Tactile localization biases are modulated by gaze direction

Identifying the spatial location of touch on the skin surface is a fundamental function of our somatosensory system. Despite the fact that stimulation of even single mechanoreceptive afferent fibres is sufficient to produce clearly localised percepts, tactile localisation can be modulated also by higher-level processes such as body posture. This suggests that tactile events are coded using multiple representations using different coordinate systems. Recent reports provide evidence for systematic biases on tactile localisation task, which are thought to result from a supramodal representation of the skin surface. While the influence of non-informative vision of the body and gaze direction on tactile discrimination tasks has been extensively studied, their effects on tactile localisation tasks remain largely unexplored. To address this question, participants performed a tactile localization task on their left hand under different visual conditions by means of a mirror box; in the mirror condition a single stimulus was delivered on participants’ hand while the reflexion of the right hand was seen through the mirror; in the object condition participants looked at a box through the mirror, and in the right hand condition participants looked directly at their right hand. Participants reported the location of the tactile stimuli using a silhouette of a hand. Results showed a shift in the localization of the touches towards the tip of the fingers (distal bias) and the thumb (radial biases) across conditions. Critically, distal biases were reduced when participants looked towards the mirror compared to when they looked at their right hand suggesting that gaze direction reduces the typical proximo-distal biases in tactile localization. Moreover, vision of the hand modulates the internal configuration of points’ locations, by elongating it, in the radio-ulnar axis

Finger posture modulates structural body representations

Patients with lesions of the left posterior parietal cortex commonly fail in identifying their fingers, a condition known as finger agnosia, yet are relatively unimpaired in sensation and skilled action. Such dissociations have traditionally been interpreted as evidence that structural body representations (BSR), such as the body structural description, are distinct from sensorimotor representations, such as the body schema. We investigated whether performance on tasks commonly used to assess finger agnosia is modulated by changes in hand posture. We used the ‘in between’ test in which participants estimate the number of unstimulated fingers between two touched fingers or a localization task in which participants judge which two fingers were stimulated. Across blocks, the fingers were placed in three levels of splay. Judged finger numerosity was analysed, in Exp. 1 by direct report and in Exp. 2 as the actual number of fingers between the fingers named. In both experiments, judgments were greater when non-adjacent stimulated fingers were positioned far apart compared to when they were close together or touching, whereas judgements were unaltered when adjacent fingers were stimulated. This demonstrates that BSRs are not fixed, but are modulated by the real-time physical distances between body parts

The effects of instrumental action on perceptual hand maps

Perceiving the external spatial location of body parts using position sense requires that immediate proprioceptive afferent signals be integrated with information about body size and shape. Longo and Haggard (Proc Natl Acad Sci USA 107:11727–11732, 2010) developed a method to measure perceptual hand maps reflecting this metric information about body size and shape. In this paradigm, participants indicate the perceived location of landmarks on their occluded hand by pointing with a long baton held in their other hand. By comparing the relative location of judgments of different hand landmarks, perceptual hand maps can be constructed and compared to actual hand structure. The maps show large and highly stereotyped distortions. Here, I investigated the potential effect of biases related to active motor control of the hand doing the pointing in these distortions. Participants localized the fingertip and knuckle of each finger on their occluded left hand either by actively pointing with a baton held in their right hand (pointing condition) or by giving verbal commands to an experimenter on how to move the baton (verbal condition). Similar distortions were clearly apparent in both conditions, suggesting that they are not an artifact of motor control biases related to the pointing hand

Distorted body representations are robust to differences in experimental instructions

Several recent reports have shown that even healthy adults maintain highly distorted representations of the size and shape of their body. These distortions have been shown to be highly consistent across different study designs and dependent measures. However, previous studies have found that visual judgments of size can be modulated by the experimental instructions used, for example, by asking for judgments of the participant’s subjective experience of stimulus size (i.e., apparent instructions) versus judgments of actual stimulus properties (i.e., objective instructions). Previous studies investigating internal body representations have relied exclusively on ‘apparent’ instructions. Here, we investigated whether apparent versus objective instructions modulate findings of distorted body representations underlying position sense (Exp. 1), tactile distance perception (Exp. 2), as well as the conscious body image (Exp. 3). Our results replicate the characteristic distortions previously reported for each of these tasks and further show that these distortions are not affected by instruction type (i.e., apparent vs. objective). These results show that the distortions measured with these paradigms are robust to differences in instructions and do not reflect a dissociation between perception and belief

