Conclusions on motor control depend on the type of model used to represent the periphery

Within the field of motor control, there is no consensus on which kinematic and kinetic aspects of movements are planned or controlled. Perturbing goal-directed movements is a frequently used tool to answer this question. To be able to draw conclusions about motor control from kinematic responses to perturbations, a model of the periphery (i.e., the skeleton, muscle-tendon complexes, and spinal reflex circuitry) is required. The purpose of the present study was to determine to what extent such conclusions depend on the level of simplification with which the dynamical properties of the periphery are modeled. For this purpose, we simulated fast goal-directed single-joint movement with four existing types of models. We tested how three types of perturbations affected movement trajectory if motor commands remained unchanged. We found that the four types of models of the periphery showed different robustness to the perturbations, leading to different predictions on how accurate motor commands need to be, i.e., how accurate the knowledge of external conditions needs to be. This means that when interpreting kinematic responses obtained in perturbation experiments the level of error correction attributed to adaptation of motor commands depends on the type of model used to describe the periphery

Long-term effects of STN DBS on mood: psychosocial profiles remain stable in a 3-year follow-up

<p>Abstract</p> <p>Background</p> <p>Deep brain stimulation of the subthalamic nucleus significantly improves motor function in patients with severe Parkinson's disease. However, the effects on nonmotor aspects remain uncertain. The present study investigated the effects of subthalamic nucleus deep brain stimulation on mood and psychosocial functions in 33 patients with advanced Parkinson's disease in a three year follow-up.</p> <p>Methods</p> <p>Self-rating questionnaires were administered to 33 patients prior to surgery as well as three, six, twelve and 36 months after surgery.</p> <p>Results</p> <p>In the long run, motor function significantly improved after surgery. Mood and psychosocial functions transiently improved at one year but returned to baseline at 36 months after surgery. In addition, we performed cluster and discriminant function analyses and revealed four distinct psychosocial profiles, which remained relatively stable in the course of time. Two profiles featured impaired psychosocial functioning while the other two of them were characterized by greater psychosocial stability.</p> <p>Conclusion</p> <p>Compared to baseline no worsening in mood and psychosocial functions was found three years after electrode implantation. Moreover, patients can be assigned to four distinct psychosocial profiles that are relatively stable in the time course. Since these subtypes already exist preoperatively the extent of psychosocial support can be anticipatory adjusted to the patients' needs in order to enhance coping strategies and compliance. This would allow early detection and even prevention of potential psychiatric adverse events after surgery. Given adequate psychosocial support, these findings imply that patients with mild psychiatric disturbances should not be excluded from surgery.</p

Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci

Background: A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs). Results: We demonstrate that all CTs are composed of structurally linked chromatin domain clusters (CDCs). In active CTs the periphery of CDCs harbors low-density chromatin enriched with transcriptionally competent markers, called the perichromatin region (PR). The PR borders on a contiguous channel system, the interchromatin compartment (IC), which starts at nuclear pores and pervades CTs. We propose that the PR and macromolecular complexes in IC channels together form the transcriptionally permissive active nuclear compartment (ANC). The Barr body differs from active CTs by a partially collapsed ANC with CDCs coming significantly closer together, although a rudimentary IC channel system connected to nuclear pores is maintained. Distinct Xist RNA foci, closely adjacent to the nuclear matrix scaffold attachment factor-A (SAF-A) localize throughout Xi along the rudimentary ANC. In early differentiating ESCs initial Xist RNA spreading precedes Barr body formation, which occurs concurrent with the subsequent exclusion of RNA polymerase II (RNAP II). Induction of a transgenic autosomal Xist RNA in a male ESC triggers the formation of an `autosomal Barr body' with less compacted chromatin and incomplete RNAP II exclusion. Conclusions: 3D-SIM provides experimental evidence for profound differences between the functional architecture of transcriptionally active CTs and the Barr body. Basic structural features of CT organization such as CDCs and IC channels are however still recognized, arguing against a uniform compaction of the Barr body at the nucleosome level. The localization of distinct Xist RNA foci at boundaries of the rudimentary ANC may be considered as snap-shots of a dynamic interaction with silenced genes. Enrichment of SAF-A within Xi territories and its close spatial association with Xist RNA suggests their cooperative function for structural organization of Xi

Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study.

We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)