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This technical report describes a dynamic causal model of the spread of coronavirus through a population. The model is based upon ensemble or population dynamics that generate outcomes, like new cases and deaths over time. The purpose of this model is to quantify the uncertainty that attends predictions of relevant outcomes. By assuming suitable conditional dependencies, one can model the effects of interventions (e.g., social distancing) and differences among populations (e.g., herd immunity) to predict what might happen in different circumstances. Technically, this model leverages state-of-the-art variational (Bayesian) model inversion and comparison procedures, originally developed to characterise the responses of neuronal ensembles to perturbations. Here, this modelling is applied to epidemiological populations-to illustrate the kind of inferences that are supported and how the model per se can be optimised given timeseries data. Although the purpose of this paper is to describe a modelling protocol, the results illustrate some interesting perspectives on the current pandemic; for example, the nonlinear effects of herd immunity that speak to a self-organised mitigation process., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Friston KJ et al.)

Human pluripotent stem cells (PSCs) are subject to the appearance of recurrent genetic variants on prolonged culture. We have now found that, compared with isogenic differentiated cells, PSCs exhibit evidence of considerably more DNA damage during the S phase of the cell cycle, apparently as a consequence of DNA replication stress marked by slower progression of DNA replication, activation of latent origins of replication, and collapse of replication forks. As in many cancers, which, like PSCs, exhibit a shortened G1 phase and DNA replication stress, the resulting DNA damage may underlie the higher incidence of abnormal and abortive mitoses in PSCs, resulting in chromosomal non-dysjunction or cell death. However, we have found that the extent of DNA replication stress, DNA damage, and consequent aberrant mitoses can be substantially reduced by culturing PSCs in the presence of exogenous nucleosides, resulting in improved survival, clonogenicity, and population growth., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

In recent years there has been considerable research on body awareness, which is believed to arise from interoceptive and from exteroceptive signals. In addition, body awareness may be related to empathetic disposition during social interaction. In this paper we assess the psychometric properties of the Italian version of the Scale of Body Connection (SBC). We also examine SBC correlations with the Interpersonal Reactivity Index, a measure of empathy. An Italian sample (N = 576) aged from 17 to 72 years old (M = 30.43; sd 9.41) completed these surveys online. The SBC Italian translation was validated by confirmatory factor analysis showing a good model fit. The two-scale SBC factor structure was confirmed. The SBC was positively associated with the Iterpersonal Reactivity Index (IRI), demonstrating convergent validity between these two scales. Specifically SBC-Bodily Dissociation was positively correlated with IRI-Personal Distress subscale and SBC-Body Awareness was positively correlated with IRI-Emotional Concerns, -Fantasy and -Perspective Taking subscales., (Copyright © 2020. Published by Elsevier Ltd.)

We recently described a dynamic causal model of a COVID-19 outbreak within a single region. Here, we combine several of these (epidemic) models to create a (pandemic) model of viral spread among regions. Our focus is on a second wave of new cases that may result from loss of immunity-and the exchange of people between regions-and how mortality rates can be ameliorated under different strategic responses. In particular, we consider hard or soft social distancing strategies predicated on national (Federal) or regional (State) estimates of the prevalence of infection in the population. The modelling is demonstrated using timeseries of new cases and deaths from the United States to estimate the parameters of a factorial (compartmental) epidemiological model of each State and, crucially, coupling between States. Using Bayesian model reduction, we identify the effective connectivity between States that best explains the initial phases of the outbreak in the United States. Using the ensuing posterior parameter estimates, we then evaluate the likely outcomes of different policies in terms of mortality, working days lost due to lockdown and demands upon critical care. The provisional results of this modelling suggest that social distancing and loss of immunity are the two key factors that underwrite a return to endemic equilibrium., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Friston KJ et al.)

Photoelectrochemical water splitting is a promising method of clean hydrogen production for green energy uses. Here, we report on a tin-based oxide perovskite combined with an overlayer that shows enhanced bifunctional hydrogen and oxygen evolution. In our first-principles study of tin-based perovskites, based upon density functional theory, we investigate how the formation of a surface affects the electronic properties of these materials. We show that the best candidate, SrSnO 3 , possesses hydrogen and oxygen overpotentials of 0.75 and 0.72 eV, respectively, which are reduced to 0.35 and 0.54 eV with the inclusion of a ZrO 2 overlayer. Furthermore, this overlayer promotes charge extraction, stabilizes the reaction pathways, and improves the band gap such that it straddles the overpotentials between pH 0 and pH 12. This result indicates that SrSnO 3 with a ZrO 2 overlayer has significant potential as a highly efficient bifunctional water splitter for producing hydrogen and oxygen gas on the same surface.

