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Contemporary models of decision-making under risk focus on estimating the final value of each alternative course of action. According to such frameworks, information that has no capacity to alter a future payoff (i.e., is “non-instrumental”) should have little effect on one’s preference for risk. Importantly, however, recent work has shown that information, despite being non-instrumental, may nevertheless exert a striking influence on behavior. Here, we tested whether the opportunity to passively observe the sequence of events following a decision could modulate risky behavior, even if that information could not possibly influence the final result. Across three experiments, 71 individuals chose to accept or reject gambles on a five-window slot machine. If a gamble was accepted, each window was sequentially revealed prior to the outcome being declared. Critically, we informed participants about which windows would subsequently provide veridical information about the gamble outcome, should that gamble be accepted. Our analyses revealed three key findings. First, the opportunity to observe the consequences of one’s choice significantly increased the likelihood of gambling, despite that information being entirely non-instrumental. Second, this effect generalized across different stakes. Finally, choices were driven predominantly by the likelihood that information could result in an earlier resolution of uncertainty. These findings demonstrate the importance of anticipatory information to decision-making under risk. More broadly, we provide strong evidence for the utility of non-instrumental information, by demonstrating its capacity to modulate primary economic decisions that should be driven by more motivationally salient variables associated with risk and reward.

•Novel methodology and software for MR-PET registration uncertainty analysis.•Registration software had the biggest effect on MR-PET registration precision, followed by reconstruction parameters (i.e., iterations, smoothing) and PET count level.•PVC can significantly improve the PET signal, but since it relies on precise MR-PET registration, it also increases PET signal variability and hence care should be taken when using it. Accurate regional brain quantitative PET measurements, particularly when using partial volume correction, rely on robust image registration between PET and MR images. We argue here that the precision, and hence the uncertainty, of MR-PET image registration is mainly driven by the registration implementation and the quality of PET images due to their lower resolution and higher noise compared to the structural MR images. We propose a dedicated uncertainty analysis for quantifying the precision of MR-PET registration, centred around the bootstrap resampling of PET list-mode events to generate multiple PET image realisations with different noise (count) levels. The effects of PET image reconstruction parameters, such as the use of attenuation and scatter corrections and different number of iterations, on the precision and accuracy of MR-PET registration were investigated. In addition, the performance of four software packages with their default settings for rigid inter-modality image registration were considered: NiftyReg, Vinci, FSL and SPM. Four distinct PET image distributions made of two early time frames (similar to cortical FDG) and two late frames using two amyloid PET dynamic acquisitions of one amyloid positive and one amyloid negative participants were investigated. For the investigated four PET frames, the biggest impact on the uncertainty was observed between registration software packages (up to 10-fold difference in precision) followed by the reconstruction parameters. On average, the lowest uncertainty for different PET frames and brain regions was observed with SPM and two iterations of fully quantitative image reconstruction. The observed uncertainty for the varying PET count-level (from 5% to 60%) was slightly lower than for the reconstruction parameters. We also observed that the registration uncertainty in quantitative PET analysis depends on amyloid status of the considered PET frames, with increased uncertainty (up to three times) when using post-reconstruction partial volume correction. This analysis is applicable for PET data obtained from either PET/MR or PET/CT scanners.

Task decisions and confidence ratings are fundamental measures in metacognition research, but using these reports requires collecting them in some order. Only three orders exist and are used in an ad hoc manner across studies. Evidence suggests that when task decisions precede confidence, this report order can enhance metacognition. If verified, this effect pervades studies of metacognition and will lead the synthesis of this literature to invalid conclusions. In this Registered Report, we tested the effect of report order across popular domains of metacognition and probed two factors that may underlie why order effects have been observed in past studies: report time and motor preparation. We examined these effects in a perception experiment ( n  = 75) and memory experiment ( n  = 50), controlling task accuracy and learning. Our registered analyses found little effect of report order on metacognitive efficiency, even when timing and motor preparation were experimentally controlled. Our findings suggest the order of task decisions and confidence ratings has little effect on metacognition, and need not constrain secondary analysis or experimental design. Decisions and confidence ratings are crucial to metacognition research. A concern is whether the order in which first and second order ratings are collected may affect results. This Registered Report finds order has little effect on metacognitive efficiency.

