The brain is able to determine angular self-motion from visual, vestibular, and kinesthetic information. There is compelling evidence that both humans and non-human primates integrate visual and ...inertial (i.e., vestibular and kinesthetic) information in a statistically optimal fashion when discriminating heading direction. In the present study, we investigated whether the brain also integrates information about angular self-motion in a similar manner. Eight participants performed a 2IFC task in which they discriminated yaw-rotations (2-s sinusoidal acceleration) on peak velocity. Just-noticeable differences (JNDs) were determined as a measure of precision in unimodal inertial-only and visual-only trials, as well as in bimodal visual–inertial trials. The visual stimulus was a moving stripe pattern, synchronized with the inertial motion. Peak velocity of comparison stimuli was varied relative to the standard stimulus. Individual analyses showed that data of three participants showed an increase in bimodal precision, consistent with the optimal integration model; while data from the other participants did not conform to maximum-likelihood integration schemes. We suggest that either the sensory cues were not perceived as congruent, that integration might be achieved with fixed weights, or that estimates of visual precision obtained from non-moving observers do not accurately reflect visual precision during self-motion.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Without visual feedback, humans perceive tilt when experiencing a sustained linear acceleration. This tilt illusion is commonly referred to as the somatogravic illusion. Although the physiological ...basis of the illusion seems to be well understood, the dynamic behavior is still subject to discussion. In this study, the dynamic behavior of the illusion was measured experimentally for three motion profiles with different frequency content. Subjects were exposed to pure centripetal accelerations in the lateral direction and were asked to indicate their tilt percept by means of a joystick. Variable-radius centrifugation during constant angular rotation was used to generate these motion profiles. Two self-motion perception models were fitted to the experimental data and were used to obtain the time constant of the somatogravic illusion. Results showed that the time constant of the somatogravic illusion was on the order of two seconds, in contrast to the higher time constant found in fixed-radius centrifugation studies. Furthermore, the time constant was significantly affected by the frequency content of the motion profiles. Motion profiles with higher frequency content revealed shorter time constants which cannot be explained by self-motion perception models that assume a fixed time constant. Therefore, these models need to be improved with a mechanism that deals with this variable time constant. Apart from the fundamental importance, these results also have practical consequences for the simulation of sustained accelerations in motion simulators.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Prefrontal and parietal areas are thought to orchestrate decision making.•We investigate whether this applies to decisions on self-motion using fNIRS.•Parietal activity predicts judgments on ...whole-body yaw rotation intensity.•Results suggest parietal activity reflects modality-independent decision variables.
Prominent accounts of decision making state that decisions are made on the basis of an accumulation of sensory evidence, orchestrated by networks of prefrontal and parietal neural populations. Here we assess whether these findings generalize to decisions on self-motion.
Participants were presented with whole body yaw rotations of different durations in a 2-Interval-Forced-Choice paradigm, and tasked to discriminate motions on the basis of their amplitude. The cortical hemodynamic response was recorded using functional near-infrared spectroscopy (fNIRS) while participants were performing the task.
The imaging data was used to predict the specific response on individual experimental trials, and to predict whether the comparison stimulus would be judged larger than the reference. Classifier performance on the former variable was negligible. However, considerable performance was achieved for the latter variable, specifically using parietal imaging data. The findings provide support for the notion that activity in the parietal cortex reflects modality independent decision variables that represent the strength of the neural evidence in favor of a decision. The results are encouraging for the use of fNIRS as a method to perform neuroimaging in moving individuals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
In the present study, we investigated whether the perception of heading of linear self-motion can be explained by Maximum Likelihood Integration (MLI) of visual and non-visual sensory cues. MLI ...predicts smaller variance for multisensory judgments compared to unisensory judgments. Nine participants were exposed to visual, inertial, or visual-inertial motion conditions in a moving base simulator, capable of accelerating along a horizontal linear track with variable heading. Visual random-dot motion stimuli were projected on a display with a 40° horizontal × 32° vertical field of view (FoV). All motion profiles consisted of a raised cosine bell in velocity. Stimulus heading was varied between 0 and 20°. After each stimulus, participants indicated whether perceived self-motion was straight-ahead or not. We fitted cumulative normal distribution functions to the data as a psychometric model and compared this model to a nested model in which the slope of the multisensory condition was subject to the MLI hypothesis. Based on likelihood ratio tests, the MLI model had to be rejected. It seems that the imprecise inertial estimate was weighed relatively more than the precise visual estimate, compared to the MLI predictions. Possibly, this can be attributed to low realism of the visual stimulus. The present results concur with other findings of overweighing of inertial cues in synthetic environments.