A key challenge during the transition from laboratory/small batch to continuous manufacturing is the development of a process strategy that can easily be adopted for a larger batch/continuous process. Industrial practice is to develop the isolation strategy for a new drug/process in batch using the design of experiment (DoE) approach to determine the best isolation conditions and then transfer the isolation parameters selected to a large batch equipment/continuous isolation process. This stage requires a series of extra investigations to evaluate the effect of different equipment geometry or even the adaptation of the parameters selected to a different isolation mechanism (e.g., from dead end to cross flow filtration) with a consequent increase of R&D cost and time along with an increase in material consumption. The CFD25 is an isolation device used in the first instance to develop an isolation strategy in batch (optimization mode) using a screening DoE approach and to then verify the transferability of the strategy to a semicontinuous process (production mode). A d-optimal screening DoE was used to determine the effect of varying the input slurry. Properties such as solid loading, particle size distribution, and crystallization solvent were investigated to determine their impact on the filtration and washing performance and the characteristics of the dry isolated product. A series of crystallization (ethanol, isopropanol, and 3-methylbutan-1-ol) and wash solvents ( n -heptane, isopropyl acetate and n -dodcane) were used for the process. To mimic a real isolation process, paracetamol-related impurities, acetanilide and metacetamol, were dissolved in the mother liquor. The selected batch isolation strategy was used for the semicontinuous isolation run. Throughput and filtration parameters, such as cake resistance and flow rate, cake residual liquid content and composition, cake purity, particle-particle aggregation, and extent and strength of agglomerates, were measured to evaluate the consistency of the isolated product produced during a continuous experiment and compared with the isolated product properties obtained during the batch process development. Overall, the CFD25 is a versatile tool which allows both new chemical entity process development in batch and the production of the active pharmaceutical ingredient in semicontinuous mode using the same process parameters without changing equipment. The isolated product properties gained during the semicontinuous run are overall comparable between samples. The residual solvent content and composition differs between some samples due to filter plate blockage. In general, the mean properties obtained during semicontinuous running are comparable with the product properties simulated using the DoE., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Deaf late signers provide a unique perspective on the impact of impoverished early language exposure on the neurobiology of language: insights that cannot be gained from research with hearing people alone. Here we contrast the effect of age of sign language acquisition in hearing and congenitally deaf adults to examine the potential impact of impoverished early language exposure on the neural systems supporting a language learnt later in life. We collected fMRI data from deaf and hearing proficient users (N ​= ​52) of British Sign Language (BSL), who learnt BSL either early (native) or late (after the age of 15 years) whilst they watched BSL sentences or strings of meaningless nonsense signs. There was a main effect of age of sign language acquisition (late ​> ​early) across deaf and hearing signers in the occipital segment of the left intraparietal sulcus. This finding suggests that late learners of sign language may rely on visual processing more than early learners, when processing both linguistic and nonsense sign input - regardless of hearing status. Region-of-interest analyses in the posterior superior temporal cortices (STC) showed an effect of age of sign language acquisition that was specific to deaf signers. In the left posterior STC, activation in response to signed sentences was greater in deaf early signers than deaf late signers. Importantly, responses in the left posterior STC in hearing early and late signers did not differ, and were similar to those observed in deaf early signers. These data lend further support to the argument that robust early language experience, whether signed or spoken, is necessary for left posterior STC to show a 'native-like' response to a later learnt language., Competing Interests: Declaration of competing interest None., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to pilot-test a mind-body intervention called Mindful Awareness in Body-oriented Therapy (MABT) as an adjunct to buprenorphine for individuals with opioid use disorder (OUD). MABT, a manualized 8 week protocol, teaches interoceptive awareness skills to promote self-care and emotion regulation. A small study was designed to assess MABT recruitment and retention feasibility, and intervention acceptability, among this population. Individuals were recruited from two office-based programs providing buprenorphine treatment within a large urban community medical center. Participants were randomized to receive either treatment as usual (TAU), or TAU plus MABT. Assessments administered at baseline and 10-week follow-up included validated self-report health questionnaires and a process measure, the Multidimensional Assessment of Interoceptive Awareness, to examine interoceptive awareness skills. An additional survey and exit interview for those in the MABT study arm were administered to assess intervention satisfaction. Results showed the ability to recruit and enroll 10 participants within two-weeks, and no loss to follow-up. The MABT study group showed an increase in interoceptive awareness skills from baseline to follow-up, whereas the control group did not. Responses to the satisfaction questionnaire and exit interview were positive, indicating skills learned, satisfaction with the interventionists, and overall perceived benefit of the intervention. In summary, study results demonstrated recruitment and retention feasibility, and high intervention acceptability. This pilot study suggests preliminary feasibility of successfully implementing a larger study of MABT as an adjunct to office-based medication treatment for opioid use disorder., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Colossal permittivity materials exhibit extreme polarization in an applied electric field, providing applications in electronics and energy transmission. Understanding the atomic-scale mechanism behind colossal permittivity remains a challenging task and is key to optimizing materials with this property. The fundamental mechanism of colossal permittivity is reported and, using CaCu 3 Ti 4 O 12 as an example, it is attributed to the formation of an unusual metallic interface between the grain and grain boundary materials (CaCu 3 Ti 4 O 12 and Cu x O (x = 1, 2), respectively), not created by oxygen vacancies as is normally the case in oxide materials. This metallic layer around the grain forms confined shells of charge that pool on one side when under an applied field, which results in colossal permittivity. A route towards enhancing colossal permittivity is explained by means of manipulating the interface properties, as well as altering sample geometries. A methodology to artificially engineer colossal permittivity metamaterials is also shown., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This fMRI study of 24 healthy human participants investigated whether any part of the auditory cortex was more responsive to self-generated speech sounds compared to hearing another person speak. The results demonstrate a double dissociation in two different parts of the auditory cortex. In the right posterior superior temporal sulcus (RpSTS), activation was higher during speech production than listening to auditory stimuli, whereas in bilateral superior temporal gyri (STG), activation was higher for listening to auditory stimuli than during speech production. In the second part of the study, we investigated the function of the identified regions, by examining how activation changed across a range of listening and speech production tasks that systematically varied the demands on acoustic, semantic, phonological and orthographic processing. In RpSTS, activation during auditory conditions was higher in the absence of semantic cues, plausibly indicating increased attention to the spectral-temporal features of auditory inputs. In addition, RpSTS responded in the absence of any auditory inputs when participants were making one-back matching decisions on visually presented pseudowords. After analysing the influence of visual, phonological, semantic and orthographic processing, we propose that RpSTS (i) contributes to short term memory of speech sounds as well as (ii) spectral-temporal processing of auditory input and (iii) may play a role in integrating auditory expectations with auditory input. In contrast, activation in bilateral STG was sensitive to acoustic input and did not respond in the absence of auditory input. The special role of RpSTS during speech production therefore merits further investigation if we are to fully understand the neural mechanisms supporting speech production during speech acquisition, adult life, hearing loss and after brain injury., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Conceptual knowledge is fundamental to human cognition. Yet, the extent to which it is influenced by language is unclear. Studies of semantic processing show that similar neural patterns are evoked by the same concepts presented in different modalities (e.g., spoken words and pictures or text) [1-3]. This suggests that conceptual representations are "modality independent." However, an alternative possibility is that the similarity reflects retrieval of common spoken language representations. Indeed, in hearing spoken language users, text and spoken language are co-dependent [4, 5], and pictures are encoded via visual and verbal routes [6]. A parallel approach investigating semantic cognition shows that bilinguals activate similar patterns for the same words in their different languages [7, 8]. This suggests that conceptual representations are "language independent." However, this has only been tested in spoken language bilinguals. If different languages evoke different conceptual representations, this should be most apparent comparing languages that differ greatly in structure. Hearing people with signing deaf parents are bilingual in sign and speech: languages conveyed in different modalities. Here, we test the influence of modality and bilingualism on conceptual representation by comparing semantic representations elicited by spoken British English and British Sign Language in hearing early, sign-speech bilinguals. We show that representations of semantic categories are shared for sign and speech, but not for individual spoken words and signs. This provides evidence for partially shared representations for sign and speech and shows that language acts as a subtle filter through which we understand and interact with the world., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This paper provides a worked example of using Dynamic Causal Modelling (DCM) and Parametric Empirical Bayes (PEB) to characterise inter-subject variability in neural circuitry (effective connectivity). It steps through an analysis in detail and provides a tutorial style explanation of the underlying theory and assumptions (i.e, priors). The analysis procedure involves specifying a hierarchical model with two or more levels. At the first level, state space models (DCMs) are used to infer the effective connectivity that best explains a subject's neuroimaging timeseries (e.g. fMRI, MEG, EEG). Subject-specific connectivity parameters are then taken to the group level, where they are modelled using a General Linear Model (GLM) that partitions between-subject variability into designed effects and additive random effects. The ensuing (Bayesian) hierarchical model conveys both the estimated connection strengths and their uncertainty (i.e., posterior covariance) from the subject to the group level; enabling hypotheses to be tested about the commonalities and differences across subjects. This approach can also finesse parameter estimation at the subject level, by using the group-level parameters as empirical priors. The preliminary first level (subject specific) DCM for fMRI analysis is covered in a companion paper. Here, we detail group-level analysis procedures that are suitable for use with data from any neuroimaging modality. This paper is accompanied by an example dataset, together with step-by-step instructions demonstrating how to reproduce the analyses., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Dynamic Causal Modelling (DCM) is the predominant method for inferring effective connectivity from neuroimaging data. In the 15 years since its introduction, the neural models and statistical routines in DCM have developed in parallel, driven by the needs of researchers in cognitive and clinical neuroscience. In this guide, we step through an exemplar fMRI analysis in detail, reviewing the current implementation of DCM and demonstrating recent developments in group-level connectivity analysis. In the appendices, we detail the theory underlying DCM and the assumptions (i.e., priors) in the models. In the first part of the guide (current paper), we focus on issues specific to DCM for fMRI. This is accompanied by all the necessary data and instructions to reproduce the analyses using the SPM software. In the second part (in a companion paper), we move from subject-level to group-level modelling using the Parametric Empirical Bayes framework, and illustrate how to test for commonalities and differences in effective connectivity across subjects, based on imaging data from any modality., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

