Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)

Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm). Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies

Measuring the prediction of observed actions using an occlusion paradigm: Comparing autistic and non‐autistic adults

Action prediction involves observing and predicting the actions of others and plays an important role in social cognition and interacting with others. It is thought to use simulation, whereby the observers use their own motor system to predict the observed actions. As individuals diagnosed with autism are characterized by difficulties understanding the actions of others and motor coordination issues, it is possible that action prediction ability is altered in this population. This study compared action prediction ability between 20 autistic and 22 non‐autistic adults using an occlusion paradigm. Participants watched different videos of a female actor carrying out everyday actions. During each video, the action was transiently occluded by a gray rectangle for 1000 ms. During occlusions, the video was allowed to continue as normal or was moved forward (i.e., appearing to continue too far ahead) or moved backwards (i.e., appearing to continue too far behind). Participants were asked to indicate after each occlusion whether the action continued with the correct timing or was too far ahead/behind. Autistic individuals were less accurate than non‐autistic individuals, particularly when the video was too far behind. A trend analysis suggested that autistic participants were more likely to judge too far behind occlusions as being in time. These preliminary results suggest that prediction ability may be altered in autistic adults, potentially due to slower simulation or a delayed onset of these processes. LAY SUMMARY: When we observe other people performing everyday actions, we use their movements to help us understand and predict what they are doing. In this study, we found that autistic compared to non‐autistic adults were slightly less accurate at predicting other people's actions. These findings help to unpick the different ways that social understanding is affected in autism

Disruption of contralateral inferior parietal cortex by 1 Hz repetitive TMS modulates body sway following unpredictable removal of sway-related fingertip feedback

Contact with an earth-fixed reference augments sway-related feedback and leads to sway reduction during upright standing. We investigated the effect of repetitive transcranial magnetic stimulation (rTMS) over the left hemisphere inferior parietal gyrus (IPG) as well as middle frontal gyrus (MFG) on the progression of sway following right-hand finger tip contact onset and removal. In two experimental sessions, 12 adults received 20 min of 1 Hz rTMS stimulation at 110% passive motor threshold over the left MFG and left IPG, respectively. Before and after each stimulation interval, participants' body sway was assessed in terms of antero-posterior Center-of-Pressure (CoP) velocity. Passive touch onset and removal were timed at random intervals by controlling the vertical position of a contact plate. Progression of sway was evaluated across 6s before to 6s after each contact event. Following both contact onset and removal, a temporary increase in sway above baseline without contact was observed. After removal overshoot was especially prominent. While steady-state sway was not altered by stimulation, rTMS over the left IPG reduced overshoot compared to pre-stimulation; thus, improving sway progression on haptic deprivation. We discuss our finding in the light of altered transient postural disorientation due to intermodal sensory conflict, illusion of backwards falling and tactile attention capture

10-Month-Old Infants Are Sensitive to the Time Course of Perceived Actions: Eye-Tracking and EEG Evidence

Research has shown that infants are able to track a moving target efficiently – even if it is transiently occluded from sight. This basic ability allows prediction of when and where events happen in everyday life. Yet, it is unclear whether, and how, infants internally represent the time course of ongoing movements to derive predictions. In this study, 10-month-old crawlers observed the video of a same-aged crawling baby that was transiently occluded and reappeared in either a temporally continuous or non-continuous manner (i.e., delayed by 500 ms vs. forwarded by 500 ms relative to the real-time movement). Eye movement and rhythmic neural brain activity (EEG) were measured simultaneously. Eye movement analyses showed that infants were sensitive to slight temporal shifts in movement continuation after occlusion. Furthermore, brain activity associated with sensorimotor processing differed between observation of continuous and non-continuous movements. Early sensitivity to an action’s timing may hence be explained within the internal real-time simulation account of action observation. Overall, the results support the hypothesis that 10-month-old infants are well prepared for internal representation of the time course of observed movements that are within the infants’ current motor repertoire

Real-Time Prediction of Observed Action Requires Integrity of the Dorsal Premotor Cortex: Evidence From Repetitive Transcranial Magnetic Stimulation

