Continuous sweep versus discrete step protocols for studying effects of wearable robot assistance magnitude

Background: Different groups developed wearable robots for walking assistance, but there is still a need for methods to quickly tune actuation parameters for each robot and population or sometimes even for individual users. Protocols where parameters are held constant for multiple minutes have traditionally been used for evaluating responses to parameter changes such as metabolic rate or walking symmetry. However, these discrete protocols are time-consuming. Recently, protocols have been proposed where a parameter is changed in a continuous way. The aim of the present study was to compare effects of continuously varying assistance magnitude with a soft exosuit against discrete step conditions. Methods: Seven participants walked on a treadmill wearing a soft exosuit that assists plantarflexion and hip flexion. In Continuous-up, peak exosuit ankle moment linearly increased from approximately 0 to 38% of biological moment over 10 min. Continuous-down was the opposite. In Discrete, participants underwent five periods of 5 min with steady peak moment levels distributed over the same range as Continuous-up and Continuous-down. We calculated metabolic rate for the entire Continuous-up and Continuous-down conditions and the last 2 min of each Discrete force level. We compared kinematics, kinetics and metabolic rate between conditions by curve fitting versus peak moment. Results: Reduction in metabolic rate compared to Powered-off was smaller in Continuous-up than in Continuousdown at most peak moment levels, due to physiological dynamics causing metabolic measurements in Continuousup and Continuous-down to lag behind the values expected during steady-state testing. When evaluating the average slope of metabolic reduction over the entire peak moment range there was no significant difference between Continuous-down and Discrete. Attempting to correct the lag in metabolics by taking the average of Continuous-up and Continuous-down removed all significant differences versus Discrete. For kinematic and kinetic parameters, there were no differences between all conditions. Conclusions: The finding that there were no differences in biomechanical parameters between all conditions suggests that biomechanical parameters can be recorded with the shortest protocol condition (i.e. single Continuous directions). The shorter time and higher resolution data of continuous sweep protocols hold promise for the future study of human interaction with wearable robots

Preventing emerging infectious diseases : a strategy for the 21st century : overview of the updated CDC plan

Societal, technological, and environmental factors continue to have a dramatic effect on infectious diseases worldwide, facilitating the emergence of new diseases and the reemergence of old ones, sometimes in drug-resistant forms. Modern demographic and ecologic conditions that favor the spread of infectious diseases include rapid population growth; increasing poverty and urban migration; more frequent movement across international boundaries by tourists, workers, immigrants, and refugees; alterations in the habitats of animals and arthropods that transmit disease; increasing numbers of persons with impaired host defenses; and changes in the way that food is processed and distributed. Several recent health events underscore the need for a public health system ready to address whatever disease problems that might arise. For example, in 1997, an avian strain of influenza that had never before infected humans began to kill previously healthy persons in Hong Kong, and strains of Sta phylococcus aureus with diminished susceptibility to the antibiotic vancomycin were reported in Japan and the United States. In addition, researchers recently discovered that a strain of the virus that causes acquired immunodeficiency syndrome (AIDS) had been infecting humans for at least 20 years before AIDS emerged as a worldwide epidemic. Preventing Emerging Infectious Diseases: A Strategy for the 21st Century describes CDC's plan to combat today's infectious diseases and prevent those of tomorrow. It represents the second phase of the effort launched in 1994 with the publication of CDC's Addressing Emerging Infectious Disease Threats: A Prevention Strategy for the United States. This overview of the updated plan outlines specific objectives under four major goals: a) surveillance and response, b) applied research, c) infrastructure and training, and d) prevention and control. Achieving these objectives will enhance understanding of infectious diseases and bolster their detection, control, and prevention. The plan also targets nine categories of problems that cause human suffering and place a burden on society. The aim of this plan is to build a stronger, more flexible U.S. public health system that is well-prepared to respond to known disease problems, as well as to address the unexpected, whether it be an influenza pandemic, a disease caused by an unknown organism, or a bioterrorist attack. The implementation of this plan will require the dedicated efforts of many partners, including state and local health departments, other federal agencies, professional societies, universities, research institutes, health-care providers and organizations, the World Health Organization, and many other domestic and international organizations and groups.September 11, 1998.The following CDC staff members prepared this report: Suzanne Binder, Alexandra M. Levitt, National Center for Infectious Diseases, and National Center for Infectious Diseases Plan Steering Committee.Includes bibliographical references.199

