Non-motor Domains Research Articles

HIV Dementia: A Bibliometric Analysis and Brief Review of the Top 100 Cited Articles.

Dementia is a syndrome of cognitive impairment that affects an individual’s ability to live independently. The number of people living with dementia worldwide in 2015 was estimated at 47.47 million. The American Academy of Neurology (AAN) criteria for human immunodeficiency virus (HIV)-associated dementia (HAD) require an acquired abnormality in at least two cognitive (non-motor) domains and either an abnormality in motor function or specified neuropsychiatric/psychosocial domains. HIV is the most common cause of dementia below 60 years of age.Citation frequencies are commonly used to assess the scholarly impact of any scientific publication in bibliometric analyses. It helps depict areas of higher interest in terms of research frequency and trends of citations in the published literature and identify under-explored domains of any field, providing useful insight and guidance for future research avenues. We used the database “Web of Science” (WOS) to search for the top 100 cited articles on HIV-associated dementia. The keywords “HIV dementia” and “HIV-associated neurocognitive disorders” (HAND) were used. The list was generated by two authors after excluding articles not pertaining to HIV dementia. The articles were then assigned to authors to extract data to make tables and graphical representations. Finally, the manuscript was organized and written describing the findings of the bibliometric study.These 100 most cited articles on HIV dementia were published between years 1986 and 2016. The highest number of the articles was from 1999 (n=9). The year 1993-2007 contributed consistently two publications to the list. The articles are from 42 journals, and among them, the Annals of Neurology (n=16) and the Journal of Neurology (n=15) published most of the articles. Justin C. McArthur with 25 publications contributed the highest number of papers to the list by any author. The USA collaborated in the highest number of publications (n=87). American institutes were leading the list with the most publications. The Johns Hopkins University collaborated on 37 papers. The most widely studied aspect of HIV dementia was pathogenesis. Incidence and prevalence, clinical features, and pre- and post-highly active antiretroviral therapy (HAART) era were also discussed in the articles.Beyond America, the research should be expanded to low-income countries and those affected more by HIV. Therefore, other countries and their institutes should participate more in HIV-associated dementia research. Anticipating the rising resistance to existing antiretrovirals, we should develop new therapeutic options. There is room for research in many aspects of HIV dementia care.

P 33 Changes in functional connectivity relate to modulation of cognitive control by subthalamic stimulation

Introduction Using cognitive control, humans can flexibly influence behavior based on set goals, which includes overriding impulses by inhibiting automatic responses in a conflicting environment. The basal ganglia have been hypothesized as an integral part in a cortico-subcortical network that modulates inhibitory control in both motor and non-motor domains. Subthalamic (STN) deep brain stimulation (DBS) in Parkinson‘s disease (PD) patients not only improves kinematic parameters of movement but also modulates cognitive control in the motor and non-motor domain, especially in situations of high conflict. Materials & Methods During DBS ON and OFF conditions, we conducted a visuomotor task in 14 PD patients who previously underwent resting-state functional MRI (rs-fMRI) acquisitions DBS ON and OFF. In the task, participants had to move a cursor with a pen on a digital tablet either towards (automatic condition) or in the opposite direction (controlled condition) of a target. Behaviorally, the first main outcome parameter was reaction time, and specifically, the difference in reaction time between automatic and controlled condition that reflects the additional time associated with engagement of cognitive control. Furthermore, average movement velocity ON vs. OFF DBS in automatic and controlled trials was assessed. Analysis of the imaging data focused on STN DBS induced modulation of rs-fMRI connectivity as a function of changes in behavior ON vs. OFF DBS and was estimated using link-wise network-based statistics within an a-priori defined network parcellation with 7 bihemispheric regions of interest (STN, internal/external pallidum (GPi and GPe), striatum, motor thalamus (VAn, VAp, VLd/VLv nuclei combined), motor and premotor cortices, supplementary motor area (SMA) and pre-SMA). Results Behavioral results showed diminished reaction time adaptation under DBS, i.e., PD patients ON DBS slowed down significantly less in the controlled condition compared to the automatic condition than they did OFF DBS. Additionally, pen-to-target movement velocity was increased under DBS in both automatic and controlled condition. Resting-state imaging data analysis revealed that DBS-induced reaction time reduction was associated with attenuated functional connectivity between cortical motor areas, basal ganglia and thalamus. On the other hand, increased movement velocity ON DBS was associated with stronger pallido-thalamic connectivity. Conclusion These findings suggest that DBS-induced decoupling of a motor cortico-basal ganglia network underlies impaired inhibitory control in PD patients undergoing subthalamic DBS and highlight the concept of functional network modulation through DBS. Understanding the connectivity basis of nonmotor changes in PD patients treated with DBS has a high clinical relevance, since network modulation may be fine-tuned with advancing therapeutic developments such as adaptive stimulation.

