Moving In Time: Neurons, Clocks, and Rhythmic Movements

Beek, P.J. [Promotor]Daffertshofer, A. [Copromotor

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Stereo-imaging sensor position localization method and system

The disclosure relates to a method and system wherein sensors on a cap or directly disposed on a head can be localized using a stereo camera. By capturing a plurality of stereo images, the positions of the sensors can be determined with respect to each other. At least a first stereo image having a first set of sensors and a second stereo image having a second set of sensors are captured in a first position respectively a second position of the stereo camera relative to the cap by a relative rotation of the stereo camera around the cap. The first set of sensors and the second set of sensors may have one or more sensors in common. The relative rotation of the stereo camera around the cap can be obtained by at least one of a rotation of the stereo camera around a non-rotating cap and a rotation of the cap with respect to a fixed stereo camera.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin

Tapping with intentional drift

When tapping a desired frequency, subjects tend to drift away from this target frequency. This compromises the estimate of the correlation between inter-tap intervals (ITIs) as predicted by the two-level model of Wing and Kristofferson which consists of an internal timer ('clock') and motor delays. Whereas previous studies on the timing of rhythmic tapping attempted to eliminate drift, we compared the production of three constant frequencies (1.5, 2.0, and 2.5 Hz) to the production of tapping sequences with a linearly decreasing inter-tap interval (ITI) (corresponding to an increase in tapping frequency from 1.5 to 2.5 Hz). For all conditions a synchronization-continuation paradigm was used. Tapping forces and electromyograms of the index-finger flexor and extensor were recorded and ITIs were derived yielding interval variability and model parameters, i.e., clock and motor variances. Electromyographic recordings served to study the influence of tapping frequency on the peripheral part of the tap event. The condition with an increasing frequency was more difficult to perform, as evidenced by an increase in deviation from the intended ITIs. In general, tapping frequency affected force level, inter-tap variability, model parameters, and muscle co-activation. Parameters for the condition with a decreasing ITI were comparable to those found in the constant frequency conditions. That is, although tapping with an intentional drift is different from constant tapping and more difficult to perform, the timing properties of both forms of tapping are remarkably similar and described well by the Wing and Kristofferson model. © 2008 The Author(s)

Differential after-effects of bimanual activity on mirror movements

Using a rhythmic isometric force production paradigm, we investigated the after-effects of in-phase and antiphase bimanual performance on the unintended recruitment of the homologous muscles of the opposite limb during subsequent performance of tasks that were unimanual by design. Electromyograms obtained from the muscles of the opposite limb were analyzed in terms of their amplitude and the distribution of their phase relative to that of the intended movements. Preceding bimanual activity had distinct effects on the relative phase (mean and uniformity) of the structured electromyograms. These were particularly pronounced following performance of the in-phase pattern. These findings are discussed in terms of interhemispheric excitation and inhibition. © 2007 Elsevier Ireland Ltd. All rights reserved

Fatigue-free operation of most body-powered prostheses not feasible for majority of users with trans-radial deficiency

Background: Body-powered prostheses require cable operation forces between 33 and 131 N. The accepted upper limit for fatigue-free long-duration operation is 20% of a users’ maximum cable operation force. However, no information is available on users’ maximum force. Objectives: To quantify users’ maximum cable operation force and to relate this to the fatigue-free force range for the use of body-powered prostheses. Study design: Experimental trial. Methods: In total, 23 subjects with trans-radial deficiencies used a bypass prosthesis to exert maximum cable force three times during 3 s and reported discomfort or pain on a body map. Additionally, subjects’ anthropometric measures were taken to relate to maximum force. Results: Subjects generated forces ranging from 87 to 538 N. Of the 23 subjects, 12 generated insufficient maximum cable force to operate 8 of the 10 body-powered prostheses fatigue free. Discomfort or pain did not correlate with the magnitude of maximum force achieved by the subjects. Nine subjects indicated discomfort or pain. No relationships between anthropometry and maximal forces were found except for maximum cable forces and the affected upper-arm circumference for females. Conclusion: For a majority of subjects, the maximal cable force was lower than acceptable for fatigue-free prosthesis use. Discomfort or pain occurred in ~40% of the subjects, suggesting a suboptimal force transmission mechanism. Clinical relevance: The physical strength of users determines whether a body-powered prosthesis is suitable for comfortable, fatigue-free long-duration use on a daily basis. High cable operation forces can provoke discomfort and pain for some users, mainly in the armpit. Prediction of the users’ strength by anthropometric measures might assist the choice of a suitable prosthesis.Biomechatronics & Human-Machine Contro