This study investigates the effects of anthropometric attributes, biological sex, and posture on translational body kinematic responses in translational vibrations. In total, 35 participants were ...recruited. Perturbations were applied on a standard car seat using a motion-based platform with 0.1 to 12.0 Hz random noise signals, with 0.3 m/s2 rms acceleration, for 60 seconds. Multiple linear regression models (three basic models and one advanced model, including interactions between predictors) were created to determine the most influential predictors of peak translational gains in the frequency domain per body segment (pelvis, trunk, and head). The models introduced experimentally manipulated factors (motion direction, posture, measured anthropometric attributes, and biological sex) as predictors. Effects of included predictors on the model fit were estimated. Basic linear regression models could explain over 70% of peak body segments' kinematic body response (where the R2 adjusted was 0.728). The inclusion of additional predictors (posture, body height and weight, and biological sex) did enhance the model fit, but not significantly (R2 adjusted was 0.730). The multiple stepwise linear regression, including interactions between predictors, accounted for the data well with an adjusted R2 of 0.907. The present study shows that perturbation direction and body segment kinematics are crucial factors influencing peak translational gains. Besides the body segments' response, perturbation direction was the strongest predictor. Adopted postures and biological sex do not significantly affect kinematic responses.
Primary IgA nephropathy (IgAN) is associated with elevated levels of circulating IgA and is characterized by deposition of primarily IgA1 in the renal mesangium. It has not yet been clarified which ...mechanisms govern the deposition of IgA1 in the mesangium. One of the factors which may play a role in trapping of IgA in the mesangial area is the interaction of IgA with specific IgA receptors (Fc alphaR, CD89) on the mesangial cells.
In the present study IgA derived from patients with IgAN and controls was investigated for its interaction with human CD89, expressed on the surface of the murine B cell line IIA1.6.
IgA binding to CD89 expressing cells was specific, concentration dependent and binding of dIgA and pIgA occurred in a more efficient fashion than that of mIgA. IgA binding to CD89 directly from serum of patients compared to controls showed no significant difference. However these experiments are affected by differences in IgA concentration and combinations of different sizes of IgA. Using purified fractions of mIgA, dIgA, and pIgA isolated from serum, a significantly reduced binding of mIgA to CD89 from patients compared to controls was observed. Finally, the binding of aIgA2 to CD89 was less inhibited using mIgA from patients with IgAN compared to controls.
The reduced binding of mIgA to CD89 seems to contradict a direct role for CD89 in deposition of IgA. However reduced binding of mIgA to CD89 may affect IgA clearance, leading to higher serum IgA. Furthermore, since it has been demonstrated that mIgA can interfere with binding of di- and pIgA, CD89 could still contribute to pIgA deposition in the mesangial area.
Objective
To test whether polygenic risk score for schizophrenia (PRS‐S) interacts with childhood adversity and daily‐life stressors to influence momentary mental state domains (negative affect, ...positive affect, and subtle psychosis expression) and stress‐sensitivity measures.
Methods
The data were retrieved from a general population twin cohort including 593 adolescents and young adults. Childhood adversity was assessed using the Childhood Trauma Questionnaire. Daily‐life stressors and momentary mental state domains were measured using ecological momentary assessment. PRS‐S was trained on the latest Psychiatric Genetics Consortium schizophrenia meta‐analysis. The analyses were conducted using multilevel mixed‐effects tobit regression models.