Objectives The objective was to examine the impact of state and trait mindfulness cultivated through body scan meditation, on bodily multisensory integration, in order to explore effects of increased non-judgmental/accepting attention to ambiguous bodily sensations. Methods Multisensory integration was operationalised through the rubber hand illusion, which was measured through subjective questionnaires, proprioceptive drift and skin conductance to perceived threat. State mindfulness was induced through a 20-min body scan meditation. Trait mindfulness was enhanced through a 14-day training programme of 10–15-min body scan meditation each day. An active control group engaged in relaxed listening. Trait mindfulness and trait bodily awareness were measured through questionnaires. Results The state mindfulness induction was associated with a stronger reported rubber hand illusion than relaxed listening. In contrast, both 14 days of mindfulness training and of relaxed listening were associated with a decrease in reported rubber hand illusion, with a larger decrease after mindfulness training compared to relaxed listening. Conclusions A state mindfulness induction increased participants’ experience of the bodily illusion, while longer-term mindfulness training dampened the illusion, suggesting state and trait mindfulness via body scan meditation may have differential relationships with bodily multisensory integration. We discuss this finding in terms of initial attention-mediated salience of ambiguous somatosensory signals, followed by acceptance.

Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [11C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb pain or Anaesthesia Dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [11C]DPN and [15O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation. The regional cerebral tracer distribution and kinetics were quantified for the whole brain and brainstem. Analysis was performed on a voxel-wise basis using statistical parametric mapping (SPM) and also within brainstem regions of interest and correlated to the DBS-induced improvement in pain score and mood. Brain-wide analysis identified a single cluster of reduced [11C]DPN binding (15.5% reduction) in the caudal, dorsal PAG following DBS from effective electrodes located in rostral dorsal/lateral PAG. There was no evidence for an accompanying focal change in blood flow within the PAG. No correlation was found between the change in PAG [11C]DPN binding and the analgesic effect or the effect on mood (POMSSV) of DBS. The analgesic effect of DBS in these subjects was not altered by systemic administration of the opioid antagonist naloxone (400ug). These findings indicate that DBS of the PAG does indeed release endogenous opioid peptides focally within the midbrain of these neuropathic pain patients but we are unable to further resolve the question of whether this release is responsible for the observed analgesic benefit. •Sequential opioid-PET imaging study of deafferentation pain patients.•All obtained analgesic benefit from deep brain stimulators (DBS) in periaqueductal grey (PAG).•PET imaging with diprenorphine showed DBS reduced binding of the radioligand in the PAG.•Change in binding consistent with DBS-evoked release of endogenous opioids.

Whether conscious perception requires attention remains a topic of intense debate. While certain complex stimuli such as faces and animals can be discriminated outside the focus of spatial attention, many simpler stimuli cannot. Because such evidence was obtained in dual-task paradigms involving no measure of subjective insight, it remains unclear whether accurate discrimination of unattended complex stimuli is the product of automatic, unconscious processing, as in blindsight, or is accessible to consciousness. Furthermore, these paradigms typically require extensive training over many hours, bringing into question whether this phenomenon can be achieved in naive subjects. We developed a novel dual-task paradigm incorporating confidence ratings to calculate metacognition and adaptive staircase procedures to reduce training. With minimal training, subjects were able to discriminate face-gender in the near absence of top–down attentional amplification, while also displaying above-chance metacognitive accuracy. By contrast, the discrimination of simple coloured discs was significantly impaired and metacognitive accuracy dropped to chance-level, even in a partial-report condition. In a final experiment, we used blended face/disc stimuli and confirmed that face-gender but not colour orientation can be discriminated in the dual task. Our results show direct evidence for metacognitive conscious access in the near absence of attention for complex, but not simple, stimuli. This article is part of the theme issue ‘Perceptual consciousness and cognitive access'.

Studies in rodent models of epilepsy suggest that multidrug efflux transporters at the blood–brain barrier, such as P-glycoprotein, might contribute to pharmacoresistance by reducing target-site concentrations of antiepileptic drugs. We assessed P-glycoprotein activity in vivo in patients with temporal lobe epilepsy. We selected 16 patients with pharmacoresistant temporal lobe epilepsy who had seizures despite treatment with at least two antiepileptic drugs, eight patients who had been seizure-free on antiepileptic drugs for at least a year after 3 or more years of active temporal lobe epilepsy, and 17 healthy controls. All participants had a baseline PET scan with the P-glycoprotein substrate (R)-[11C]verapamil. Pharmacoresistant patients and healthy controls then received a 30-min infusion of the P-glycoprotein-inhibitor tariquidar followed by another (R)-[11C]verapamil PET scan 60 min later. Seizure-free patients had a second scan on the same day, but without tariquidar infusion. Voxel-by-voxel, we calculated the (R)-[11C]verapamil plasma-to-brain transport rate constant, K1 (mL/min/cm3). Low baseline K1 and attenuated K1 increases after tariquidar correspond to high P-glycoprotein activity. Between October, 2008, and November, 2011, we completed (R)-[11C]verapamil PET studies in 14 pharmacoresistant patients, eight seizure-free patients, and 13 healthy controls. Voxel-based analysis revealed that pharmacoresistant patients had lower baseline K1, corresponding to higher baseline P-glycoprotein activity, than seizure-free patients in ipsilateral amygdala (0·031 vs 0·036 mL/min/cm3; p=0·014), bilateral parahippocampus (0·032 vs 0·037; p<0·0001), fusiform gyrus (0·036 vs 0·041; p<0·0001), inferior temporal gyrus (0·035 vs 0·041; p<0·0001), and middle temporal gyrus (0·038 vs 0·044; p<0·0001). Higher P-glycoprotein activity was associated with higher seizure frequency in whole-brain grey matter (p=0·016) and the hippocampus (p=0·029). In healthy controls, we noted a 56·8% increase of whole-brain K1 after 2 mg/kg tariquidar, and 57·9% for 3 mg/kg; in patients with pharmacoresistant temporal lobe epilepsy, whole-brain K1 increased by only 21·9% for 2 mg/kg and 42·6% after 3 mg/kg. This difference in tariquidar response was most pronounced in the sclerotic hippocampus (mean 24·5% increase in patients vs mean 65% increase in healthy controls, p<0·0001). Our results support the hypothesis that there is an association between P-glycoprotein overactivity in some regions of the brain and pharmacoresistance in temporal lobe epilepsy. If this relation is confirmed, and P-glycoprotein can be identified as a contributor to pharmacoresistance, overcoming P-glycoprotein overactivity could be investigated as a potential treatment strategy. EU-FP7 programme (EURIPIDES number 201380).