A need for a more user-centered design in body powered prostheses

Users of body powered prostheses (BPP) complain about too high operating forces, leading to pain and/or fatigue during or after prosthetic operation. In the worst case nerve and vessel damage can occur [1, 2], leading to nonuse of prostheses. Smit et al. investigated cable forces and displacements required to operate commercially available voluntary closing and voluntary opening hands and hooks [3, 4]. The capacities of prosthetic users to operate these terminal devices remain unknown. Taylor reported in 1954 forces and displacements measured with 50 ‘normal’ subjects for arm flexion (280±24 N; 5.3±1.0 cm), shrug (270±106 N; 5.7±1.5 cm) and arm extension (251±29 N; 5.8±1.7 cm) (mean±SD) [5]. Unfortunately, the measurement procedure is unclear. Moreover, the study reported forces and displacements from isolated movements instead of combinations of movements typically used for BPP operation. Our recent pilot experiments on 10 male subjects (28±2 years old) also without arm defects using a BPP harness revealed average values of 475 N and a peak value of 970 N for one subject. Although these values are higher, it remains unclear if these force levels are sufficient to comfortably operate a BPP, or too low leading to non-use. Importantly, knowing the capacities and limitations of prosthetic users will aid in choosing and redesigning future BPPs to prevent non-use.Biomechatronics & Human-Machine Contro

Frequency response of vestibular reflexes in neck, back, and lower limb muscles

Vestibular pathways form short-latency disynaptic connections with neck motoneurons, whereas they form longer-latency disynaptic and polysynaptic connections with lower limb motoneurons. We quantified frequency responses of vestibular reflexes in neck, back, and lower limb muscles to explain between-muscle differences. Two hypotheses were evaluated: 1) that muscle-specific motor-unit properties influence the bandwidth of vestibular reflexes; and 2) that frequency responses of vestibular reflexes differ between neck, back, and lower limb muscles because of neural filtering. Subjects were exposed to electrical vestibular stimuli over bandwidths of 0–25 and 0–75 Hz while recording activity in sternocleidomastoid, splenius capitis, erector spinae, soleus, and medial gastrocnemius muscles. Coherence between stimulus and muscle activity revealed markedly larger vestibular reflex bandwidths in neck muscles (0–70 Hz) than back (0–15 Hz) or lower limb muscles (0–20 Hz). In addition, vestibular reflexes in back and lower limb muscles undergo low-pass filtering compared with neck-muscle responses, which span a broader dynamic range. These results suggest that the wider bandwidth of head-neck biomechanics requires a vestibular influence on neck-muscle activation across a larger dynamic range than lower limb muscles. A computational model of vestibular afferents and a motoneuron pool indicates that motor-unit properties are not primary contributors to the bandwidth filtering of vestibular reflexes in different muscles. Instead, our experimental findings suggest that pathway-dependent neural filtering, not captured in our model, contributes to these muscle-specific responses. Furthermore, gain-phase discontinuities in the neck-muscle vestibular reflexes provide evidence of destructive interaction between different reflex components, likely via indirect vestibular-motor pathway

EEG as an imaging tool: which inverse method can successfully disentangle sources in proximity?

The accuracy of EEG source localization depends on the choice of the inverse method, the resolution of the forward model, and the signal to noise ratio (SNR) of the recordings. Since we are interested in disentangling sources in proximity, the goal of our study is to examine the sensitivity of spatial resolution of EEG source reconstruction to a wide variety of factors like reconstruction method, SNR, orientation, inter-dipole distance and depth of the simulated dipoles, etc.We simulated time series to resemble waveforms of somatosensory evoked potentials. Inter-dipole distances and different dipole orientations were investigated as well as the effect of (realistic) noise. We employed both spherical and realistic head models. Source reconstruction was realized using a conventional stationary dipole model, MUSIC, self-consistent MUSIC (SC-MUSIC) algorithm, and e-LORETA. In addition to the above mentioned methods, a new approach is tested building upon the e-LORETA solution: the topography of the maximum of the e-LORETA distribution is projected out of the data before calculating the next e-LORETA inverse solution in a iterative process. The quality of fit (or localization) was defined as the distance between the simulated point- sources and either the estimated point-sources or the activity distributions by means of the Euclidean distance or of the Earth Mover’’s Distance, respectively. As expected, inter-dipole distances played an important role in the ability of every method to disentangle the simulated sources. Overall, SC-MUSIC appeared best suited for disentangling the two simulated sources even at high-noise simulations

Cocontraction measured with short-range stiffness was higher in obstetric brachial plexus lesions patients compared to healthy subjects

We suggest short range stiffness (SRS) at the elbow joint as an alternative diagnostic for EMG to assess cocontraction. Elbow SRS is compared between obstetric brachial plexus lesion (OBPL) patients and healthy subjects (cross-sectional study design). Seven controls (median 28years) and five patients (median 31years) isometrically flexed and extended the elbow at rest and three additional torques [2.1,4.3,6.4Nm] while a fast stretch stimulus was applied. SRS was estimated in silico using a neuromechanical elbow model simulating the torque response from the imposed elbow angle. SRS was higher in patients (250±36Nm/rad) than in controls (150±21Nm/rad, p=0.014), except for the rest condition. Higher elbow SRS suggested greater cocontraction in patients compared to controls. SRS is a promising mechanical alternative to assess cocontraction, which is a frequently encountered clinical problem in OBPL due to axonal misrouting.Pathofysiological analysis of movement disorders in relation to functio