SDR) states after chronic stable treatment. At each visit, subjects were characterized with a standard battery including the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and an incentivized joystick task to assess motor performance in response to varying rewards. RESULTS: l-Dopa induced a robust SDR and LDR, with further improvement in the combined SDR + LDR state. At baseline, after acute treatment (SDR), and after LDR induction, subjects did not exhibit the normal increase in movement speed with increasing reward. Only in the combined SDR + LDR state was there restoration of motivation-vigor coupling. CONCLUSIONS: Although consistent with prior results in chronically treated PD subjects, the significant improvement in motor performance observed with the SDR and LDR suggests that bradykinesia is not solely secondary to deficient modulation of motivational processes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objective assessment of the effects of opicapone in Parkinson's disease through kinematic analysis.

BACKGROUND: Opicapone (OPC) is a third-generation, selective peripheral COMT inhibitor that improves peripheral L-DOPA bioavailability and reduces OFF time and end-of-dose motor fluctuations in Parkinson's disease (PD) patients. OBJECTIVES: In this study, we objectively assessed the effects of adding OPC to L-DOPA on bradykinesia in PD through kinematic analysis of finger movements. METHODS: We enrolled 20 treated patients with PD and motor fluctuations. Patients underwent two experimental sessions (L-DOPA, L-DOPA + OPC), separated by at least 1 week. In each session, patients were clinically evaluated and underwent kinematic movement analysis of repetitive finger movements at four time points: (i) before their usual morning dose of L-DOPA (T0), (ii) 30 min (T1), (iii) 1 h and 30 min (T2), and (iv) 3 h and 30 min after the L-DOPA intake (T3). RESULTS: Movement velocity and amplitude of finger movements were higher in PD patients during the session with OPC compared to the session without OPC at all the time points tested. Importantly, the variability of finger movement velocity and amplitude across T0-T3 was significantly lower in the L-DOPA + OPC than L-DOPA session. CONCLUSIONS: This study is the first objective assessment of the effects of adding OPC to L-DOPA on bradykinesia in patients with PD and motor fluctuations. OPC, in addition to the standard dopaminergic therapy, leads to significant improvements in bradykinesia during clinically relevant periods associated with peripheral L-DOPA dynamics, i.e., the OFF state in the morning, delayed-ON, and wearing-OFF periods.

Ucp4 Knockdown of Cerebellar Purkinje Cells Induces Bradykinesia.

Although uncoupling protein 4 (UCP4) is the most abundant protein reported in the brain, the biological function of UCP4 in cerebellum and pathological outcome of UCP4 deficiency in cerebellum remain obscure. To evaluate the role of Ucp4 in the cerebellar Purkinje cells (PCs), we generated the conditional knockdown of Ucp4 in PCs (Pcp2cre;Ucp4fl/fl mice) by breeding Ucp4fl/fl mice with Pcp2cre mice. Series results by Western blot, immunofluorescent staining, and triple RNAscope in situ hybridization confirmed the specific ablation of Ucp4 in PCs in Pcp2cre;Ucp4fl/fl mice, but did not affect the expression of Ucp2, the analog of Ucp4. Combined behavioral tests showed that Pcp2cre;Ucp4fl/fl mice displayed a characteristic bradykinesia in the spontaneous movements. The electromyogram recordings detection excluded the possibility of hypotonia in Pcp2cre;Ucp4fl/fl mice. And the electrical patch clamp recordings showed the altered properties of PCs in Pcp2cre;Ucp4fl/fl mice. Moreover, transmission electron microscope (TEM) results showed the increased mitochondrial circularity in PCs; ROS probe imaging showed the increased ROS generation in molecular layer; and finally, microplate reader assay showed the significant changes of mitochondrial functions, including ROS, ATP, and MMP in the isolated cerebellum tissue. The results suggested that the specific knockdown of mitochondrial protein Ucp4 could damage PCs possibly by attacking their mitochondrial function. The present study is the first to report a close relationship between UCP4 deletion with PCs impairment, and suggests the importance of UCP4 in the substantial support of mitochondrial function homeostasis in bradykinesia. UCP4 might be a therapeutic target for the cerebellar-related movement disorder.

Monipar: movement data collection tool to monitor motor symptoms in Parkinson's disease using smartwatches and smartphones.