P 38 Prediction of cognitive outcome of Parkinson's disease patients after subthalamic deep brain stimulation

Introduction: Parkinson's disease is a slowly progressive, neurodegenerative disease affecting both motor and non-motor domains. As the disease progresses, cognitive symptoms and dementia become the leading unmet therapeutic need. This is of particular relevance for therapeutic stratification of subthalamic deep brain stimulation which leads to a reliable control of dopaminergic response fluctuations. However, cognitive decline may hamper the therapeutic long-term success. The aim of this retrospective study was to determine preoperative variables that predict cognitive decline in in the long-term after deep brain stimulation. Method: We included 95 patients. MOCA was used to evaluate cognition preoperatively and postoperative in annual intervals. Further patient characteristics were included to the analysis including gender, age at DBS implantation, disease duration at the time of surgery, and motor impairment expressed as UPDRS III. We performed Kaplan-Meier analysis to evaluate the conversion of the preoperative cognitively competent patients (MoCA ≥ 26) to mild cognitive impairment (MoCA <26) or dementia (MoCA < 17). We used Cox-regression to assess the influence of various factors on the probability of occurrence of dementia and MCI in IPS patients. The log-rank test was conducted to compare the statistical survival time. Results: 64.2% of patients developed a MCI, and 12 patients (12.6%) developed dementia after implantation. the percentage of patients who developed MCI 5 years after implantation was estimated at around 56%, 10 years later was this around 72% and 15 years after the operation was estimated at around 90%. In 34 patients no MCI occurred during the course (censored the mean survival time without an MCI was estimated at 6.1 years. After 4.3 years, half of the patients were expected to develop MCI (median survival time). The predictor “age> 70” predicted occurrence of MCI with a hazard ratio of 2.4 ( P =0.0051). “Female gender” was associated with a risk to develop dementia with a hazard ratio of 2.87 (non-significant trend P =0.08). Conclusion: This retrospective analysis suggests that elderly patients are at risk to develop MCI in the 5 years STN-DBS. This may reflect the higher risk of i) disease-related brain pathology and ii) aging. The delayed time course when developing MCI argues more for this combined effect and less for a direct detrimental effect of neuromodulation therapy on cognition.

Cerebellar Contributions to Social Cognition in ASD: A Predictive Processing Framework.

Functional, structural, and cytoarchitectural differences in the cerebellum are consistently reported in Autism Spectrum Disorders (ASD). Despite this, the mechanisms governing cerebellar contributions to ASD, particularly within the sociocognitive domain, are not well understood. Recently, it has been suggested that several core features of ASD may be associated with challenges creating and using prior expectations or predictions to rapidly adapt to changing stimuli or situations, also known as adaptive prediction. Importantly, neuroimaging, clinical, and animal work find that the cerebellum supports adaptive prediction in both motor and non-motor domains. Perturbations to the cerebellum via injury or neuromodulation have been associated with impairments in predictive skills. Here, we review evidence for a cerebellar role in social cognition and adaptive prediction across individuals with and without ASD.

Non-motor effects of subthalamic nucleus stimulation in Parkinson patients.

The current white matter connectivity analyses of the subthalamic region have focused on the motor effects of deep brain stimulation. We investigate white matter connectivity associated with the stimulation-induced non-motor acute clinical effects in three domains: mood changes, dizziness, and sweating. We performed whole-brain probabilistic tractography seeded from the domain-specific stimulation volumes. The resultant connectivity maps were statistically compared across patients. The cortical voxels associated with each non-motor domain were compared with stimulation-induced motor improvements in a multivariate model. The resulting voxel maps were thresholded for false discovery (FDR q < 0.05) and clustered using a multimodal atlas. We also performed a group-level parcellation of stimulation volumes to identify the local pathways associated with each non-motor domain. The non-motor effects were rarely observed during stimulation titration: from 1100 acute clinical effects, mood change was observed in 14, dizziness in 23, and sweating in 20. Distinct cortical clusters were associated with each domain; notably, mood change was associated with voxels in the salience network and dizziness with voxels in the visual association cortex. The subthalamic parcellation yielded a mediolateral gradient, with the motor parcel being lateral and the non-motor parcels medial. We also observed an anteroposterior organization in the medial non-motor clusters with mood changes being anterior, followed posteriorly by dizziness, and sweating. We interpret these findings based on the literature and foresee these to be useful in guiding DBS programming.