The contribution of primary and secondary somatosensory cortices to the representation of body parts and body sides: an fMRI adaptation study

Although the somatosensory homunculus is a classically used description of the way somatosensory inputs are processed in the brain, the actual contributions of primary (SI) and secondary (SII) somatosensory cortices to the spatial coding of touch remain poorly understood. We studied adaptation of the fMRI BOLD response in the somatosensory cortex by delivering pairs of vibrotactile stimuli to the finger tips of the index and middle fingers. The first stimulus (adaptor) was delivered either to the index or to the middle finger of the right or left hand, whereas the second stimulus (test) was always administered to the left index finger. The overall BOLD response evoked by the stimulation was primarily contralateral in SI and was more bilateral in SII. However, our fMRI adaptation approach also revealed that both somatosensory cortices were sensitive to ipsilateral as well as to contralateral inputs. SI and SII adapted more after subsequent stimulation of homologous as compared with nonhomologous fingers, showing a distinction between different fingers. Most importantly, for both somatosensory cortices, this finger-specific adaptation occurred irrespective of whether the tactile stimulus was delivered to the same or to different hands. This result implies integration of contralateral and ipsilateral somatosensory inputs in SI as well as in SII. Our findings suggest that SI is more than a simple relay for sensory information and that both SI and SII contribute to the spatial coding of touch by discriminating between body parts (fingers) and by integrating the somatosensory input from the two sides of the body (hands)

Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis

Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin\ub1pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3\ub16.5 vs 10.5\ub13.8, P<.0001 and 8.4\ub12.1 vs 5.7\ub11.3, P<.0001, respectively) and FCH (17.3\ub15.9 vs 10.1\ub12.8, P=.001 and 8.2\ub11.6 vs 5.5\ub11, P=.001, respectively). Short-treatment mortality was higher in patients with baseline MELD 6525 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long-term mortality was 53.3% among patients with baseline MELD 6520 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child-Turcotte-Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals-based treatments for severe post-transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long-term survival. The setting of severe HCV recurrence may require the identification of "too-sick-to-treat patients" to avoid futile treatments

Using machine learning to predict antibody response to SARS-CoV-2 vaccination in solid organ transplant recipients: the multicentre ORCHESTRA cohort

Objectives: Study aim is to assess predictors of negative antibody response (AbR) in solid organ transplant (SOT) recipients after the first booster of SARS-CoV-2 vaccination. Methods: SOT recipients receiving SARS-CoV-2 vaccination were prospectively enrolled (March 2021-January 2022) at six hospitals in Italy and Spain. AbR was assessed at first dose (t0), second dose (t1), 3±1 month (t2), and 1 month after third dose (t3). Negative AbR at t3 was defined as anti-receptor binding domain titre &lt;45 BAU/mL. Machine Learning models were developed to predict the individual risk of negative (vs. positive) AbR using as covariates age, type of transplant, time between transplant and vaccination, immunosuppressive drugs, type of vaccine, and graft function, and subsequently assessed using a validation cohort. Results: Overall, 1615 SOT recipients (1072 [66.3%] males, mean±standard deviation (SD) age 57.85±13.77) were enrolled and 1211 received three vaccination doses. Negative AbR rate decreased from (886/946) 93.66% to (202/923) 21.90% from t0 to t3. Univariate analysis showed that older patients (mean age 60.21±11.51 vs. 58.11±13.08), anti-metabolites (57.9% vs. 35.1%) steroids (52.9% vs. 38.5%), recent transplantation (&lt;3 years) (17.8% vs. 2.3%), and kidney, heart, or lung compared to liver transplantation (25%, 31.8%, 30.4% vs. 5.5%) had a higher likelihood of negative AbR. Machine learning algorithms showing best prediction performance were logistic regression (precision recall curve-PRAUC mean 0.37 [95%CI 0.36-0.39]) and k-Nearest Neighbors (PRAUC 0.36 [0.35-0.37]). Conclusions: Almost a quarter of SOT recipients showed negative AbR after first booster dosage. Unfortunately, clinical information cannot efficiently predict negative AbR even with ML algorithms