Right ventricular (RV) function is the strongest predictor of survival in pulmonary hypertension (PH) and age‐related heart disease; however, no therapies improve RV function. Understanding how the RV undoes pathological remodeling (reverse remodeling) might aid in identifying therapies, particularly in aging populations in which RV failure is significant. Our objective was to determine if the aged RV can undergo reverse remodeling following the resolution of pathological afterload by pulmonary hypertension (PH). We exposed male and female aged (18–21 months) C57BL/6 mice to hypobaric hypoxia (HH) for 4 weeks to model PH before returning the mice to normoxia for three (WK3RR) or six (WK6RR) weeks. HH stimulated RV hypertrophy and fibrosis which were attenuated with WK3RR and WK6RR. Activation of autophagy and anti‐fibrotic pathways likely underlie morphological reverse remodeling. However, HH decreased RV systolic function as assessed by fractional area change (FAC) and stroke volume (SV) that were not rescued with normoxia re‐exposure. The aged RV can undergo morphological reverse remodeling following the removal of pathological load; however, RV function does not improve. Further investigation into the mechanisms of reverse remodeling may identify potential drug therapies for maladaptive RV remodeling with aging.

Background The use of maximum standardised uptake value (SUV max ) is commonplace in oncology positron emission tomography (PET). Point spread function (PSF) modelling and time-of-flight (TOF) reconstructions have a significant impact on SUV max , presenting a challenge for centres with defined protocols for lesion classification based on SUV max thresholds. This has perhaps led to the slow adoption of these reconstructions. This work evaluated the impact of PSF and/or TOF reconstructions on SUV max , SUV peak and total lesion glycolysis (TLG) under two different schemes of post-filtering. Methods Post-filters to match voxel variance or SUV max were determined using a NEMA NU-2 phantom. Images from 68 consecutive lung cancer patients were reconstructed with the standard iterative algorithm along with TOF; PSF modelling - Siemens HD·PET (HD); and combined PSF modelling and TOF - Siemens ultraHD·PET (UHD) with the two post-filter sets. SUV max , SUV peak , TLG and signal-to-noise ratio of tumour relative to liver (SNR (T-L) ) were measured in 74 lesions for each reconstruction. Relative differences in uptake measures were calculated, and the clinical impact of any changes was assessed using published guidelines and local practice. Results When matching voxel variance, SUV max increased substantially (mean increase +32% and +49% for HD and UHD, respectively), potentially impacting outcome in the majority of patients. Increases in SUV peak were less notable (mean increase +17% and +23% for HD and UHD, respectively). Increases with TOF alone were far less for both measures. Mean changes to TLG were <10% for all algorithms for either set of post-filters. SNR (T-L) were greater than ordered subset expectation maximisation (OSEM) in all reconstructions using both post-filtering sets. Conclusions Matching image voxel variance with PSF and/or TOF reconstructions, particularly with PSF modelling and in small lesions, resulted in considerable increases in SUV max , inhibiting the use of defined protocols for lesion classification based on SUV max . However, reduced partial volume effects may increase lesion detectability. Matching SUV max in phantoms translated well to patient studies for PSF reconstruction but less well with TOF, where a small positive bias was observed in patient images. Matching SUV max significantly reduced voxel variance and potential variability of uptake measures. Finally, TLG may be less sensitive to reconstruction methods compared with either SUV max or SUV peak .