The role of frailty in Parkinson's disease: a cross-sectional study.

Frailty is an age-related state of increased risk for health-related adverse outcomes that reflects multisystem physiological changes and likely influences the clinical expression and disease progression of neurodegenerative disorders. The aim of the present study was to assess the potential relationship between frailty, as assessed by a frailty index (FI), and motor symptom severity, motor subtypes, and non-motor domains in Parkinson's disease (PD). We consecutively enrolled 150 PD patients. We administered an FI specifically designed for PD that included 50 age-related multidimensional biological deficits. Patients underwent a clinical assessment that evaluated motor and non-motor manifestations of PD. Using the FI score, we classified PD patients as relatively fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). A linear regression model was designed to explore possible associations between frailty level and PD motor and non-motor manifestations. Frail patients showed greater motor symptom severity and motor complications than fitter patients. A trend towards a higher prevalence of the postural instability/gait disorder subtype was also observed in frail versus relatively fit and less fit patients. The global burden of non-motor symptoms was higher in frail patients. Increased frailty was associated with more severe motor and non-motor symptoms, as well as with more pronounced cognitive deficits. These associations remained significant even when "traditional" predictors of PD severity (age, disease duration, and levodopa equivalent daily dose) were considered. The present findings indicate that the FI is associated with both motor and non-motor features of PD.

Fostering Holistic Development with a Designed Multisport Intervention in Physical Education: A Class-Randomized Cross-Over Trial.

Physical education (PE) is acknowledged as a relevant context for holistic child and youth development promotion. However, interventional research mostly builds on individual theories focused on specific outcome domains. This study presents a multisport enriched PE intervention that capitalizes on the intersection of different theory-based approaches to motor, cognitive and socio-emotional skills development promotion. With a cross-over design, 181 fifth graders, coming from a past class-randomized trial of enriched or traditional PE in their 1st–3rd grade, were stratified (based on their previous PE experience) and class-randomized to multisport enriched PE or control group. They completed pre-post assessments in motor and sport skills, cool (inhibition, working memory) and hot (decision making) executive functions, prosocial (empathy, cooperation) and antisocial (quick-temperedness, disruptiveness) behaviors. Children in the enriched PE group showed advantages in motor and prosocial skills after the intervention, which were linked by a mediation path, and an interactive effect of past and actual PE experience on decision making but no differential effects on other variables. The results suggest that a PE intervention designed with an integrative theory base, although not allowing disentangling the contribution of individual components to its efficacy, may help pursue benefits in motor and non-motor domains relevant to whole-child development.

One more time about motor (and non-motor) synergies.

We revisit the concept of synergy based on the recently translated classical book by Nikolai Bernstein (On the construction of movements, Medgiz, Moscow 1947; Latash, Bernstein's Construction of Movements, Routledge, Abingdon 2020b) and progress in understanding the physics and neurophysiology of biological action. Two aspects of synergies are described: organizing elements into stable groups (modes) and ensuring dynamical stability of salient performance variables. The ability of the central nervous system to attenuate synergies in preparation for a quick action-anticipatory synergy adjustments-is emphasized. Recent studies have demonstrated synergies at the level of hypothetical control variables associated with spatial referent coordinates for effectors. Overall, the concept of synergies fits naturally the hierarchical scheme of control with referent coordinates with an important role played by back-coupling loops within the central nervous system and from peripheral sensory endings. Further, we review studies showing non-trivial changes in synergies with development, aging, fatigue, practice, and a variety of neurological disorders. Two aspects of impaired synergic control-impaired stability and impaired agility-are introduced. The recent generalization of the concept of synergies for non-motor domains, including perception, is discussed. We end the review with a list of unresolved and troubling issues.

Domain-Specific Outcomes for Stroke Clinical Trials: What the Modified Rankin Isn't Ranking.