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder commonly characterized by motor impairments. The development of mobile health (m-health) technologies, such as wearable and smart devices, presents an opportunity for the implementation of clinical tools that can support tasks such as early diagnosis and objective quantification of symptoms. Objective: This study evaluates a framework to monitor motor symptoms of PD patients based on the performance of standardized exercises such as those performed during clinic evaluation. To implement this framework, an m-health tool named Monipar was developed that uses off-the-shelf smart devices. Methods: An experimental protocol was conducted with the participation of 21 early-stage PD patients and 7 healthy controls who used Monipar installed in off-the-shelf smartwatches and smartphones. Movement data collected using the built-in acceleration sensors were used to extract relevant digital indicators (features). These indicators were then compared with clinical evaluations performed using the MDS-UPDRS scale. Results: The results showed moderate to strong (significant) correlations between the clinical evaluations (MDS-UPDRS scale) and features extracted from the movement data used to assess resting tremor (i.e., the standard deviation of the time series: r = 0.772, p < 0.001) and data from the pronation and supination movements (i.e., power in the band of 1-4 Hz: r = -0.662, p < 0.001). Conclusion: These results suggest that the proposed framework could be used as a complementary tool for the evaluation of motor symptoms in early-stage PD patients, providing a feasible and cost-effective solution for remote and ambulatory monitoring of specific motor symptoms such as resting tremor or bradykinesia.

Anatomical substrates and connectivity for bradykinesia motor features in Parkinson's disease after subthalamic nucleus deep brain stimulation.

Parkinsonian bradykinesia is rated using a composite scale incorporating the slowed frequency of repetitive movements, decrement amplitude and arrhythmicity. Differential localization of these movement components within the basal ganglia will drive the development of more personalized network-targeted symptomatic therapies. In this study, using an optical motion sensor, we evaluated the amplitude and frequency of hand movements during a grasping task with subthalamic nucleus deep brain stimulation 'on' or 'off' in 15 patients with Parkinson's disease. The severity of bradykinesia was assessed blindly using the Unified Parkinson's Disease Rating Part III scale. The volumes of activated tissue of each subject were estimated where changes in amplitude and frequency were mapped to identify distinct anatomical substrates of each component in the subthalamic nucleus. The volumes of activated tissue were used to seed a normative functional connectome to generate connectivity maps associated with amplitude and frequency changes. Deep brain stimulation-induced change in amplitude was negatively correlated with a change in Unified Parkinson's Disease Rating Part III scale for right (r = -0.65, P < 0.05) and left hand grasping scores (r = -0.63, P < 0.05). The change in frequency was negatively correlated with amplitude for both right (r = -0.63, P < 0.05) and left hands (r = -0.57, P < 0.05). The amplitude and frequency changes were represented as a spatial gradient with overlapping and non-overlapping regions spanning the anteromedial-posterolateral axis of the subthalamic nucleus. Whole-brain correlation maps between functional connectivity and motor changes were also inverted between amplitude and frequency changes. Deep brain stimulation-associated changes in frequency and amplitude were topographically and distinctly represented both locally in the subthalamic nucleus and in whole-brain functional connectivity.

Depression in Patients With Parkinson's Disease: A Hospital-Based Cross-Sectional Study.

INTRODUCTION: Depression, a common non-motor symptom in Parkinson's disease (PD), is often underdiagnosed and can significantly impact the quality of life (QOL) and treatment outcomes. Specific disease-related factors and non-specific factors may contribute to depression, and these factors should be identified early to plan the appropriate interventions that promote positive mood. The study aimed to assess the prevalence of depression in PD patients and to find out the factors associated with depression among patients with PD attending the neurology OPD of a tertiary care teaching hospital in Trivandrum. METHODS: A cross-sectional study was conducted at the neurology OPD of Government Medical College Hospital, Trivandrum, from December 2021 to February 2023. We included patients with PD diagnosed according to the United Kingdom PD Society Brain Bank criteria. We collected data from 220 patients with PD by interview technique. Hospital Anxiety and Depression Scale (HADS) was used to assess depression and anxiety in this study. Staging and the severity of the motor symptoms were assessed using the Hoehn and Yahr scale and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS UPDRS Part III), respectively. RESULTS: Among 220 patients with PD, 31.8% (95% CI: 4.36-5.40) had depression. The non-specific variables, such as education, living arrangements, and gender, and disease-specific variables, such as the severity of motor symptoms (MDS UPDRS Part III score) and the Hoehn and Yahr staging of PD, had a statistically significant association with depression. Logistic regression analysis showed that the severity of motor symptoms (OR=2.69, p=0.004)) and female gender (OR=1.830, p= 0.05) were the independent factors associated with depression. CONCLUSION: Depression is a common non-motor symptom of PD that is often underdiagnosed and undertreated and can significantly impact the QOL of patients and their caregivers. Hence, it should be identified early and managed by pharmacological and non-pharmacological strategies.