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Understanding causal relationships and violations of those relationships is fundamental to learning about the world around us. Over time some of these relationships become so firmly established that they form part of an implicit belief system about what is possible and impossible in the world. Previous studies investigating the neural correlates of violations of learned relationships have focused on relationships that were task-specific and probabilistic. In contrast, the present study uses magic-trick perception as a means of investigating violations of relationships that are long-established, deterministic, and that form part of the aforementioned belief system. Compared to situations in which expected causal relationships are observed, magic trick perception recruited dorso-lateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), brain regions associated with the detection of conflict and the implementation of cognitive control. These activations were greater in the left hemisphere, supporting a role for this hemisphere in the interpretation of complex events. DLPFC is more greatly activated by magic tricks than by surprising events, but not more greatly activated by surprising than non surprising events, suggesting that this region plays a special role in causality processing. The results suggest a role for cognitive control regions in the left hemisphere in a neurobiology of disbelief.

[...]the principle of civil society participation in law-making processes is firmly established in international law and standards, including full meaningful and effective consultation in treaty drafting processes. [...]although the pandemic treaty may only be the second treaty negotiated by WHO member states, there are decades of international practice to draw on in relation to civil society involvement in treaty drafting. World Alliance for Citizen Participation; Courtenay Howe, STOPAIDS; Tomaso Falchetta, Privacy International; Naomi Burke-Shyne, Harm Reduction International; Rossella De Falco, Global Initiative for Economic, Social and Cultural Rights; Nina Sun, Jonathan Mann Global Health and Human Rights Initiative, Drexel Dornsife School of Public Health; Joe Amon, Jonathan Mann Global Health and Human Rights Initiative, Drexel Dornsife School of Public Health; Shirin Heidari, GENDRO; Bernard Kadasia, GENDRO; Baba Aye, Public Services International; Nicoletta Dentico, Society for International Development; Ann Harrison, Amnesty International; Ruth Morgan Thomas, Global Network of Sex Work Projects (NSWP); Yassen Tcholakov, McGill University; Sara (Meg) Davis, Graduate Institute Geneva; Benjamin Mason Meier, University of North Carolina at Chapel Hill; Thomas Schwarz, Medicus Mundi International - Network Health for All; Roojin Habibi, Osgoode Hall Law School. 1 Guterres A. The world faces a pandemic of human rights abuses in the wake of Covid-19. https://www.theguardian.com/global-development/2021/feb/22/world-faces-pandemic-human-rights-abuses-covid-19-antonio-guterres 2 The Independent Panel.

Rationale Substances of misuse (such as nicotine) are associated with increases in activation within the mesocorticolimbic brain system, a system thought to mediate the rewarding effects of drugs of abuse. Pharmacological treatments have been designed to reduce cigarette cravings during temporary abstinence. Exercise has been found to be an effective tool for controlling cigarette cravings. Objective The objective of this study is to assess the effect of exercise on regional brain activation in response to smoking-related images during temporary nicotine abstinence. Method In a randomized crossover design, regular smokers ( n  = 10) undertook an exercise (10 min moderate-intensity stationary cycling) and control (passive seating for same duration) session, following 15 h of nicotine abstinence. Following treatments, participants entered a functional Magnetic Resonance Imaging (fMRI) scanner. Subjects viewed a random series of smoking and neutral images for 3 s, with an average inter-stimulus-interval (ISI) of 10 s. Self-reported cravings were assessed at baseline, mid-, and post-treatments. Results A significant interaction effect (time by group) was found, with self-reported cravings lower during and following exercise. During control scanning, significant activation was recorded in areas associated with reward (caudate nucleus), motivation (orbitofrontal cortex) and visuo-spatial attention (parietal lobe, parahippocampal, and fusiform gyrus). Post-exercise scanning showed hypo-activation in these areas with a concomitant shift of activation towards areas identified in the ‘brain default mode’ (Broadmanns Area 10). Conclusion The study confirms previous evidence that a single session of exercise can reduce cigarette cravings, and for the first time provides evidence of a shift in regional activation in response to smoking cues.