During word and object recognition, extensive activation has consistently been observed in the left ventral occipito-temporal cortex (vOT), focused around the occipito-temporal sulcus (OTs). Previous studies have shown that there is a hierarchy of responses from posterior to anterior vOT regions (along the y-axis) that corresponds with increasing levels of recognition - from perceptual to semantic processing, respectively. In contrast, the functional differences between superior and inferior vOT responses (i.e. along the z-axis) have not yet been elucidated. To investigate, we conducted an extensive review of the literature and found that peak activation for reading varies by more than 1 cm in the z-axis. In addition, we investigated functional differences between superior and inferior parts of left vOT by analysing functional MRI data from 58 neurologically normal skilled readers performing 8 different visual processing tasks. We found that group activation in superior vOT was significantly more sensitive than inferior vOT to the type of task, with more superior vOT activation when participants were matching visual stimuli for their semantic or perceptual content than producing speech to the same stimuli. This functional difference along the z-axis was compared to existing boundaries between cytoarchitectonic areas around the OTs. In addition, using dynamic causal modelling, we show that connectivity from superior vOT to anterior vOT increased with semantic content during matching tasks but not during speaking tasks whereas connectivity from inferior vOT to anterior vOT was sensitive to semantic content for matching and speaking tasks. The finding of a functional dissociation between superior and inferior parts of vOT has implications for predicting deficits and response to rehabilitation for patients with partial damage to vOT following stroke or neurosurgery., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Training in interoceptive awareness is a promising behavioral approach for improving substance use disorder (SUD) treatment. This study examined the longitudinal effects of Mindful Awareness in Body-oriented Therapy (MABT) as an adjunct to women's SUD treatment. MABT teaches interoceptive awareness skills to promote self-care and emotion regulation., Methods: Women in intensive outpatient treatment for SUD at three community clinics were recruited and randomly assigned to one of three study conditions Treatment as Usual (TAU) + MABT, TAU + Women's Health Education (WHE), and TAU only. Four assessments were delivered over one year (N = 187) baseline, 3, 6 and 12 months to examine primary outcome of percent days abstinent from substance use, and secondary outcomes of emotion dysregulation, craving, psychological distress, mindfulness and interoceptive awareness. Changes in outcomes across time were assessed using multilevel mixed effects linear regression., Results: Substance use improved significantly for MABT vs. TAU at 6 months and 12 months. Positive longitudinal effects on secondary outcomes for MABT were evident on respiratory sinus arrhythmia (RSA), a physiological index of emotion regulation; on craving; and on interoceptive awareness skills. Analyses based on participants who completed >75% of the intervention sessions revealed additional immediate significant improvements for MABT vs. TAU and WHE on depressive symptoms and emotion regulation difficulties and longitudinal improvement on mindfulness skills., Conclusions: Results show MABT to be efficacious for longitudinal health outcomes to support women's recovery as an adjunct to community-based SUD treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We evaluated whether task-related fMRI (functional magnetic resonance imaging) BOLD (blood oxygenation level dependent) activation could be acquired under conventional anaesthesia at a depth enabling neurosurgery in five patients with supratentorial gliomas. Within a 1.5 T MRI operating room immediately prior to neurosurgery, a passive finger flexion sensorimotor paradigm was performed on each hand with the patients awake, and then immediately after the induction and maintenance of combined sevoflurane and propofol general anaesthesia. The depth of surgical anaesthesia was measured and confirmed with an EEG-derived technique, the Bispectral Index (BIS). The magnitude of the task-related BOLD response and BOLD sensitivity under anaesthesia were determined. The fMRI data were assessed by three fMRI expert observers who rated each activation map for somatotopy and usefulness for radiological neurosurgical guidance. The mean magnitudes of the task-related BOLD response under a BIS measured depth of surgical general anaesthesia were 25% (tumour affected hemisphere) and 22% (tumour free hemisphere) of the respective awake values. BOLD sensitivity under anaesthesia ranged from 7% to 83% compared to the awake state. Despite these reductions, somatotopic BOLD activation was observed in the sensorimotor cortex in all ten data acquisitions surpassing statistical thresholds of at least p < 0.001 uncorr . All ten fMRI activation datasets were scored to be useful for radiological neurosurgical guidance. Passive task-related sensorimotor fMRI acquired in neurosurgical patients under multi-pharmacological general anaesthesia is reproducible and yields clinically useful activation maps. These results demonstrate the feasibility of the technique and its potential value if applied intra-operatively. Additionally these methods may enable fMRI investigations in patients unable to perform or lie still for awake paradigms, such as young children, claustrophobic patients and those with movement disorders., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Foraging mammalian predators face a myriad of odors from potential prey. To be efficient, they must focus on rewarding odors while ignoring consistently unrewarding ones. This may be exploited as a nonlethal conservation tool if predators can be deceived into ignoring odors of vulnerable secondary prey. To explore critical design components and assess the potential gains to prey survival of this technique, we created an individual-based model that simulated the hunting behavior of three introduced mammalian predators on one of their secondary prey (a migratory shorebird) in the South Island of New Zealand. Within this model, we heuristically assessed the outcome of habituating the predators to human-deployed unrewarding bird odors before the bird's arrival at their breeding grounds, i.e., the predators were "primed." Using known home range sizes and probabilities of predators interacting with food lures, our model suggests that wide-ranging predators should encounter a relatively large number of odor points (between 10 and 115) during 27 d of priming when odor is deployed within high-resolution grids (100-150 m). Using this information, we then modeled the effect of different habituation curves (exponential and sigmoidal) on the probability of predators depredating shorebird nests. Our results show that important gains in nest survival can be achieved regardless of the shape of the habituation curve, but particularly if predators are fast olfactory learners (exponential curve), and even if some level of dishabituation occurs after prey become available. Predictions from our model can inform the amount and pattern in which olfactory stimuli need to be deployed in the field to optimize encounters by predators, and the relative gains that can be expected from reduced predation pressure on secondary prey under different scenarios of predator learning. Habituating predators to odors of threatened secondary prey may have particular efficacy as a conservation tool in areas where lethal predator control is not possible or ethical, or where even low predator densities can be detrimental to prey survival. Our approach is also relevant for determining interaction probabilities for devices other than odor points, such as bait stations and camera traps., (© 2018 by the Ecological Society of America.)

The lack of a commercial laboratory, pilot and small manufacturing scale dead end continuous filtration and drying unit it is a significant gap in the development of continuous pharmaceutical manufacturing processes for new active pharmaceutical ingredients (APIs). To move small-scale pharmaceutical isolation forward from traditional batch Nutsche filtration to continuous processing a continuous filter dryer prototype unit (CFD20) was developed in collaboration with Alconbury Weston Ltd. The performance of the prototype was evaluated by comparison with manual best practice exemplified using a modified Biotage VacMaster unit to gather data and process understanding for API filtration and washing. The ultimate objective was to link the chemical and physical attributes of an API slurry with equipment and processing parameters to improve API isolation processes. Filtration performance was characterized by assessing filtrate flow rate by application of Darcy's law, the impact on product crystal size distribution and product purity were investigated using classical analytical methods. The overall performance of the 2 units was similar, showing that the prototype CFD20 can match best manual lab practice for filtration and washing while allowing continuous processing and real-time data logging. This result is encouraging and the data gathered provides further insight to inform the development of CFD20., (Copyright © 2019 American Pharmacists Association®. All rights reserved.)

