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Aim: Physical activity (PA) is a key component for brain health and Reserve, and it is among the main dementia protective factors. However, the neurobiological mechanisms underpinning Reserve are not fully understood. In this regard, a noradrenergic (NA) theory of cognitive reserve (Robertson, 2013) has proposed that the upregulation of NA system might be a key factor for building reserve and resilience to neurodegeneration because of the neuroprotective role of NA across the brain. PA elicits an enhanced catecholamine response, in particular for NA. By increasing physical commitment, a greater amount of NA is synthetised in response to higher oxygen demand. More physically trained individuals show greater capabilities to carry oxygen resulting in greater Vo2max – a measure of oxygen uptake and physical fitness (PF). Methods: We hypothesized that greater Vo2max would be related to greater Locus Coeruleus (LC) MRI signal intensity. In a sample of 41 healthy subjects, we performed Voxel‐Based Morphometry analyses, then repeated for the other neuromodulators as a control procedure (Serotonin, Dopamine and Acetylcholine). Results: As hypothesized, greater Vo2max related to greater LC signal intensity, and weaker associations emerged for the other neuromodulators. Conclusion: This newly established link between Vo2max and LC–NA system offers further understanding of the neurobiology underpinning Reserve in relationship to PA. While this study supports Robertson's theory proposing the upregulation of the NA system as a possible key factor building Reserve, it also provides ground for increasing LC–NA system resilience to neurodegeneration via Vo2max enhancement. [ABSTRACT FROM AUTHOR]

An office on the first floor of the Theatre Royal, Haymarket has six images painted directly on the walls that have remarkably survived many redecorations. This room was actor-manager Cyril Maude's dressing room between 1896 and 1905 when he was joint manager of the Theatre Royal alongside Frederick Harrison. To its fullest extent, Maude's exceptional dressing room was adorned with a gallery of forty images created in greasepaint by fellow actors and friends. Famous cartoonists Phil May, Harry Furniss, Bernard Partridge, Leonard Raven-Hill and Leslie Ward left their mark. The greasepaint gallery can be read as an extension of the fashion for collecting autographs; most of the images were signed and some dated. Equally, the gallery acts as a nostalgic scrapbook commemorating productions and recording famous visitors who were granted entrée behind the scenes. The gallery signalled Maude's standing in artistic, literary and social circles and thereby reinforced his own celebrity status. [ABSTRACT FROM AUTHOR]

Background: Stress exposure in childhood and adolescence has been linked to reductions in cortical structures and cognitive functioning. However, to date, most of these studies have been cross‐sectional, limiting the ability to make long‐term inferences, given that most cortical structures continue to develop through adolescence. Methods: Here, we used a subset of the IMAGEN population cohort sample (N = 502; assessment ages: 14, 19, and 22 years; mean age: 21.945 years; SD = 0.610) to understand longitudinally the long‐term interrelations between stress, cortical development, and cognitive functioning. To these ends, we first used a latent change score model to examine four bivariate relations – assessing individual differences in change in the relations between adolescent stress exposure and volume, surface area, and cortical thickness of cortical structures, as well as cognitive outcomes. Second, we probed for indirect neurocognitive effects linking stress to cortical brain structures and cognitive functions using rich longitudinal mediation modeling. Results: Latent change score modeling showed that greater baseline adolescence stress at age 14 predicted a small reduction in the right anterior cingulate volume (Std. β = −.327, p =.042, 95% CI [−0.643, −0.012]) and right anterior cingulate surface area (Std. β = −.274, p =.038, 95% CI [−0.533, −0.015]) across ages 14–22. These effects were very modest in nature and became nonsignificant after correcting for multiple comparisons. Our longitudinal analyses found no evidence of indirect effects in the two neurocognitive pathways linking adolescent stress to brain and cognitive outcomes. Conclusion: Findings shed light on the impact of stress on brain reductions, particularly in the prefrontal cortex that have consistently been implicated in the previous cross‐sectional studies. However, the magnitude of effects observed in our study is smaller than that has been reported in past cross‐sectional work. This suggests that the potential impact of stress during adolescence on brain structures may likely be more modest than previously noted. [ABSTRACT FROM AUTHOR]

Cognitive reserve supports cognitive function in the presence of pathology or atrophy. Functional neuroimaging may enable direct and accurate measurement of cognitive reserve which could have considerable clinical potential. The present study aimed to develop and validate a measure of cognitive reserve using task‐based fMRI data that could then be applied to independent resting‐state data. Connectome‐based predictive modelling with leave‐one‐out cross‐validation was applied to predict a residual measure of cognitive reserve using task‐based functional connectivity from the Cognitive Reserve/Reference Ability Neural Network studies (n = 220, mean age = 51.91 years, SD = 17.04 years). This model generated summary measures of connectivity strength that accurately predicted a residual measure of cognitive reserve in unseen participants. The theoretical validity of these measures was established via a positive correlation with a socio‐behavioural proxy of cognitive reserve (verbal intelligence) and a positive correlation with global cognition, independent of brain structure. This fitted model was then applied to external test data: resting‐state functional connectivity data from The Irish Longitudinal Study on Ageing (TILDA, n = 294, mean age = 68.3 years, SD = 7.18 years). The network‐strength predicted measures were not positively associated with a residual measure of cognitive reserve nor with measures of verbal intelligence and global cognition. The present study demonstrated that task‐based functional connectivity data can be used to generate theoretically valid measures of cognitive reserve. Further work is needed to establish if, and how, measures of cognitive reserve derived from task‐based functional connectivity can be applied to independent resting‐state data. [ABSTRACT FROM AUTHOR]