Background Natural history studies in neuromuscular disorders are vital to understand the disease evolution and to find sensitive outcome measures. We performed a longitudinal assessment of quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (31P MRS) outcome measures and evaluated their relationship with function in lower limb skeletal muscle of dysferlinopathy patients. Methods Quantitative MRI/31P MRS data were obtained at 3 T in two different sites in 54 patients and 12 controls, at baseline, and three annual follow‐up visits. Fat fraction (FF), contractile cross‐sectional area (cCSA), and muscle water T2 in both global leg and thigh segments and individual muscles and 31P MRS indices in the anterior leg compartment were assessed. Analysis included comparisons between patients and controls, assessments of annual changes using a linear mixed model, standardized response means (SRM), and correlations between MRI and 31P MRS markers and functional markers. Results Posterior muscles in thigh and leg showed the highest FF values. FF at baseline was highly heterogeneous across patients. In ambulant patients, median annual increases in global thigh and leg segment FF values were 4.1% and 3.0%, respectively (P < 0.001). After 3 years, global thigh and leg FF increases were 9.6% and 8.4%, respectively (P < 0.001). SRM values for global thigh FF were over 0.8 for all years. Vastus lateralis muscle showed the highest SRM values across all time points. cCSA decreased significantly after 3 years with median values of 11.0% and 12.8% in global thigh and global leg, respectively (P < 0.001). Water T2 values in ambulant patients were significantly increased, as compared with control values (P < 0.001). The highest water T2 values were found in the anterior part of thigh and leg. Almost all 31P MRS indices were significantly different in patients as compared with controls (P < 0.006), except for pHw, and remained, similar as to water T2, abnormal for the whole study duration. Global thigh water T2 at baseline was significantly correlated to the change in FF after 3 years (ρ = 0.52, P < 0.001). There was also a significant relationship between the change in functional score and change in FF after 3 years in ambulant patients (ρ = −0.55, P = 0.010). Conclusions This multi‐centre study has shown that quantitative MRI/31P MRS measurements in a heterogeneous group of dysferlinopathy patients can measure significant changes over the course of 3 years. These data can be used as reference values in view of future clinical trials in dysferlinopathy or comparisons with quantitative MRI/S data obtained in other limb‐girdle muscular dystrophy subtypes.

Rationale Smokers show heightened activation toward smoking-related stimuli and experience increased cravings which can precipitate smoking cessation relapse. Exercise can be effective for modulating cigarette cravings and attenuating reactivity to smoking cues, but the mechanism by which these effects occur remains uncertain. Objective The objective of the study was to assess the effect of exercise on regional brain activation in response to smoking-related images during temporary nicotine abstinence. Methods In a randomised crossover design, overnight abstinent smokers ( n  = 20) underwent an exercise (10-min moderate-intensity stationary cycling) and passive control (seating for the same duration) treatment, following 15 h of nicotine abstinence. After each treatment, participants underwent functional magnetic resonance imaging (fMRI) brain scanning while viewing a random series of blocked smoking or neutral images. Self-reported cravings were assessed at baseline, mid-, and post-treatments. Results There was a significant interaction effect (treatment × time) for desire to smoke, F (2,32) = 12.5, p  < 0.001, with significantly lower scores following the exercise at all time points compared with the control treatment. After both exercise and rest, significant areas of activation were found in areas of the limbic lobe and in areas associated with visual attention in response to smoking-related stimuli. Smokers showed increased activation to smoking images in areas associated with primary and secondary visual processing following rest, but not following a session of exercise. Conclusion The study shows differing activation towards smoking images following exercise compared to a control treatment and may point to a neuro-cognitive process following exercise that mediates effects on cigarette cravings.

Background and objectiveDysferlinopathies are a group of muscle disorders caused by mutations in the DYSF gene. Previous muscle imaging studies describe a selective pattern of muscle involvement in smaller patient cohorts, but a large imaging study across the entire spectrum of the dysferlinopathies had not been performed and previous imaging findings were not correlated with functional tests.MethodsWe present cross-sectional T1-weighted muscle MRI data from 182 patients with genetically confirmed dysferlinopathies. We have analysed the pattern of muscles involved in the disease using hierarchical analysis and presented it as heatmaps. Results of the MRI scans have been correlated with relevant functional tests for each region of the body analysed.ResultsIn 181 of the 182 patients scanned, we observed muscle pathology on T1-weighted images, with the gastrocnemius medialis and the soleus being the most commonly affected muscles. A similar pattern of involvement was identified in most patients regardless of their clinical presentation. Increased muscle pathology on MRI correlated positively with disease duration and functional impairment.ConclusionsThe information generated by this study is of high diagnostic value and important for clinical trial development. We have been able to describe a pattern that can be considered as characteristic of dysferlinopathy. We have defined the natural history of the disease from a radiological point of view. These results enabled the identification of the most relevant regions of interest for quantitative MRI in longitudinal studies, such as clinical trials.Clinical trial registrationNCT01676077.