Global outcome measures that are widely used in stroke clinical trials, such as the modified Rankin Scale (mRS), lack sufficient detail to detect changes within specific domains (e.g., sensory, motor, visual, linguistic, or cognitive function). Yet such data are vital for understanding stroke recovery and its mechanisms. Poststroke deficits in specific domains differ in their rate and degree of recovery and in their effects on overall independence and quality of life. For example, even in a patient with complete recovery of strength, persistent deficits in the nonmotor domains such as language and cognition may make a return to independent living impossible. In such cases, global measures based solely on the patient's degree of independence would overlook a complete recovery in the motor domain. Capturing these important aspects of recovery demands a domain-specific approach. If stroke outcomes trials are to incorporate finer-grained recovery metrics-which can require substantial time, effort, and expertise to implement-efficiency must be a priority. In this article, we discuss how commonly collected clinical data from the NIH Stroke Scale can guide the judicious selection of relevant recovery domains for more detailed testing. Our overarching goal is to make the implementation of domain-specific testing more feasible for large-scale clinical trials on stroke recovery.

Mud binds the kinesin-14 Ncd in Drosophila

Maintenance of proper mitotic spindle structure is necessary for error-free chromosome segregation and cell division. Spindle assembly is controlled by force-generating kinesin motors that contribute to its geometry and bipolarity, and balancing motor-dependent forces between opposing kinesins is critical to the integrity of this process. Non-claret dysjunctional (Ncd), a Drosophila kinesin-14 member, crosslinks and slides microtubule minus-ends to focus spindle poles and sustain bipolarity. However, mechanisms that regulate Ncd activity during mitosis are underappreciated. Here, we identify Mushroom body defect (Mud), the fly ortholog of human NuMA, as a direct Ncd binding partner. We demonstrate this interaction involves a short coiled-coil domain within Mud (MudCC) binding the N-terminal, non-motor microtubule-binding domain of Ncd (NcdnMBD). We further show that the C-terminal ATPase motor domain of Ncd (NcdCTm) directly interacts with NcdnMBD as well. Mud binding competes against this self-association and also increases NcdnMBD microtubule binding in vitro. Our results describe an interaction between two spindle-associated proteins and suggest a potentially new mode of minus-end motor protein regulation at mitotic spindle poles.

Functional Role of the Cerebellum in Parkinson Disease: A PET Study.

To test for cerebellar involvement in motor and nonmotor impairments in Parkinson disease (PD) and to determine patterns of metabolic correlations with supratentorial brain structures, we correlated clinical motor, cognitive, and psychiatric scales with cerebellar metabolism. We included 90 patients with PD. Motor, cognitive, and psychiatric domains were assessed, and resting-state 18FDG-PET metabolic imaging was performed. The motor, cognitive, and psychiatric scores were entered separately into a principal component analysis. We looked for correlations between these 3 principal components and cerebellar metabolism. Furthermore, we extracted the mean glucose metabolism value for each significant cerebellar cluster and looked for patterns of cerebrum-cerebellum metabolic correlations. Severity of impairment was correlated with increased metabolism in the anterior lobes and vermis (motor domain); the right crus I, crus II, and declive (cognitive domain); and the right crus I and crus II (psychiatric domain). No results survived multiple testing corrections regarding the psychiatric domain. Moreover, we found distributed and overlapping, but not identical, patterns of metabolic correlations for motor and cognitive domains. Specific supratentorial structures (cortical structures, basal ganglia, and thalamus) were strongly correlated with each of the cerebellar clusters. These results confirm the role of the cerebellum in nonmotor domains of PD, with differential but overlapping patterns of metabolic correlations suggesting the involvement of cerebello-thalamo-striatal-cortical loops.

Impulse Control Disorders in Parkinson's Disease: From Bench to Bedside.

Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by symptoms that impact both motor and non-motor domains. Outside of motor impairments, PD patients are at risk for impulse control disorders (ICDs), which include excessively disabling impulsive and compulsive behaviors. ICD symptoms in PD (PD + ICD) can be broadly conceptualized as a synergistic interaction between dopamine agonist therapy and the many molecular and circuit-level changes intrinsic to PD. Aside from discontinuing dopamine agonist treatment, there remains a lack of consensus on how to best address ICD symptoms in PD. In this review, we explore recent advances in the molecular and neuroanatomical mechanisms underlying ICD symptoms in PD by summarizing a rapidly accumulating body of clinical and preclinical studies, with a special focus on the utility of rodent models in gaining new insights into the neurochemical basis of PD + ICD. We also discuss the relevance of these findings to the broader problem of impulsive and compulsive behaviors that impact a range of neuropsychiatric syndromes.

