Do muscle synergies reduce the dimensionality of behavior?

The muscle synergy hypothesis is an archetype of the notion of Dimensionality Reduction (DR) occurring in the central nervous system due to modular organisation. Towards validating this hypothesis, it is however important to understand if muscle synergies can reduce the state-space dimensionality while suitably achieving task control. In this paper we present a scheme for investigating this reduction, utilising the temporal muscle synergy formulation. Our approach is based on the observation that constraining the control input to a weighted combination of temporal muscle synergies instead constrains the dynamic behaviour of a system in trajectory-specific manner. We compute this constrained reformulation of system dynamics and then use the method of system balancing for quantifying the DR; we term this approach as Trajectory Specific Dimensionality Analysis (TSDA). We then use this method to investigate the consequence of minimisation of this dimensionality for a given task. These methods are tested in simulation on a linear (tethered mass) and a nonlinear (compliant kinematic chain) system; dimensionality of various reaching trajectories is compared when using idealised temporal synergies. We show that as a consequence of this Minimum Dimensional Control (MDC) model, smooth straight-line Cartesian trajectories with bell-shaped velocity profiles are obtained as the solution to reaching tasks in both of the test systems. We also investigate the effect on dimensionality due to adding via-points to a trajectory. The results indicate that a synergy basis and trajectory-specific DR of motor behaviours results from usage of muscle synergy control. The implications of these results for the synergy hypothesis, optimal motor control, developmental skill acquisition and robotics are then discussed

Fatigue, effort perception and central activation failure in chronic stroke survivors: a TMS and fMRI investigation

Fatigue is commonly seen in stroke survivors and the most common manifestation of fatigue is the requirement of high effort for activities of daily life. In this study we set out to identify the neural correlates of perceived effort and central activation failure, a neurophysiological measure correlated with perceived effort. Methods: Twelve chronic stroke survivors participated in this study. Fatigue levels were quantified using the Fatigue Severity Scale -7, perceived effort was quantified using a 1-10 numerical rating scale while performing an isometric biceps hold task, Central Activation Failure was quantified using the modified twitch interpolation technique using Transcranial Magnetic Stimulation and functional Magnetic Resonance Imaging was used to measure blood-oxygen-level dependent signal (BOLD) from the brain while the participant performed a hand grip task. Analysis: Following standard pre-processing procedures for fMRI data using SPM software, co-variance of BOLD signal with perceived effort levels and central activation failure was evaluated. Correlation analysis was performed between measures of fatigue and effort. Results: The main findings of this study were 1) high fatigue was associated with high perceived effort 2) higher perceived effort was associated with greater increase in BOLD fMRI activity in pre-SMA and the ipsilateral inferior frontal gyrus with increasing force 3) greater Central Activation Failure was associated with higher increase in BOLD fMRI activity in bilateral caudate, contralateral superior frontal gyrus and pre-motor cortices with increasing force

Constraining the parameters of globular cluster NGC 1904 from its variable star population

We present the analysis of 11 nights of V and I time-series observations of the globular cluster NGC 1904 (M 79). Using this we searched for variable stars in this cluster and attempted to refine the periods of known variables, making use of a time baseline spanning almost 8 years. We use our data to derive the metallicity and distance of NGC 1904. We used difference imaging to reduce our data to obtain high-precision light curves of variable stars. We then estimated the cluster parameters by performing a Fourier decomposition of the light curves of RR Lyrae stars for which a good period estimate was possible. We also derive an estimate for the age of the cluster by fitting theoretical isochrones to our colour-magnitude diagram (CMD). Out of 13 stars previously classified as variables, we confirm that 10 are bona fide variables. We cannot detect variability in one other within the precision of our data, while there are two which are saturated in our data frames, but we do not find sufficient evidence in the literature to confirm their variability. We also detect a new RR Lyrae variable, giving a total number of confirmed variable stars in NGC 1904 of 11. Using the Fourier parameters, we find a cluster metallicity [Fe/H]_ZW=-1.63 +- 0.14, or [Fe/H]_UVES=-1.57 \pm 0.18, and a distance of 13.3 +- 0.4 kpc (using RR0 variables) or 12.9 kpc (using the one RR1 variable in our sample for which Fourier decomposition was possible).Comment: 14 pages, 11 figures, accepted for publication in A&

Solvent mediated centric/non-centric polymorph pairs of an indole derivative: subtle variation of C-HO hydrogen bonds and C-Hπ interactions

Centric (P21/n) and non-centric (P21) polymorphic pairs of biologically active 1-(4-fluorophenyl)-6,6-dimethyl-2-phenyl-1,5,6,7-tetrahydro-4H-indol-4-one crystallized from different solvents have been elucidated via single crystal and powder X-ray diffraction studies, morphological observations and calorimetric measurements. C-H...O hydrogen bonding and weak intermolecular C-H...π interactions generate distinct packing features in the two forms

Development of joint stiffness and learnability

One of the fundamental problems in developmental robotics relates to the progressive spontaneous acquisition of motor abilities by an organism. Throughout this process, the speed of acquiring abilities, which we term 'learnability', is strongly limited by the dimensionality of the sensori-motor space; this in turn could affect the survival of an organism. In this paper, we tackle the problem of dimensional change during development using a framework of control dimensionality reduction based on nonlinear system balancing. Using a set of internal models of behaviour of increasing dimensionality, we show that joint-stiffness regulation can be used to ensure optimal development of motor skills. This is quantified as a maximisation of internal model accuracy at intermediate stages of learning. We test our approach in a simulation of a human arm modelled as a 2 link kinematic chain performing point-to-point and via-point reaching tasks. We then analyse optimal joint-stiffness development towards facilitating effective dimensional change and compare two strategies, (i) uniform development and (ii) proximo-distal development, i.e. variation of only the distal joint stiffness. Our results indicate that latter strategy, although lower in accuracy is a simpler approach towards learnability regulation. The implications of the model and the results for biological motor control and robotics are then discussed