Objectives To establish thresholds of pain and quality of life scores corresponding to patient acceptable symptom state (PASS) in patients with oral lichen planus (OLP) and to assess demographic and clinical factors associated with achieving the PASS. Methods Prospective data from baseline and 4-month follow-up including Visual Analogue Scale (VAS), Numerical Rating Scale (NRS), 14-item Oral Health Impact Profile (OHIP-14) and 15-item and 26-item Chronic Oral Mucosal Disease Questionnaire (COMDQ-15; COMDQ-26) were collected from 281 patients with OLP. An anchoring approach based upon the patient’s opinion on acceptability of OLP status was applied. Associated factors for achieving the PASS were analysed using multivariate logistic regression. Results About two-thirds (68.7%) of participants rated their OLP status as acceptable. Cut-off thresholds for PASS were as follows: ≤ 28 mm for VAS, ≤ 3 for NRS, ≤ 18 for total OHIP-14, ≤ 26 for total COMDQ-15 and ≤ 48 for total COMDQ-26. Based upon results of multivariate logistic analysis, factors associated with being in PASS were lower pain intensity, lower depressive symptoms and lower disease activity of OLP. Conclusion The present study established PASS cut-off thresholds as a tool facilitating interpretation of pain and quality of life outcomes relevant to individuals with OLP. Clinical relevance Identified PASS estimates could be utilised as clinically important endpoints in clinical practice of OLP as well as eligibility criteria for recruiting participants in clinical trials assessing effectiveness of symptomatic intervention of OLP.

Aim: The aim of this study is to analyze the brain activity patterns during the observation of painful expressions and to establish the relationship between this activity and the scores obtained on the Interpersonal Reactivity Index (IRI). Methods: The study included twenty healthy, right-handed subjects (10 women). We conducted a task-based and resting-state functional magnetic resonance imaging (fMRI) study. The task involved observing pictures displaying painful expressions. We performed a region of interest (ROI) analysis focusing on the core regions of the sensorimotor mirror neuron system (MNS). Resting-state fMRI was utilized to assess the functional connectivity of the sensorimotor MNS regions with the rest of the cortex using a seed-to-voxel approach. Additionally, we conducted a regression analysis to examine the relationship between brain activity and scores from the IRI subtests. Results: Observing painful expressions led to increased activity in specific regions of the frontal, temporal, and parietal lobes. The largest cluster of activation was observed in the left inferior parietal lobule (IPL). However, the ROI analysis did not reveal any significant activity in the remaining core regions of the sensorimotor MNS. The regression analysis demonstrated a positive correlation between brain activity during the observation of pain and the “empathic concern” subtest scores of the IRI in both the cingulate gyri and bilateral IPL. Finally, we identified a positive relationship between the “empathic concern” subtest of the IRI and the functional connectivity (FC) of bilateral IPLs with the bilateral prefrontal cortex and the right IFG. Conclusion: Observing expressions of pain triggers activation in the sensorimotor MNS, and this activation is influenced by the individual’s level of empathy.

ObjectivesTo explore potential mechanisms that underpin the cardiac abnormalities seen in chronic fatigue syndrome (CFS) using non-invasive cardiac impedance, red cell mass and plasma volume measurements.MethodsCardiac MR (MR) examinations were performed using 3 T Philips Intera Achieva scanner (Best, NL) in participants with CFS (Fukuda; n=47) and matched case-by-case controls. Total volume (TV), red cell volume (RCV) and plasma volume (PV) measurements were performed (41 CFS and 10 controls) using the indicator dilution technique using simultaneous 51-chromium labelling of red blood cells and 125-iodine labelling of serum albumin.ResultsThe CFS group length of history (mean±SD) was 14±10 years. Patients with CFS had significantly reduced end-systolic and end-diastolic volumes together with reduced end-diastolic wall masses (all p<0.0001). Mean±SD RCV was 1565±443 mL with 26/41 (63%) having values below 95% of expected. PV was 2659±529 mL with 13/41 (32%) <95% expected. There were strong positive correlations between TV, RCV and PV and cardiac end-diastolic wall mass (all p<0.0001; r2=0.5). Increasing fatigue severity correlated negatively with lower PV (p=0.04; r2=0.2). There were no relationships between any MR or volume measurements and length of history, suggesting that deconditioning was unlikely to be the cause of these abnormalities.ConclusionsThis study confirms an association between reduced cardiac volumes and blood volume in CFS. Lack of relationship between length of disease, cardiac and plasma volumes suggests findings are not secondary to deconditioning. The relationship between plasma volume and severity of fatigue symptoms suggests a potential therapeutic target in CFS.