Regional Cerebral Cortical Atrophy is Related to Urinary Tract Symptoms in Parkinson's Disease.

Lower urinary tract symptoms (LUTS) are the most common nonmotor symptoms usually occurring mid-stage of Parkinson's disease (PD); however, its underlying mechanisms are unknown. We aimed to assess whether corticometry or volumetry can identify a pattern of cerebral cortical changes in PD patients with LUTS. We recruited 85 idiopathic PD patients and performed corticometry and volumetry on various cortical regions using each patient's magnetic resonance imaging. To identify a correlation between the cortical thickness/volume and nonmotor symptoms scale domain 7 scores, which represent the severity of LUTS, we performed general linear model and region of interest analyses. Significant regional thinning of the left precuneus, left temporal pole, left precentral, right precuneus, and right pars opercularis was correlated with nonmotor symptoms scale domain 7 scores. We also found that cortical volumes of left precuneus and left frontal pole were inversely correlated with the severity of urinary symptoms. This study showed that the thicknesses and volumes of several cortical regions were significantly correlated with the severity of LUTS in PD patients. The findings of regional atrophy and thinning of specific cortical regions in this study provide additional evidence that multiple cortical regions, especially the precuneus cortex, not only may be involved in urinary dysfunctions of PD patients but also may help to elucidate the exact underlying mechanisms for LUTS in PD patients.

Physical Activity Improves Anxiety and Apathy in Early Parkinson's Disease: A Longitudinal Follow-Up Study.

Objective: In a prospective study, we investigated the association between physical activity and various motor, non-motor outcomes, and quality of life in early Parkinson's disease (PD) participants in the PD Longitudinal Singapore Study.Background: Prospective studies that examined the association between physical activity and motor and non-motor domains in early PD are lacking.Methods: 121 PD participants were followed-up prospectively to evaluate the association of physical activity with various symptom domains. The Physical Activity Scale for the Elderly (PASE) was used to measure physical activity annually. PD-related symptoms were categorized by motor, non-motor, and quality of life measures. Multivariate regression with gain score analysis was performed to understand the association of baseline PASE scores with the change of each variable at 1-year follow-up.Results: Higher baseline PASE scores (greater activity) were associated with a younger age, lower MDS-UPDRS motor scores, a smaller levodopa equivalent daily dose, better attention and memory scores, and better QoL. Activity scores in early PD declined on follow-up. Multivariate analysis revealed higher baseline physical activity to be associated with decreased anxiety and apathy scores at 1-year follow-up, after adjusting for demographic variables and medications.Conclusion: We demonstrated that higher baseline physical activity was associated with improved anxiety and apathy symptoms in early PD over a 1-year period.

A causal role for the cerebellum in semantic integration: a transcranial magnetic stimulation study

Mounting evidence suggests that the cerebellum, a structure previously linked to motor function, is also involved in a wide range of non-motor processes. It has been proposed that the cerebellum performs the same computational processes in both motor and non-motor domains. Within motor functions, the cerebellum is involved in the integration of signals from multiple systems. Here we hypothesized that cerebellum may be involved in integration within semantic memory as well. Specifically, understanding a noun-adjective combination (e.g. red apple) requires combining the meaning of the adjective (red) with the meaning of the noun (apple). In two experiments, participants were asked to judge whether noun-adjective word-pairs were semantically related (e.g., red apple) or not (e.g., lucky milk) while online transcranial magnetic stimulation (TMS) was administered over the right cerebellum or over a control site (vertex in Experiment 1 and visual cortex in Experiment 2). Cerebellar TMS caused a decrease in participants’ accuracy for related word-pairs while accuracy for unrelated stimuli was not affected. A third experiment using a control task where subjects compared pairs of random letters showed no effect of TMS. Taken together these results indicate that the right cerebellum is involved specifically in the processing of semantically related stimuli. These results are consistent with theories that proposed the existence of a unified cerebellar function within motor and non-motor domains, as well with recent perspectives about cerebellar involvement in semantic memory and predictive cognition.