Around a third of stroke survivors suffer from acquired language disorders (aphasia), but current medicine cannot predict whether or when they might recover. Prognostic research in this area increasingly draws on datasets associating structural brain imaging data with outcome scores for ever-larger samples of stroke patients. The aim is to learn brain-behaviour trends from these data, and generalize those trends to predict outcomes for new patients. The practical significance of this work depends on the expected breadth of that generalization. Here, we show that these models can generalize across countries and native languages (from British patients tested in English to Chilean patients tested in Spanish), across neuroimaging technology (from MRI to CT), and from scans collected months or years after stroke for research purposes, to scans collected days or weeks after stroke for clinical purposes. Our results suggest one important confound, in attempting to generalize from research data to clinical data, is the delay between scan acquisition and language assessment. This delay is typically small for research data, where scans and assessments are often acquired contemporaneously. But the most natural, clinical application of these predictions will employ acute prognostic factors to predict much longer-term outcomes. We mitigated this confound by projecting the clinical patients' lesions from the time when their scans were acquired, to the time when their language abilities were assessed; with this projection in place, there was strong evidence that prognoses derived from research data generalized equally well to research and clinical data. These results encourage attention to the confounding role that lesion growth may play in other types of lesion-symptom analysis., (Copyright © 2019. Published by Elsevier Inc.)

Background: Emotion regulation is increasingly recognized as important for the prevention and treatment of substance use disorder (SUD). However, there is an identified lack of physiological indexes of emotion dysregulation in SUD treatment studies, critically needed to better understand the link between emotion regulation capacity (measured physiologically) and self-report health outcomes among individuals in SUD treatment., Objective: To examine the association between respiratory sinus arrhythmia (RSA) and self-report health outcomes among women in SUD treatment., Methods: This is a cross-sectional study based on baseline data from 217 women enrolled in a randomized control trial to study a mind-body intervention as an adjunct to SUD treatment. All participants were enrolled in community-based outpatient treatment. Participants were administered questionnaires to examine sample characteristics, mental health symptoms, and interoceptive awareness and mindfulness skills. RSA data was gathered as an index of emotion dysregulation. Descriptive statistics, bivariate correlations, and regression were used in the analyses., Results: Findings highlight the extensive trauma histories, low SES, and the high symptoms of distress in this sample. RSA was only significantly correlated with interoceptive awareness after controlling for age and BMI. Measures of symptomatic distress and mindfulness were not correlated with RSA. Conclusions/Importance: Results provide the first evidence of RSA as an index of interoceptive awareness in this population. The inclusion of biomarkers such as RSA in SUD clinical studies may help identify individuals that are in need of targeted treatments that include interoceptive awareness training focused on improving emotion regulation.

Identity distress occurs within a variety of psychiatric conditions. Reliable tools for assessing identity-related functioning among clinical populations are greatly needed. The Self- Concept and Identity Measure (SCIM) is a brief self-report scale designed to assess healthy and disturbed identity dimensions. This measure has been validated within normative but not treatment seeking samples. The present study used an a priori confirmatory approach to replicate the SCIM's factor structure among disadvantaged women enrolled in treatment for chemical dependence ( N = 216). The original three-factor structure and item loadings generally replicated within this diagnostically diverse, significantly impaired sample. Higher SCIM scores were also associated with other problems, such as emotion dysregulation and depression. Results support the SCIM's use and scoring with clinical populations., Competing Interests: Conflict of Interest: None

Background: Sensory information gained through interoceptive awareness may play an important role in affective behavior and successful inhibition of drug use. This study examined the immediate pre-post effects of the mind-body intervention Mindful Awareness in Body-oriented Therapy (MABT) as an adjunct to women's substance use disorder (SUD) treatment. MABT teaches interoceptive awareness skills to promote self-care and emotion regulation. Methods: Women in intensive outpatient treatment (IOP) for chemical dependency ( N  = 217) at 3 community clinics in the Pacific Northwest of the United States were recruited and randomly assigned to one of 3 study conditions: MABT + treatment as usual (TAU), women's health education (WHE) +TAU (active control condition), and TAU only. At baseline and 3 months post-intervention, assessments were made of interoceptive awareness skills and mindfulness, emotion regulation (self-report and psychophysiological measures), symptomatic distress (depression and trauma-related symptoms), and substance use (days abstinent) and craving. Changes in outcomes across time were assessed using multilevel mixed-effects linear regression. Results: Findings based on an intent-to-treat approach demonstrated significant improvements in interoceptive awareness and mindfulness skills, emotion dysregulation (self-report and psychophysiology), and days abstinent for women who received MABT compared with the other study groups. Additional analyses based on participants who completed the major components of MABT (at least 75% of the intervention sessions) revealed these same improvements as well as reductions in depressive symptoms and substance craving. Conclusions: Findings that interoceptive training is associated with health outcomes for women in SUD treatment are consistent with emerging neurocognitive models that link interoception to emotion regulation and to related health outcomes, providing knowledge critical to supporting and improving SUD treatment.

The proportional recovery rule asserts that most stroke survivors recover a fixed proportion of lost function. To the extent that this is true, recovery from stroke can be predicted accurately from baseline measures of acute post-stroke impairment alone. Reports that baseline scores explain more than 80%, and sometimes more than 90%, of the variance in the patients' recoveries, are rapidly accumulating. Here, we show that these headline effect sizes are likely inflated. The key effects in this literature are typically expressed as, or reducible to, correlation coefficients between baseline scores and recovery (outcome scores minus baseline scores). Using formal analyses and simulations, we show that these correlations will be extreme when outcomes are significantly less variable than baselines, which they often will be in practice regardless of the real relationship between outcomes and baselines. We show that these effect sizes are likely to be over-optimistic in every empirical study that we found that reported enough information for us to make the judgement, and argue that the same is likely to be true in other studies as well. The implication is that recovery after stroke may not be as proportional as recent studies suggest.

Acquired language disorders after stroke are strongly associated with left hemisphere damage. When language difficulties are observed in the context of right hemisphere strokes, patients are usually considered to have atypical functional anatomy. By systematically integrating behavioural and lesion data from brain damaged patients with functional MRI data from neurologically normal participants, we investigated when and why right hemisphere strokes cause language disorders. Experiment 1 studied right-handed patients with unilateral strokes that damaged the right (n = 109) or left (n = 369) hemispheres. The most frequently impaired language task was: auditory sentence-to-picture matching after right hemisphere strokes; and spoken picture description after left hemisphere strokes. For those with auditory sentence-to-picture matching impairments after right hemisphere strokes, the majority (n = 9) had normal performance on tests of perceptual (visual or auditory) and linguistic (semantic, phonological or syntactic) processing. Experiment 2 found that these nine patients had significantly more damage to dorsal parts of the superior longitudinal fasciculus and the right inferior frontal sulcus compared to 75 other patients who also had right hemisphere strokes but were not impaired on the auditory sentence-to-picture matching task. Damage to these right hemisphere regions caused long-term speech comprehension difficulties in 67% of patients. Experiments 3 and 4 used functional MRI in two groups of 25 neurologically normal individuals to show that within the regions identified by Experiment 2, the right inferior frontal sulcus was normally activated by (i) auditory sentence-to-picture matching; and (ii) one-back matching when the demands on linguistic and non-linguistic working memory were high. Together, these experiments demonstrate that the right inferior frontal cortex contributes to linguistic and non-linguistic working memory capacity (executive function) that is needed for normal speech comprehension. Our results link previously unrelated literatures on the role of the right inferior frontal cortex in executive processing and the role of executive processing in sentence comprehension; which in turn helps to explain why right inferior frontal activity has previously been reported to increase during recovery of language function after left hemisphere stroke. The clinical relevance of our findings is that the detrimental effect of right hemisphere strokes on language is (i) much greater than expected; (ii) frequently observed after damage to the right inferior frontal sulcus; (iii) task dependent; (iv) different to the type of impairments observed after left hemisphere strokes; and (v) can result in long-lasting deficits that are (vi) not the consequence of atypical language lateralization.