Studying brain mechanisms underlying the prediction of observed action, the dorsal premotor cortex (PMd) has been suggested a key area. The present study probed this notion using repetitive transcranial magnetic stimulation (rTMS) to test whether interference in this area would affect the accuracy in predicting the time course of object directed actions performed with the right hand. Young and healthy participants observed actions in short videos. These were briefly occluded from view for 600 ms and resumed immediately afterwards. The task was to continue the action mentally and to indicate after each occlusion, whether the action was resumed at the right moment (condition in-time) or shifted. In a first run, single-pulse transcranial magnetic stimulation (sTMS) was delivered over the left primary hand-area during occlusion. In the second run, rTMS over the left PMd was applied during occlusion in half of the participants [experimental group (EG)]. The control group (CG) received sham-rTMS over the same area. Under rTMS, the EG predicted less trials correctly than in the sTMS run. Sham-rTMS in the CG had no effects on prediction. The interference in PMd interacted with the type of manipulation applied to the action’s time course occasionally during occlusion. The performance decrease of the EG was most pronounced in conditions in which the continuations after occlusions were too late in the action’s course. The present results extend earlier findings suggesting that real-time action prediction requires the integrity of the PMd. Different functional roles of this area are discussed. Alternative interpretations consider either simulation of specific motor programming functions or the involvement of a feature-unspecific predictor

A Developmental Framework for Embodiment Research: The Next Step Toward Integrating Concepts and Methods

Embodiment research is at a turning point. There is an increasing amount of data and studies investigating embodiment phenomena and their role in mental processing and functions from across a wide range of disciplines and theoretical schools within the life sciences. However, the integration of behavioral data with data from different biological levels is challenging for the involved research fields such as movement psychology, social and developmental neuroscience, computational psychosomatics, social and behavioral epigenetics, human-centered robotics, and many more. This highlights the need for an interdisciplinary framework of embodiment research. In addition, there is a growing need for a cross-disciplinary consensus on level-specific criteria of embodiment. We propose that a developmental perspective on embodiment is able to provide a framework for overcoming such pressing issues, providing analytical tools to link timescales and levels of embodiment specific to the function under study, uncovering the underlying developmental processes, clarifying level-specific embodiment criteria, and providing a matrix and platform to bridge disciplinary boundaries among the involved research fields

Inhibition des kontraläsionalen dorsalen prämotorischen Kortex zur Verbesserung der motorischen Handfunktion nach Schlaganfall

Lüdemann-Podubecka J, Bösl K, Nowak D. Inhibition des kontraläsionalen dorsalen prämotorischen Kortex zur Verbesserung der motorischen Handfunktion nach Schlaganfall . In: Hermsdörfer J, Stadler W, Johannsen L, eds. The Athlete´s Brain: Neuronale Aspekte motorischer Kontrolle im Sport. Schriften der Deutschen Vereinigung für Sportwissenschaft. Vol 241. Edition Czwalina; 2015: 109-110

Prediction processes during multiple object tracking (MOT):involvement of dorsal and ventral premotor cortices

BACKGROUND: The multiple object tracking (MOT) paradigm is a cognitive task that requires parallel tracking of several identical, moving objects following nongoal-directed, arbitrary motion trajectories. AIMS: The current study aimed to investigate the employment of prediction processes during MOT. As an indicator for the involvement of prediction processes, we targeted the human premotor cortex (PM). The PM has been repeatedly implicated to serve the internal modeling of future actions and action effects, as well as purely perceptual events, by means of predictive feedforward functions. MATERIALS AND METHODS: Using functional magnetic resonance imaging (fMRI), BOLD activations recorded during MOT were contrasted with those recorded during the execution of a cognitive control task that used an identical stimulus display and demanded similar attentional load. A particular effort was made to identify and exclude previously found activation in the PM-adjacent frontal eye fields (FEF). RESULTS: We replicated prior results, revealing occipitotemporal, parietal, and frontal areas to be engaged in MOT. DISCUSSION: The activation in frontal areas is interpreted to originate from dorsal and ventral premotor cortices. The results are discussed in light of our assumption that MOT engages prediction processes. CONCLUSION: We propose that our results provide first clues that MOT does not only involve visuospatial perception and attention processes, but prediction processes as well