Tremor in Vascular Cognitive Impairment Raises the Possibility of Mixed Pathology With Lewy Body Disease

ObjectivesTremor is common in patients with Lewy body disease (LBD) and not rare in normal individuals. Prevalence of tremor in patients with vascular cognitive impairment (VCI) and its association with other comorbidities are seldom studied. The aim of this study was to investigate the patient characteristics of VCI associated with tremor and to evaluate the possibility of mixed pathology with LBD in these patients.MethodsRetrospective analysis of a large population with VCI registered in the database of a regional healthcare system was performed. VCI patients were divided into tremor and non-tremor groups. The associated characteristics including demographics, clinical features in motor and non-motor domains, vascular risk factors, and neuroimaging features were compared between the tremor group and the non-tremor group.ResultsAmong 1337 patients with VCI, 292 (21.8%) had tremor, while 1045 (78.2%) did not have tremor. The tremor group had significantly higher prevalence of all motor and non-motor LBD clinical features than the non-tremor group. The tremor group also demonstrated more severe neuropsychiatric symptoms. Among patients with tremor, patients having tremor onset earlier than stroke onset showed significantly higher prevalence of rapid eye movement sleep behavior disorder. All comparisons were adjusted for age and severity of dementia.ConclusionTremor is a common comorbidity of VCI. VCI patients with tremor had a higher prevalence of motor and non-motor LBD features. These findings raised the possibility of VCI patients with tremor having high possibility of mixed pathology with LBD.

Study protocol of the DUtch PARkinson Cohort (DUPARC): a prospective, observational study of de novo Parkinson\u2019s disease patients for the identification and validation of biomarkers for Parkinson\u2019s disease subtypes, progression and pathophysiology

BackgroundParkinson’s Disease (PD) is a heterogeneous, progressive neurodegenerative disorder which is characterized by a variety of motor and non-motor symptoms. To date, no disease modifying treatment for PD exists. Here, the study protocol of the Dutch Parkinson Cohort (DUPARC) is described. DUPARC is a longitudinal cohort study aimed at deeply phenotyping de novo PD patients who are treatment-naïve at baseline, to discover and validate biomarkers for PD progression, subtypes and pathophysiology.Methods/designDUPARC is a prospective cohort study in which 150 de novo PD subjects will be recruited through a collaborative network of PD treating neurologists in the northern part of the Netherlands (Parkinson Platform Northern Netherlands, PPNN). Participants will receive follow-up assessments after 1 year and 3 years, with the intention of an extended follow-up with 3 year intervals. Subjects are extensively characterized to primarily assess objectives within three major domains of PD: cognition, gastrointestinal function and vision. This includes brain magnetic resonance imaging (MRI); brain cholinergic PET-imaging with fluoroethoxybenzovesamicol (FEOBV-PET); brain dopaminergic PET-imaging with fluorodopa (FDOPA-PET); detailed neuropsychological assessments, covering all cognitive domains; gut microbiome composition; intestinal wall permeability; optical coherence tomography (OCT); genotyping; motor and non-motor symptoms; overall clinical status and lifestyle factors, including a dietary assessment; storage of blood and feces for additional analyses of inflammation and metabolic parameters. Since the start of the inclusion, at the end of 2017, over 100 PD subjects with a confirmed dopaminergic deficit on FDOPA-PET have been included.DiscussionDUPARC is the first study to combine data within, but not limited to, the non-motor domains of cognition, gastrointestinal function and vision in PD subjects over time. As a de novo PD cohort, with treatment naïve subjects at baseline, DUPARC provides a unique opportunity for biomarker discovery and validation without the possible confounding influences of dopaminergic medication.Trial registrationNCT04180865; registered retrospectively, November 28th 2019.

Effect of home-based Tai Chi, Yoga or conventional balance exercise on functional balance and mobility among persons with idiopathic Parkinson's disease: An experimental study.