A Comparison of Stimulus Presentation Methods in Temporal Discrimination Testing

The temporal discrimination threshold (TDT) is the shortest time interval at which an individual detects two stimuli to be asynchronous (normal  =  30-50 ms). It has been shown to be abnormal in patients with disorders affecting the basal ganglia including adult onset idiopathic focal dystonia (AOIFD). Up to 97% of patients have an abnormal TDT with age- and sex-related penetrance in unaffected relatives, demonstrating an autosomal dominant inheritance pattern. These findings support the use of the TDT as a pre-clinical biomarker for AOIFD. The usual stimulus presentation method involves the presentation of progressively asynchronous stimuli; when three sequential stimuli are reported asynchronous is taken as a participant\u27s TDT. To investigate the robustness of the \u27staircase\u27 method of presentation, we introduced a method of randomised presentation order to explore any potential \u27learning effect\u27 that may be associated with this existing method. The aim of this study was to investigate differences in temporal discrimination using two methods of stimulus presentation. Thirty healthy volunteers were recruited to the study (mean age 33.73  ±  3.4 years). Visual and tactile TDT testing using a staircase and randomised method of presentation order was carried out in a single session. There was a strong relationship between the staircase and random method for TDT values. This observed consistency between testing methods suggests that the existing experimental approach is a robust method of recording an individual\u27s TDT. In addition, our newly devised randomised paradigm is a reproducible and more efficient method for data acquisition in the clinic setting. However, the two presentation methods yield different absolute TDT results and either of the two methods should be used uniformly in all participants in any one particular study. doi: 10.1088/1361-6579/38/2/N5

A Headset Method for Measuring the Visual Temporal Discrimination Threshold in Cervical Dystonia

Background: The visual temporal discrimination threshold (TDT) is the shortest time interval at which one can determine two stimuli to be asynchronous and meets criteria for a valid endophenotype in adult‐onset idiopathic focal dystonia, a poorly penetrant disorder. Temporal discrimination is assessed in the hospital laboratory; in unaffected relatives of multiplex adult‐onset dystonia patients distance from the hospital is a barrier to data acquisition. We devised a portable headset method for visual temporal discrimination determination and our aim was to validate this portable tool against the traditional laboratory‐based method in a group of patients and in a large cohort of healthy controls. Methods: Visual TDTs were examined in two groups 1) in 96 healthy control participants divided by age and gender, and 2) in 33 cervical dystonia patients, using two methods of data acquisition, the traditional table‐top laboratory‐based system, and the novel portable headset method. The order of assessment was randomized in the control group. The results obtained by each technique were compared. Results: Visual temporal discrimination in healthy control participants demonstrated similar age and gender effects by the headset method as found by the table‐top examination. There were no significant differences between visual TDTs obtained using the two methods, both for the control participants and for the cervical dystonia patients. Bland–Altman testing showed good concordance between the two methods in both patients and in controls. Discussion: The portable headset device is a reliable and accurate method for visual temporal discrimination testing for use outside the laboratory, and will facilitate increased TDT data collection outside of the hospital setting. This is of particular importance in multiplex families where data collection in all available members of the pedigree is important for exome sequencing studies

Measurement & Analysis of the Temporal Discrimination Threshold Applied to Cervical Dystonia

The temporal discrimination threshold (TDT) is the shortest time interval at which an observer can discriminate two sequential stimuli as being asynchronous (typically 30-50 ms). It has been shown to be abnormal (prolonged) in neurological disorders, including cervical dystonia, a phenotype of adult onset idiopathic isolated focal dystonia. The TDT is a quantitative measure of the ability to perceive rapid changes in the environment and is considered indicative of the behavior of the visual neurons in the superior colliculus, a key node in covert attentional orienting. This article sets out methods for measuring the TDT (including two hardware options and two modes of stimuli presentation). We also explore two approaches of data analysis and TDT calculation. The application of the assessment of temporal discrimination to the understanding of the pathogenesis of cervical dystonia and adult onset idiopathic isolated focal dystonia is also discussed

Neural Correlates of Abnormal Temporal Discrimination in Unaffected Relatives of Cervical Dystonia Patients

Background: An abnormal temporal discrimination threshold in cervical dystonia (CD) is considered to be a mediational endophenotype; in unaffected relatives it is hypothesized to indicate non-manifesting gene carriage. The pathogenesis underlying this condition remains unknown. Investigation of the neural networks involved in disordered temporal discrimination may highlight its pathomechanisms.Objective: To examine resting state brain function in unaffected relatives of CD patients with normal and abnormal temporal discrimination. We hypothesized that the endophenotype, an abnormal temporal discrimination, would manifest as altered connectivity in relatives in regions associated with CD, thereby illuminating the neural substrates of the link between temporal discrimination and CD.Methods: Rs-fMRI data was analyzed from two sex- and age-matched cohorts: 16 unaffected relatives of CD patients with normal temporal discrimination and 16 with abnormal temporal discrimination. Regional and whole brain functional connectivity measures were extracted via Independent Component Analysis (ICA), Regional Homogeneity (ReHo), and Amplitude of Low Frequency (ALFF) analyses.Results: Our ICA analysis revealed increased connectivity within both the executive control and cerebellar networks and decreased connectivity within the sensorimotor network in relatives with abnormal temporal discrimination when compared to relatives with normal temporal discrimination. The ReHo and ALFF analyses complimented these results and demonstrated connectivity differences in areas corresponding to motor planning, movement coordination, visual information processing, and eye movements in unaffected relatives with abnormal temporal discrimination.Conclusion: Disordered connectivity in unaffected relatives with abnormal temporal discrimination illuminates neural substrates underlying endophenotype expression and supports the hypothesis that genetically determined aberrant connectivity, when later coupled with unknown environmental triggers, may lead to disease penetrance