Neural effective connectivity explains subjective fatigue in stroke

Persistent fatigue is a major debilitating symptom in many psychiatric and neurological conditions, including stroke. Post-stroke fatigue has been linked to low corticomotor excitability. Yet, it remains elusive what the neuronal mechanisms are that underlie motor cortex excitability and chronic persistence of fatigue. In this cross-sectional observational study, in two experiments we examined a total of 59 non-depressed stroke survivors with minimal motoric and cognitive impairments using 'resting state' magnetic resonance imaging (rs-fMRI), single-pulse and paired-pulse transcranial magnetic stimulation (pp-TMS). In the first session of Experiment 1, we assessed resting motor thresholds (RMTs) - a typical measure of cortical excitability-by applying TMS to the primary motor cortex (M1) and measuring motor-evoked potential in the hand affected by stroke. In the second session, we measured their brain activity with rs-fMRI to assess effective connectivity interactions at rest. In Experiment 2 we examined effective inter-hemispheric connectivity in an independent sample of patients using pp-TMS. We also assessed the levels of non-exercise induced, persistent fatigue using Fatigue Severity Scale (FSS-7), a self-report questionnaire which has been widely applied and validated across different conditions. We employed spectral dynamic causal modelling (sp-DCM) in Experiment 1 and pp-TMS in Experiment 2 to characterise how neuronal effective connectivity relates to self-reported post-stroke fatigue. In a multiple regression we used the balance in inhibitory connectivity between homologue regions in M1 as the main predictor, and have included lesioned hemisphere, RMT and levels of depression as additional predictors. Our novel index of inter-hemispheric inhibition balance was a significant predictor of post-stroke fatigue in Experiment 1 (β  =  1.524, p = 7.56e-05, CI[0.921, 2.127]) and in Experiment 2 (β  =  0.541, p = 0.049, CI[0.002, 1.080]). In experiment 2, depression scores and corticospinal excitability, a measure associated with subjective fatigue, also significantly accounted for variability in fatigue. We suggest that the balance in inter-hemispheric inhibitory effects between primary motor regions can explain subjective post-stroke fatigue. Findings provide novel insights into neural mechanisms that underlie persistent fatigue

Predicting gene ontology annotations of orphan GWAS genes using protein-protein interactions

Background: The number of genome-wide association studies (GWAS) has increased rapidly in the past couple of years, resulting in the identification of genes associated with different diseases. The next step in translating these findings into biomedically useful information is to find out the mechanism of the action of these genes. However, GWAS studies often implicate genes whose functions are currently unknown; for example, MYEOV, ANKLE1, TMEM45B and ORAOV1 are found to be associated with breast cancer, but their molecular function is unknown.Results: We carried out Bayesian inference of Gene Ontology (GO) term annotations of genes by employing the directed acyclic graph structure of GO and the network of protein-protein interactions (PPIs). The approach is designed based on the fact that two proteins that interact biophysically would be in physical proximity of each other, would possess complementary molecular function, and play role in related biological processes. Predicted GO terms were ranked according to their relative association scores and the approach was evaluated quantitatively by plotting the precision versus recall values and F-scores (the harmonic mean of precision and recall) versus varying thresholds. Precisions of ~58% and ~ 40% for localization and functions respectively of proteins were determined at a threshold of ~30 (top 30 GO terms in the ranked list). Comparison with function prediction based on semantic similarity among nodes in an ontology and incorporation of those similarities in a k-nearest neighbor classifier confirmed that our results compared favorably.Conclusions: This approach was applied to predict the cellular component and molecular function GO terms of all human proteins that have interacting partners possessing at least one known GO annotation. The list of predictions is available at http://severus.dbmi.pitt.edu/engo/GOPRED.html. We present the algorithm, evaluations and the results of the computational predictions, especially for genes identified in GWAS studies to be associated with diseases, which are of translational interest. © 2014 Kuppuswamy et al.; licensee BioMed Central Ltd

Chemistry of 1-Fluoro-2,3,4-triphenylcyclobutadiene Dimers

The reaction of 2,4-dichloro-1,1-difluoro-3-phenyl-2-cyclobutene 1 with excess phenyllithium and subsequent transformations of the products have been reinvestigated. The phenyllithium reaction appears to proceed through the intermediacy of a fluorotriphenylcyclobutadiene 2 to produce a well-characterized dimeric trans-hexaphenyldifluorotricyclooctadiene 3a. Subsequent transformations of 3a gave a pentaphenyldihydrodifluoropentalene 4, which on acid hydrolysis formed a pentaphenyldihydropentalenone 5. When 3a was photolyzed in benzene, after purification, it afforded 6, an isomer of 5, probably by way of 7, an isomer of 4. Thermolysis of 3a also provided, in low yield, a substance believed to be a pentaphenylfluorophenanthrene 8. Along with isolation of 3a, and probably arising from a different isomer of the 3 family, was a pentaphenylfluorophenanthrene 9, which was suspected of being an isomer of 8. Single-crystal X-ray studies were used to derive structures for 4, 5, 6, and 9. Formation of the unusual and intriguing transformation products has at least been rationalized