This paper provides a historical and future perspective on how neuropsychology and neuroimaging can be used to develop cognitive models of human brain functions. Section 1 focuses on the emergence of cognitive modelling from neuropsychology, why lesion location was considered to be unimportant and the challenges faced when mapping symptoms to impaired cognitive processes. Section 2 describes how established cognitive models based on behavioural data alone cannot explain the complex patterns of distributed brain activity that are observed in functional neuroimaging studies. This has led to proposals for new cognitive processes, new cognitive strategies and new functional ontologies for cognition. Section 3 considers how the integration of data from lesion, behavioural and functional neuroimaging studies of large cohorts of brain damaged patients can be used to determine whether inter-patient variability in behaviour is due to differences in the premorbid function of each brain region, lesion site or cognitive strategy. This combination of neuroimaging and neuropsychology is providing a deeper understanding of how cognitive functions can be lost and re-learnt after brain damage - an understanding that will transform our ability to generate and validate cognitive models that are both physiologically plausible and clinically useful., (Copyright © 2017. Published by Elsevier Ltd.)

This study investigated how sample size affects the reproducibility of findings from univariate voxel-based lesion-deficit analyses (e.g., voxel-based lesion-symptom mapping and voxel-based morphometry). Our effect of interest was the strength of the mapping between brain damage and speech articulation difficulties, as measured in terms of the proportion of variance explained. First, we identified a region of interest by searching on a voxel-by-voxel basis for brain areas where greater lesion load was associated with poorer speech articulation using a large sample of 360 right-handed English-speaking stroke survivors. We then randomly drew thousands of bootstrap samples from this data set that included either 30, 60, 90, 120, 180, or 360 patients. For each resample, we recorded effect size estimates and p values after conducting exactly the same lesion-deficit analysis within the previously identified region of interest and holding all procedures constant. The results show (1) how often small effect sizes in a heterogeneous population fail to be detected; (2) how effect size and its statistical significance varies with sample size; (3) how low-powered studies (due to small sample sizes) can greatly over-estimate as well as under-estimate effect sizes; and (4) how large sample sizes (N ≥ 90) can yield highly significant p values even when effect sizes are so small that they become trivial in practical terms. The implications of these findings for interpreting the results from univariate voxel-based lesion-deficit analyses are discussed., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In this study, we hypothesized that if the same deficit can be caused by damage to one or another part of a distributed neural system, then voxel-based analyses might miss critical lesion sites because preservation of each site will not be consistently associated with preserved function. The first part of our investigation used voxel-based multiple regression analyses of data from 359 right-handed stroke survivors to identify brain regions where lesion load is associated with picture naming abilities after factoring out variance related to object recognition, semantics and speech articulation so as to focus on deficits arising at the word retrieval level. A highly significant lesion-deficit relationship was identified in left temporal and frontal/premotor regions. Post-hoc analyses showed that damage to either of these sites caused the deficit of interest in less than half the affected patients (76/162 = 47%). After excluding all patients with damage to one or both of the identified regions, our second analysis revealed a new region, in the anterior part of the left putamen, which had not been previously detected because many patients had the deficit of interest after temporal or frontal damage that preserved the left putamen. The results illustrate how (i) false negative results arise when the same deficit can be caused by different lesion sites; (ii) some of the missed effects can be unveiled by adopting an iterative approach that systematically excludes patients with lesions to the areas identified in previous analyses, (iii) statistically significant voxel-based lesion-deficit mappings can be driven by a subset of patients; (iv) focal lesions to the identified regions are needed to determine whether the deficit of interest is the consequence of focal damage or much more extensive damage that includes the identified region; and, finally, (v) univariate voxel-based lesion-deficit mappings cannot, in isolation, be used to predict outcome in other patients., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We consider between-subject variance in brain function as data rather than noise. We describe variability as a natural output of a noisy plastic system (the brain) where each subject embodies a particular parameterisation of that system. In this context, variability becomes an opportunity to: (i) better characterise typical versus atypical brain functions; (ii) reveal the different cognitive strategies and processing networks that can sustain similar tasks; and (iii) predict recovery capacity after brain damage by taking into account both damaged and spared processing pathways. This has many ramifications for understanding individual learning preferences and explaining the wide differences in human abilities and disabilities. Understanding variability boosts the translational potential of neuroimaging findings, in particular in clinical and educational neuroscience., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Emotion regulation involves a coherent relationship with the self, specifically effective communication between body, mind, and feelings. Effective emotion regulation involves the ability to accurately detect and evaluate cues related to physiological reactions to stressful events, accompanied by appropriate regulation strategies that temper and influence the emotional response. There is compelling evidence demonstrating links between poor or disrupted awareness of sensory information, or interoceptive awareness, and difficulties with emotion regulation. This paper presents a framework, based on psychological and neurobiological research, for understanding how interoceptive awareness facilitates regulation and an integrated sense of self, and thus contributes to health and well-being. A mind-body therapeutic approach called mindful awareness in body-oriented therapy (MABT), uniquely designed to teach fundamental skills of interoceptive awareness, is described. MABT develops the distinct interoceptive awareness capacities of identifying, accessing, and appraising internal bodily signals that are identified in physiological models as the critical components of interoception for emotion regulation. The explanatory model is that the development of these key interoceptive capacities improves sensory (physical and emotional) awareness, reduces distress, and improves regulation. Strategies for teaching and learning interoceptive awareness are not well-developed in mindfulness or psychotherapeutic approaches, particularly important for people who may have difficulty attending to interoceptive awareness due to stress, chronic pain or trauma. To address this issue, MABT provides an individualized protocol for scaffolding interoceptive awareness through a combination of psychoeducation and somatic approaches explicitly addressing difficulties with interoceptive processing. Clinical vignettes are included to provide exemplars of this approach and to highlight key components of the therapeutic process. Results from research are also included to highlight the acceptability, safety, health outcomes, and possible mechanisms underlying the MABT approach.

This study investigated whether brain activity in Dutch-French bilinguals during semantic access to concepts from one language could be used to predict neural activation during access to the same concepts from another language, in different language modalities/tasks. This was tested using multi-voxel pattern analysis (MVPA), within and across language comprehension (word listening and word reading) and production (picture naming). It was possible to identify the picture or word named, read or heard in one language (e.g. maan, meaning moon) based on the brain activity in a distributed bilateral brain network while, respectively, naming, reading or listening to the picture or word in the other language (e.g. lune). The brain regions identified differed across tasks. During picture naming, brain activation in the occipital and temporal regions allowed concepts to be predicted across languages. During word listening and word reading, across-language predictions were observed in the rolandic operculum and several motor-related areas (pre- and postcentral, the cerebellum). In addition, across-language predictions during reading were identified in regions typically associated with semantic processing (left inferior frontal, middle temporal cortex, right cerebellum and precuneus) and visual processing (inferior and middle occipital regions and calcarine sulcus). Furthermore, across modalities and languages, the left lingual gyrus showed semantic overlap across production and word reading. These findings support the idea of at least partially language- and modality-independent semantic neural representations., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Elastin-like proteins (ELPs) are known to undergo liquid-liquid phase separation reversibly above a concentration-dependent transition temperature. Previous studies suggested that, as temperature increases, ELPs experience an increased propensity for type II β-turns. However, how the ELPs behave below the phase transition temperature itself is still elusive. Here, we investigate the importance of β-turn formation during the early stages of ELP self-association. We examined the behavior of two ELPs, a 150-repeat construct that had been investigated previously (ELP[V 5 G 3 A 2 -150] as well as a new 40-repeat construct (ELP40) suitable for nuclear magnetic resonance measurements. Structural analysis of ELP40 reveals a disordered conformation, and chemical shifts throughout the sequence are insensitive to changes in temperature over 20°C. However, a low population of β-turn conformation cannot be ruled out based on chemical shifts alone. To examine the structural consequences of β-turns in ELPs, a series of structural ensembles of ELP[V 5 G 3 A 2 -150] were generated, incorporating differing amounts of β-turn bias throughout the chain. To mimic the early stages of the phase change, two monomers were paired, assuming preferential interaction at β-turn regions. This approach was justified by the observation that buried hydrophobic turns are commonly observed to interact in the Protein Data Bank. After dimerization, the ensemble-averaged hydrodynamic properties were calculated for each degree of β-turn bias, and the results were compared with analytical ultracentrifugation experiments at various temperatures. We find that the temperature dependence of the sedimentation coefficient (s 20,w o ) can be reproduced by increasing the β-turn content in the structural ensemble. This analysis allows us to estimate the presence of β-turns and weak associations under experimental conditions. Because disordered proteins frequently exhibit weak biases in secondary structure propensity, these experimentally-driven ensemble calculations may complement existing methods for modeling disordered proteins generally., (Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