Results
Both childhood adversity and daily‐life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS‐S was only associated with increased positive affect. No gene–environment correlation was detected. There is novel evidence for interaction effects between PRS‐S and childhood adversity to influence momentary mental states negative affect (b = 0.07, P = 0.013), positive affect (b = −0.05, P = 0.043), and subtle psychosis expression (b = 0.11, P = 0.007) and stress‐sensitivity measures.
Conclusion
Exposure to childhood adversities, particularly in individuals with high PRS‐S, is pleiotropically associated with emotion dysregulation and psychosis proneness.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
We evaluated the dose requirements for sustained in vivo activity of ofatumumab, a human anti‐CD20 antibody under development for the treatment of B cell‐mediated diseases. In a mouse ...xenograft model, a single dose, resulting in an initial plasma antibody concentration of 5 μg/ml, which was expected to result in full target saturation, effectively inhibited human B‐cell tumour development. Tumour growth resumed when plasma concentrations dropped below levels that are expected to result in half‐maximal saturation. Notably, tumour load significantly impacted antibody pharmacokinetics. In monkeys, initial depletion of circulating and tissue residing B cells required relatively high‐dose levels. Re‐population of B‐cell compartments, however, only became detectable when ofatumumab levels dropped below 10 μg/ml. We conclude that, once saturation of CD20 throughout the body has been reached by high initial dosing, plasma concentrations that maintain target saturation on circulating cells (5–10 μg/ml) are probably sufficient for sustained biological activity. These observations may provide a rationale for establishing dosing schedules for maintenance immunotherapy following initial depletion of CD20 positive (tumour) cells.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Introduction
Prior evidence suggests that men and women might be differentially susceptible to distinct types of childhood adversity (CA), but research on gender-specific associations between CA ...subtypes and psychiatric symptoms is limited.
Objectives
To test the gender-specific associations of CA subtypes and psychiatric symptoms in the general population.
Methods
Data from 791 twins and siblings from the TwinssCan project were used. Psychopathology and CA exposure were assessed using the Symptom Checklist-90 Revised (SCL-90) and the Childhood Trauma Questionnaire (CTQ), respectively. The associations between the total CTQ scores and SCL-90 scores (i.e. total SCL-90, psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety) were tested in men and women separately. The associations between the five CA subtypes (i.e. physical abuse, emotional abuse, sexual abuse, physical neglect, and emotional neglect) and total SCL-90 were tested in a mutually adjusted model. As exploratory analyses, the associations between all CA subtypes and the nine SCL-90 subdomain scores were similarly tested. The regression coefficients between men and women were compared using Chow’s test. All models were adjusted for age and family structure.
Results
Total CTQ was significantly associated with total SCL-90 in men (
B
= 0.013,
SE
= 0.003,
P
< .001) and women (
B
= 0.011,
SE
= 0.002,
P
< .001). The associations with the nine symptom domains were also significant in both genders (
P
< .001). No significant gender differences in the regression coefficients of total CTQ were detected. The analyses of CA subtypes showed a significant association between emotional abuse and total SCL-90 in women (
B
= 0.173,
SE
= 0.030,
P
< .001) and men (
B
= 0.080,
SE
= 0.035,
P
= .023), but the association was significantly stronger in women (ꭓ
2
(1) = 4.10,
P
= .043). The association of sexual abuse and total SCL-90 was only significant in women (
B
= 0.217,
SE
= 0.053,
P
< .001). The associations of emotional neglect (
B
= 0.061,
SE
= 0.027,
P
= .026) and physical neglect (
B
= 0.167,
SE
= 0.043,
P
< .001) with total SCL-90 were only significant in men. The explorative analyses of SCL-90 subdomains revealed significant associations of emotional abuse with all nine symptom domains and of sexual abuse with seven symptom domains in women. Significant associations of physical neglect with six symptom domains and of emotional neglect with depression were also detected in men. No other significant associations between CT subtypes and total SCL-90 or symptom domain scores were observed in men and women.
Conclusions
CA exposure was associated with diverse psychopathology similarly in both genders. However, women are more sensitive to abuse, but men are more sensitive to neglect. Gender-specific influences of CA subtypes on psychopathology should be considered in future studies.
Disclosure of Interest
None Declared
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