Background:Individuals with Parkinson’s disease (PD) invariably experience functional decline in a number of motor and non-motor domains affecting posture, balance and gait. Numerous clinical studies have examined effects of various types of exercise on motor and non-motor problems. But still much gap remains in our understanding of various therapies and their effect on delaying or slowing the dopamine neuron degeneration. Recently, Tai Chi and Yoga both have gained popularity as complementary therapies, since both have components for mind and body control.Objective:The aim of this study was to determine whether eight weeks of home-based Tai Chi or Yoga was more effective than regular balance exercises on functional balance and mobility.Methods:Twenty-seven individuals with Idiopathic PD (Modified Hoehn and Yahr stages 2.5–3) were randomly assigned to either Tai Chi, Yoga or Conventional exercise group. All the participants were evaluated for Functional Balance and Mobility using Berg Balance Scale, Timed 10 m Walk test and Timed Up and Go test before and after eight weeks of training.Results:The results were analyzed using two-way mixed ANOVA which showed that there was a significant main effect for time as F (1, 24) 74.18, , for overall balance in Berg Balance Scale. There was also significant main effect of time on mobility overall as F(1, 24) , , in Timed up and Go test and F(1, 24) , , for 10 m Walk test. There was a significant interaction effect for with F(2, 24) , , for balance. With respect to mobility, the values F(2, 24) , , in Timed Up and Go test and F(2, 24) , , in 10 m Walk test showed a significant interaction. But there was no significant main effect between the groups for both balance and mobility.Conclusion:The findings of this study suggest that Tai Chi as well as Yoga are well adhered and are attractive options for a home-based setting. As any form of physical activity is considered beneficial for individuals with PD either Tai Chi, Yoga or conventional balance exercises could be used as therapeutic intervention to optimize balance and mobility. Further studies are necessary to understand the mind–body benefits of Tai Chi and Yoga either as multicomponent physical activities or as individual therapies in various stages of PD.

The Clinical Non-Motor Connectome in Early Parkinson's Disease.

Background:Non-motor symptoms (NMS) of various anatomical origins are seen in early stage idiopathic Parkinson’s disease (IPD).Objective:To analyse when and how NMS are linked together at this stage of the disease.Methods:Prospective study recruiting 64 IPD patients with ≤3 years of disease duration and 71 age-matched healthy controls (HC). NMS were clustered in 7 non-motor domains (NMD): general cognition, executive function, visuospatial function, autonomic function, olfaction, mood, and sleep. Correlation coefficients ≥|0.3| were considered as significant. Bootstrapped correlation coefficients between the scores were generated in both groups. Fourteen IPD patients and 19 HC were available for a follow-up study two years later.Results:The mean age of both groups was similar. 58% of IPD patients and 37% of HC were male (p = 0.01). At baseline IPD patients performed less well than HC on all NMD (p value between 0.0001 and 0.02). Out of 91 possible correlations between NMD, 21 were significant in IPD patients and 14 in HC at the level of ≥|0.3|. The mean correlation level was higher in IPD patients than in HC, as evidenced by the higher box plot of correlation coefficients. Visuospatial scores at baseline were predictive of the motor deterioration at the follow-up exam.Conclusion:At early IPD stage various NMS are linked together, although not connected by anatomical networks. Such a clinical NMD connectome suggests almost synchronous disease initiation at different sites as also supported by fMRI findings. Alternatively, there may be compensation-driven interconnectivity of NMD.

Why are ATP-driven microtubule minus-end directed motors critical to plants? An overview of plant multifunctional kinesins.

In plants, microtubule and actin cytoskeletons are involved in key processes including cell division, cell expansion, growth and development, biotic and abiotic stress, tropisms, hormonal signalling as well as cytoplasmic streaming in growing pollen tubes. Kinesin enzymes have a highly conserved motor domain for binding microtubule cytoskeleton assisting these motors to organise their own tracks, the microtubules by using chemical energy of ATP hydrolysis. In addition to this conserved binding site, kinesins possess non-conserved variable domains mediating structural and functional interaction of microtubules with other cell structures to perform various cellular jobs such as chromosome segregation, spindle formation and elongation, transport of organelles as well as microtubules-actins cross linking and microtubules sliding. Therefore, how the non-motor variable regions specify the kinesin function is of fundamental importance for all eukaryotic cells. Kinesins are classified into ~17 known families and some ungrouped orphans, of which ~13 families have been recognised in plants. Kinesin-14 family consisted of plant specific microtubules minus end-directed motors, are much diverse and unique to plants in the sense that they substitute the functions of animal dynein. In this review, we explore the functions of plant kinesins, especially from non-motor domains viewpoint, focussing mainly on recent work on the origin and functional diversity of motors that drive microtubule minus-end trafficking events.