For many years, researchers have sought to understand whether and when stroke survivors with acquired language impairment (aphasia) will recover. There is broad agreement that lesion location information should play some role in these predictions, but still no consensus on the best or right way to encode that information. Here, we address the emerging emphasis on the structural connectome in this work - specifically the claim that disrupted white matter connectivity conveys important, unique prognostic information for stroke survivors with aphasia. Our sample included 818 stroke patients extracted from the PLORAS database, which associates structural MRI from stroke patients with language assessment scores from the Comprehensive Aphasia Test (CAT) and basic demographic. Patients were excluded when their lesions were too diffuse or small (<1 cm3) to be detected by the Automatic Lesion Identification toolbox, which we used to encode patients' lesions as binary lesion images in standard space. Lesions were encoded using the 116 regions defined by the Automatic Anatomical Labelling atlas. We examined prognostic models driven by both "lesion load" in these regions (i.e. the proportion of each region destroyed by each patient's lesion), and by the disconnection of the white matter connections between them which was calculated via the Network Modification toolbox. Using these data, we build a series of prognostic models to predict first one ("naming"), and then all of the language scores defined by the CAT. We found no consistent evidence that connectivity disruption data in these models improved our ability to predict any language score. This may be because the connectivity disruption variables are strongly correlated with the lesion load variables: correlations which we measure both between pairs of variables in their original form, and between principal components of both datasets. Our conclusion is that, while both types of structural brain data do convey useful, prognostic information in this domain, they also appear to convey largely the same variance. We conclude that connectivity disruption variables do not help us to predict patients' language skills more accurately than lesion location (load) data alone.

A 67-year-old man developed a suspected adverse drug reaction during treatment with topical 5-fluorouracil (5-FU) for multiple actinic keratosis of the face, neck, and forearms. The man received topical 5-FU at a dosage of 0.5% for the actinic keratoses. After 1 week, he developed extreme lethargy, fatigue, fever, and mouth erosions. Several days later, and after discontinuation of 5-FU, painful mucositis and systemic side effects occurred, meeting criteria for hospitalization because of dehydration and a 6.8 kg weight loss. Hematology/oncology was consulted, and a possible systemic 5-FU reaction, similar to reactions to intravenous chemotherapy seen with a dihydropyrimidine dehydrogenase deficiency was suggested. The patient was not taking any concurrent medications, and he refused dihydropyrimidine dehydrogenase deficiency testing.

Dyslexia can have different manifestations: this has motivated different theories on its nature, on its underlying brain bases and enduring controversies on how to best treat it. The relative weight of the different manifestations has never been evaluated using both behavioural and fMRI measures, a challenge taken here to assess the major systems called into play in dyslexia by different theories. We found that adult well-compensated dyslexics were systematically impaired only in reading and in visuo-phonological tasks, while deficits for other systems (e.g., motor/cerebellar, visual magnocellular/motion perception) were only very occasional. In line with these findings, fMRI showed a reliable hypoactivation only for the task of reading, in the left occipito-temporal cortex (l-OTC). The l-OTC, normally a crossroad between the reading system and other systems, did not show the same level of intersection in dyslexics; yet, it was not totally silent because it responded, in segregated parts, during auditory phonological and visual motion perception tasks. This minimal behavioural and functional anatomical comorbidity demonstrates that a specific deficit of reading is the best description for developmental dyslexia, at least for adult well-compensated cases, with clear implications for rehabilitation strategies. The reduced intersection of multiple systems in the l-OTC suggests that dyslexics suffer from a coarser connectivity, leading to disconnection between the multiple domains that normally interact during reading., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Past attempts to identify the neural substrates of hand and finger imitation skills in the left hemisphere of the brain have yielded inconsistent results. Here, we analyse those associations in a large sample of 257 left hemisphere stroke patients. By introducing novel Bayesian methods, we characterise lesion symptom associations at three levels: the voxel-level, the single-region level (using anatomically defined regions), and the region-pair level. The results are inconsistent across those three levels and we argue that each level of analysis makes assumptions which constrain the results it can produce. Regardless of the inconsistencies across levels, and contrary to past studies which implicated differential neural substrates for hand and finger imitation, we find no consistent voxels or regions, where damage affects one imitation skill and not the other, at any of the three analysis levels. Our novel Bayesian approach indicates that any apparent differences appear to be driven by an increased sensitivity of hand imitation skills to lesions that also impair finger imitation. In our analyses, the results of the highest level of analysis (region-pairs) emphasise a role of the primary somatosensory and motor cortices, and the occipital lobe in imitation. We argue that this emphasis supports an account of both imitation tasks based on direct sensor-motor connections, which throws doubt on past accounts which imply the need for an intermediate (e.g. body-part-coding) system of representation., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

The Scale of Body Connection (SBC) was created to address the need for a self-report measure to examine body awareness and bodily dissociation in mind-body research. Developed in the U.S.A., it has been translated into many languages and tested for validity of scale translation. The burgeoning of mind-body research and the widespread use of the SBC scale underscored the need for critical assessment of the instrument's measurement properties. Thus, a broader evaluation of the SBC was designed using large samples from eight international, cross-sectional studies drawn from community (i.e., non-clinical) populations. Specifically, we assessed scale distribution properties and internal consistency reliabity, and using confirmatory factory analysis we evaluated scale contruct validity and compared male/female measurement models. The results indicated acceptable reliability for both the body awareness and bodily dissociation scales, and a good fit between the proposed theoretic model and the data, providing evidence of construct validity across all samples. Mean differences in body awareness were observed for males vs. females in most samples, with females generally showing higher body awareness compared to males. Multi-group structural equation modeling demonstrated a stable latent factor structure and factor loadings, indicating equivalent measurement models for males and females. In summary, this multi-sample study demonstrated SBC construct validity that supports its use in clinical research as a brief, readily translated, easy to administer measure of body awareness and bodily dissociation.