Menstrual Cycle and the Temporal Discrimination Threshold

The temporal discrimination threshold (TDT) is a proposed pre-clinical biomarker (endophenotype) for adult onset isolated focal dystonia (AOIFD). Age- and sex-related effects on temporal discrimination demonstrate that women, before the age of 40 years, have faster temporal discrimination than men but their TDTs worsen with age at almost three times the rate of men. Thus after 40 years the TDT in women is progressively worse than in men. AOIFD is an increasingly female-predominant disorder after the age of 40; it is not clear whether this age-related sexually-dimorphic difference observed for both the TDT and sex ratio at disease onset in AOIFD is a hormonal or chromosomal effect. The aim of this study was to examine temporal discrimination at weekly intervals during two consecutive menstrual cycles in 14 healthy female volunteers to determine whether physiological hormonal changes affected temporal discrimination. We observed no significant differences in weekly temporal discrimination threshold values during the menstrual cycles and no significant correlation with the menstrual cycle stage. This observed stability of temporal discrimination during cyclical hormonal change raises interesting questions concerning the age-related sexually-dimorphic decline observed in temporal discrimination. Our findings pave the way for future studies exploring potential pathomechanisms for this age-related deterioration

Disrupted Superior Collicular Activity May Reveal Crvical Dystonia Disease Pathomechanisms

Cervical dystonia is a common neurological movement disorder characterised by muscle contractions causing abnormal movements and postures afecting the head and neck. The neural networks underpinning this condition are incompletely understood. While animal models suggest a role for the superior colliculus in its pathophysiology, this link has yet to be established in humans. The present experiment was designed to test the hypothesis that disrupted superior collicular processing is evident in afected patients and in relatives harbouring a disease-specifc endophenotype (abnormal temporal discrimination). The study participants were 16 cervical dystonia patients, 16 unafected frst-degree relatives with abnormal temporal discrimination, 16 unafected frst-degree relatives with normal temporal discrimination and 16 healthy controls. The response of participant’s superior colliculi to looming stimuli was assessed by functional magnetic resonance imaging. Cervical dystonia patients and relatives with abnormal temporal discrimination demonstrated (i) signifcantly reduced superior collicular activation for whole brain and region of interest analysis; (ii) a statistically signifcant negative correlation between temporal discrimination threshold and superior collicular peak values. Our results support the hypothesis that disrupted superior collicular processing is involved in the pathogenesis of cervical dystonia. These fndings, which align with animal models of cervical dystonia, shed new light on pathomechanisms in humans

Disrupted Superior Collicular Activity May Reveal Cervical Dystonia Disease Pathomechanisms

Cervical dystonia is a common neurological movement disorder characterised by muscle contractions causing abnormal movements and postures affecting the head and neck. The neural networks underpinning this condition are incompletely understood. While animal models suggest a role for the superior colliculus in its pathophysiology, this link has yet to be established in humans. The present experiment was designed to test the hypothesis that disrupted superior collicular processing is evident in affected patients and in relatives harbouring a disease-specific endophenotype (abnormal temporal discrimination). The study participants were 16 cervical dystonia patients, 16 unaffected first-degree relatives with abnormal temporal discrimination, 16 unaffected first-degree relatives with normal temporal discrimination and 16 healthy controls. The response of participant’s superior colliculi to looming stimuli was assessed by functional magnetic resonance imaging. Cervical dystonia patients and relatives with abnormal temporal discrimination demonstrated (i) significantly reduced superior collicular activation for whole brain and region of interest analysis; (ii) a statistically significant negative correlation between temporal discrimination threshold and superior collicular peak values. Our results support the hypothesis that disrupted superior collicular processing is involved in the pathogenesis of cervical dystonia. These findings, which align with animal models of cervical dystonia, shed new light on pathomechanisms in humans

Slowed luminance reaction times in cervical dystonia: disordered superior colliculus processing

Background: Abnormal temporal discrimination in cervical dystonia is hypothesised to be due to disrupted processing in the superior colliculus. The fast, luminance-based, retino-tectal pathway, projects to the superior colliculus; chromatic stimuli responses, via the retino-geniculo-calcarine pathway, are up to 30ms longer. Methods: In 20 cervical dystonia and 20 age-matched control participants, we compared reaction times to two flashing visual stimuli: (i) a chromatic annulus and (ii) a luminant, non-coloured annulus. Participants pressed a joystick control when they perceived the annulus flashing. Results: Reaction times in control participants were 20ms significantly faster in the luminant condition than the chromatic (p= 0.017). Patients with cervical dystonia had no reaction time advantage in response to the luminant stimulus. Conclusion: Cervical dystonia patients (compared to control participants) demonstrated no reduction in their reaction time to luminant stimuli, processed through the retino-tectal pathway. This finding is consistent with superior colliculus dysfunction in cervical dystonia