Searching for food is the first critical stage of foraging, and search efficiency is enhanced when foragers use cues from foods they seek. Yet we know little about food cues used by one major group of mammals, the herbivores, a highly interactive component of most ecosystems. How herbivores forage and what disrupts this process, both have significant ecological and evolutionary consequences beyond the animals themselves. Our aim was to investigate how free-ranging mammalian herbivores exploit leaf odour cues to find food plants amongst a natural and complex vegetation community. Our study system comprised the native "deer equivalent" of eastern Australian forests, the swamp wallaby Wallabia bicolor, and seedlings of Eucalyptus, the foundation tree genus in these ecosystems. We quantified how foraging wallabies responded to odour cues from plants manipulated in several ways: varying the quantity of visually concealed leaves, comparing damaged vs. undamaged leaves, and whole plants vs. those with suppressed cues. The rate of discovery of leaves by wallabies increased with odour cue magnitude, yet animals were extremely sensitive to even a tiny odour source of just a few leaves. Whole seedlings were discovered faster if their leaves were damaged. Wallabies found whole seedlings and those with suppressed visual cues equally rapidly, day and night. Seedlings with very little odour were discovered mainly by day, as nocturnal foraging success was severely disrupted. This study shows how leaf odour attracts mammalian herbivores to food plants, enabling non-random search for even tiny odour sources. As damaged leaves enhanced discovery, we suggest that the benefit of attracting natural enemies to invertebrate herbivores feeding on plants (potential "cry for help") may be offset by a cost-increased browsing by mammalian herbivores. This cost should be incorporated into multi-trophic plant-animal studies. Finally, the breakdown in capacity to find plants at night suggests substantial but unrecognized foraging costs to herbivores when abiotic factors, such as cold temperatures or pollution, reduce or degrade plant odour cues. We predict that an increasingly polluted world will alter the foraging success of mammalian herbivores, with significant ecological ramifications given that browsing can shape ecosystems., (© 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.)

To investigate how hearing status, sign language experience, and task demands influence functional responses in the human superior temporal cortices (STC) we collected fMRI data from deaf and hearing participants (male and female), who either acquired sign language early or late in life. Our stimuli in all tasks were pictures of objects. We varied the linguistic and visuospatial processing demands in three different tasks that involved decisions about (1) the sublexical (phonological) structure of the British Sign Language (BSL) signs for the objects, (2) the semantic category of the objects, and (3) the physical features of the objects.Neuroimaging data revealed that in participants who were deaf from birth, STC showed increased activation during visual processing tasks. Importantly, this differed across hemispheres. Right STC was consistently activated regardless of the task whereas left STC was sensitive to task demands. Significant activation was detected in the left STC only for the BSL phonological task. This task, we argue, placed greater demands on visuospatial processing than the other two tasks. In hearing signers, enhanced activation was absent in both left and right STC during all three tasks. Lateralization analyses demonstrated that the effect of deafness was more task-dependent in the left than the right STC whereas it was more task-independent in the right than the left STC. These findings indicate how the absence of auditory input from birth leads to dissociable and altered functions of left and right STC in deaf participants. SIGNIFICANCE STATEMENT Those born deaf can offer unique insights into neuroplasticity, in particular in regions of superior temporal cortex (STC) that primarily respond to auditory input in hearing people. Here we demonstrate that in those deaf from birth the left and the right STC have altered and dissociable functions. The right STC was activated regardless of demands on visual processing. In contrast, the left STC was sensitive to the demands of visuospatial processing. Furthermore, hearing signers, with the same sign language experience as the deaf participants, did not activate the STCs. Our data advance current understanding of neural plasticity by determining the differential effects that hearing status and task demands can have on left and right STC function., (Copyright © 2017 Twomey et al.)

Introduction: Aphasia is one of the most disabling sequelae after stroke, occurring in 25%-40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation., Trial Design: This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using 'Earobics' software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation., Methods: The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network., Results: Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG., Conclusions: Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex.Clinical trial registrationThis trial was registered with EudraCT (2005-004215-30, https:// eudract .ema.europa.eu/) and ISRCTN (68939136, http://www.isrctn.com/)., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Stroke survivors with acquired language deficits are commonly thought to reach a 'plateau' within a year of stroke onset, after which their residual language skills will remain stable. Nevertheless, there have been reports of patients who appear to recover over years. Here, we analysed longitudinal change in 28 left-hemisphere stroke patients, each more than a year post-stroke when first assessed-testing each patient's spoken object naming skills and acquiring structural brain scans twice. Some of the patients appeared to improve over time while others declined; both directions of change were associated with, and predictable given, structural adaptation in the intact right hemisphere of the brain. Contrary to the prevailing view that these patients' language skills are stable, these results imply that real change continues over years. The strongest brain-behaviour associations (the 'peak clusters') were in the anterior temporal lobe and the precentral gyrus. Using functional magnetic resonance imaging, we confirmed that both regions are actively involved when neurologically normal control subjects name visually presented objects, but neither appeared to be involved when the same participants used a finger press to make semantic association decisions on the same stimuli. This suggests that these regions serve word-retrieval or articulatory functions in the undamaged brain. We teased these interpretations apart by reference to change in other tasks. Consistent with the claim that the real change is occurring here, change in spoken object naming was correlated with change in two other similar tasks, spoken action naming and written object naming, each of which was independently associated with structural adaptation in similar (overlapping) right hemisphere regions. Change in written object naming, which requires word-retrieval but not articulation, was also significantly more correlated with both (i) change in spoken object naming; and (ii) structural adaptation in the two peak clusters, than was change in another task-auditory word repetition-which requires articulation but not word retrieval. This suggests that the changes in spoken object naming reflected variation at the level of word-retrieval processes. Surprisingly, given their qualitatively similar activation profiles, hypertrophy in the anterior temporal region was associated with improving behaviour, while hypertrophy in the precentral gyrus was associated with declining behaviour. We predict that either or both of these regions might be fruitful targets for neural stimulation studies (suppressing the precentral region and/or enhancing the anterior temporal region), aiming to encourage recovery or arrest decline even years after stroke occurs., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Transcranial magnetic stimulation focused on either the left anterior supramarginal gyrus or opercular part of the left inferior frontal gyrus has been reported to transiently impair the ability to perform phonological more than semantic tasks. Here we tested whether phonological processing abilities were also impaired following lesions to these regions in right-handed, English speaking adults, who were investigated at least 1 year after a left-hemisphere stroke. When our regions of interest were limited to 0.5 cm3 of grey matter centred around sites that had been identified with transcranial magnetic stimulation-based functional localization, phonological impairments were observed in 74% (40/54) of patients with damage to the regions and 21% (21/100) of patients sparing these regions. This classification accuracy was better than that observed when using regions of interest centred on activation sites in previous functional magnetic resonance imaging studies of phonological processing, or transcranial magnetic stimulation sites that did not use functional localization. New regions of interest were generated by redefining the borders of each of the transcranial magnetic stimulation sites to include areas that were consistently damaged in the patients with phonological impairments. This increased the incidence of phonological impairments in the presence of damage to 85% (46/54) and also reduced the incidence of phonological impairments in the absence of damage to 15% (15/100). The difference in phonological processing abilities between those with and without damage to these 'transcranial magnetic stimulation-guided' regions remained highly significant even after controlling for the effect of lesion size. The classification accuracy of the transcranial magnetic stimulation-guided regions was validated in a second sample of 108 patients and found to be better than that for (i) functional magnetic resonance imaging-guided regions; (ii) a region identified from an unguided lesion overlap map; and (iii) a region identified from voxel-based lesion-symptom mapping. Finally, consistent with prior findings from functional imaging and transcranial magnetic stimulation in healthy participants, we show how damage to our transcranial magnetic stimulation-guided regions affected performance on phonologically more than semantically demanding tasks. The observation that phonological processing abilities were impaired years after the stroke, suggests that other brain regions were not able to fully compensate for the contribution that the transcranial magnetic stimulation-guided regions make to language tasks. More generally, our novel transcranial magnetic stimulation-guided lesion-deficit mapping approach shows how non-invasive stimulation of the healthy brain can be used to guide the identification of regions where brain damage is likely to cause persistent behavioural effects., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Understanding the brain mechanisms involved in diagnostic reasoning may contribute to the development of methods that reduce errors in medical practice. In this study we identified similar brain systems for diagnosing diseases, prescribing treatments, and naming animals and objects using written information as stimuli. Employing time resolved modeling of blood oxygen level dependent (BOLD) responses enabled time resolved (400 milliseconds epochs) analyses. With this approach it was possible to study neural processes during successive stages of decision making. Our results showed that highly diagnostic information, reducing uncertainty about the diagnosis, decreased monitoring activity in the frontoparietal attentional network and may contribute to premature diagnostic closure, an important cause of diagnostic errors. We observed an unexpected and remarkable switch of BOLD activity within a right lateralized set of brain regions related to awareness and auditory monitoring at the point of responding. We propose that this neurophysiological response is the neural substrate of awareness of one's own (verbal) response. Our results highlight the intimate relation between attentional mechanisms, uncertainty, and decision making and may assist the advance of approaches to prevent premature diagnostic closure.

Substance use is a complex clinical problem characterized by emotion dysregulation and daily challenges that can interfere with laboratory research. Thus, few psychophysiological studies examine autonomic and self-report measures of emotion dysregulation with multidiagnostic, chemically dependent samples or extend this work into naturalistic settings. In this study, we used a within-subject design to examine changes in respiratory sinus arrhythmia (RSA), electrodermal activity (EDA), and self-reported affect across three tasks designed to elicit distinct psychophysiological and emotional response patterns. We also examined emotion dysregulation as a moderator of psychophysiological responses. Participants include 116 women with multiple comorbid mental health conditions enrolled in substance use treatment, many of whom also reported high emotion dysregulation. Participants were assessed in the treatment setting and completed three tasks: watching a sad movie clip, rumination on a stressful event, and a mindful interoceptive awareness meditation. Multilevel models were used to examine changes from resting baselines to the tasks. During the film, results indicate a significant decrease in RSA and an increase in EDA. For the rumination task, participants showed a decrease in RSA but no EDA response. For the body awareness task, there was an increase in RSA and a decrease in EDA. Emotion dysregulation was associated with differences in baseline RSA but not with EDA or with the slope of response patterns across tasks. Self-reported affect was largely consistent with autonomic patterns. Findings add to the literature on emotion dysregulation, substance use, and the translation of psychophysiological measurements into clinical settings with complex samples., (© 2017 Society for Psychophysiological Research.)

How animals locate nutritious but camouflaged prey items with increasing accuracy is not well understood. Olfactory foraging is common in vertebrates and the nutritional desirability of food should influence the salience of odour cues. We used signal detection analysis to test the effect of nutritional value relative to the conspicuousness of food patches on rates of foraging improvement of wild house mice Mus musculus searching for buried food (preferred peanuts or non-preferred barley). Olfactory cues were arranged to make food patches conspicuous or difficult to distinguish using a novel form of olfactory camouflage. Regardless of food type or abundance, mice searching for conspicuous food patches performed significantly better than mice searching for camouflaged patches. However, food type influenced how mice responded to different levels of conspicuousness. Mice searching for peanuts improved by similar rates regardless of whether food was easy or hard to find, but mice searching for barley showed significant differences, improving rapidly when food was conspicuous but declining in accuracy when food was camouflaged. Our results demonstrate a fundamental tenet of olfactory foraging that nutritional desirability influences rates of improvement in odour discrimination, enabling nutritious but camouflaged prey to be located with increasing efficiency., (© 2017 The Author(s).)

In this paper, we consider solutions to ten of the challenges faced when trying to predict an individual's functional outcome after stroke on the basis of lesion site. A primary goal is to find lesion-outcome associations that are consistently observed in large populations of stroke patients because consistent associations maximise confidence in future individualised predictions. To understand and control multiple sources of inter-patient variability, we need to systematically investigate each contributing factor and how each factor depends on other factors. This requires very large cohorts of patients, who differ from one another in typical and measurable ways, including lesion site, lesion size, functional outcome and time post stroke (weeks to decades). These multivariate investigations are complex, particularly when the contributions of different variables interact with one another. Machine learning algorithms can help to identify the most influential variables and indicate dependencies between different factors. Multivariate lesion analyses are needed to understand how the effect of damage to one brain region depends on damage or preservation in other brain regions. Such data-led investigations can reveal predictive relationships between lesion site and outcome. However, to understand and improve the predictions we need explanatory models of the neural networks and degenerate pathways that support functions of interest. This will entail integrating the results of lesion analyses with those from functional imaging (fMRI, MEG), transcranial magnetic stimulation (TMS) and diffusor tensor imaging (DTI) studies of healthy participants and patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Poor communication between academic researchers and wildlife managers limits conservation progress and innovation. As a result, input from overlapping fields, such as animal behaviour, is underused in conservation management despite its demonstrated utility as a conservation tool and countless papers advocating its use. Communication and collaboration across these two disciplines are unlikely to improve without clearly identified management needs and demonstrable impacts of behavioural-based conservation management. To facilitate this process, a team of wildlife managers and animal behaviour researchers conducted a research prioritisation exercise, identifying 50 key questions that have great potential to resolve critical conservation and management problems. The resulting agenda highlights the diversity and extent of advances that both fields could achieve through collaboration., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We used fMRI in 85 healthy participants to investigate whether different parts of the left supramarginal gyrus (SMG) are involved in processing phonological inputs and outputs. The experiment involved 2 tasks (speech production (SP) and one-back (OB) matching) on 8 different types of stimuli that systematically varied the demands on sensory processing (visual vs. auditory), sublexical phonological input (words and pseudowords vs. nonverbal stimuli), and semantic content (words and objects vs. pseudowords and meaningless baseline stimuli). In ventral SMG, we found an anterior subregion associated with articulatory sequencing (for SP > OB matching) and a posterior subregion associated with auditory short-term memory (for all auditory > visual stimuli and written words and pseudowords > objects). In dorsal SMG, a posterior subregion was most highly activated by words, indicating a role in the integration of sublexical and lexical cues. In anterior dorsal SMG, activation was higher for both pseudoword reading and object naming compared with word reading, which is more consistent with executive demands than phonological processing. The dissociation of these four "functionally-distinct" regions, all within left SMG, has implications for differentiating between different types of phonological processing, understanding the functional anatomy of language and predicting the effect of brain damage., (© The Author 2016. Published by Oxford University Press.)

If generalist predators are to hunt efficiently, they must track the changing costs and benefits of multiple prey types. Decisions to switch from hunting preferred prey to alternate prey have been assumed to be driven by decreasing availability of preferred prey, with less regard for accessibility of alternate prey. Olfactory cues from prey provide information about prey availability and its location, and are exploited by many predators to reduce search costs. We show that stoats Mustela erminea, an alien olfactory predator in New Zealand, are sensitive to the search costs of hunting both their preferred rodent prey (mice) and a less desirable alternate prey (locust). We manipulated search costs for stoats using a novel form of olfactory camouflage of both prey, and found that stoats altered their foraging strategy depending on whether mice were camouflaged or conspicuous, but only when locusts were also camouflaged. Stoats gave up foraging four times more often when both prey were camouflaged, compared to when mice were conspicuous and locusts camouflaged. There were no differences in the foraging strategies used to hunt camouflaged or conspicuous mice when locusts were easy to find. Consequently, camouflaged mice survived longer than conspicuous mice when locusts were hard to find, but not when locusts were easy to find. Our results demonstrate that predators can integrate search costs from multiple prey types when making foraging decisions. Manipulating olfactory search costs to alter foraging strategies offers new methods for understanding the factors that foreshadow prey switching.