After the cessation of conflict the majority of those involved in violations of international law will not be held criminally accountable. Rather, it is frequently the case that the bulk of perpetrators receive amnesty. Often, consequentialist considerations weigh heavily on the decision to grant amnesty. For instance, amnesties may be offered in order to generate aggregate security benefits in volatile post-conflict settings. My contention is that states cannot morally justify amnesties by appealing solely to the aggregate benefits they are expected to deliver. The moral objection concerns the distribution of associated costs, where such costs include the risk of re-offense that amnesty generates. Importantly, these costs may be unevenly imposed onto the society. This means that certain citizens will expect to bear individual losses greater than any gains the amnesty can deliver to them. Those placed at a net-disadvantage can object that amnesties are morally unjustifiable: they impose unreasonable burdens on them in order to secure benefits for others. However, as amnesties are often vital to achieve peace there remain strong pragmatic reasons to favour limited prosecutions. Given these concerns it is necessary to justify the differential imposition of cost associated with amnesties. I argue that ex ante contractualism, as a theory of moral justification, is well-suited to this task. According to this framework amnesties are justified only if no individual could reasonably reject the associated burdens. By developing a non-aggregative justification of amnesty this account offers a novel approach to the design and implementation of post-conflict prosecutorial strategies. [ABSTRACT FROM AUTHOR]

Neural oscillations, or brain rhythms, fluctuate in a manner reflecting ongoing behavior. Whether these fluctuations are instrumental or epiphenomenal to the behavior remains elusive. Attempts to experimentally manipulate neural oscillations exogenously using noninvasive brain stimulation have shown some promise, but difficulty with tailoring stimulation parameters to individuals has hindered progress in this field. We demonstrate here using electroencephalography (EEG) neurofeedback in a brain‐computer interface that human participants (n = 44) learned over multiple sessions across a 6‐day period to self‐regulate their Beta rhythm (13–20 Hz), either up or down, over the right inferior frontal cortex. Training to downregulate Beta was more effective than training to upregulate Beta. The modulation was evident only during neurofeedback task performance but did not lead to offline alteration of Beta rhythm characteristics at rest, nor to changes in subsequent cognitive behavior. Likewise, a control group (n = 38) who underwent training to up or downregulate the Alpha rhythm (8–12 Hz) did not exhibit behavioral changes. Although the right frontal Beta rhythm has been repeatedly implicated as a key component of the brain's inhibitory control system, the present data suggest that its manipulation offline prior to cognitive task performance does not result in behavioral change in healthy individuals. Whether this form of neurofeedback training could serve as a useful therapeutic target for disorders with dysfunctional inhibitory control as their basis remains to be tested in a context where performance is abnormally poor and neural dynamics are different. Using a non‐invasive brain‐computer interface, volitional self‐regulation of the right frontal Beta rhythm was achieved in the absence of exogenous brain stimulation. However, this modulation had no impact on behavior in healthy individuals. Whether this form of neurofeedback training could serve as a useful therapeutic target for disorders with dysfunctional inhibitory control as their basis remains to be tested in a context where performance is abnormally poor and neural dynamics are different. [ABSTRACT FROM AUTHOR]

Serotinous plants that both release seed and resprout after fire are thought to be resistant to wildfires within the range of intensities that have been experienced up until now. However, the frequency and scale of intense wildfires is increasing under climate change. We studied annual flowering and fruit‐set in a large population of Banksia spinulosa plants in south‐eastern Australia from the early 1990s to 2006. The results led us to predict that there would be little recruitment from seedlings after the next fire but good resprouting from very long‐lived lignotubers. Our study population burned in the widespread, high‐intensity wildfires of December 2019, providing an opportunity to test the hypothesis. Most above‐ground stems and cones were reduced to ash, and only 15 cones (on 10 plants) remained after the fire. We found no seedlings in the 0.3 ha site that had initially contained over 350 adult plants. Little natural mortality had been observed pre‐fire, but by 5 months after the fire, nearly 25% of lignotubers had failed to resprout. We conclude that even common and widespread resprouting species will suffer population decline and reduced genetic diversity as high‐intensity fires become more extensive and frequent. [ABSTRACT FROM AUTHOR]

Objective: Research in adolescent depression has found aberrant intrinsic functional connectivity (iFC) among the ventral striatum (VS) and several brain regions implicated in reward processing. The present study probes this question by taking advantage of the availability of data from a large youth cohort, the IMAGEN Consortium.Methods: iFC data from 303 adolescents (48% of them female) were used to examine associations of VS connectivity at baseline (at age 14) with depressive disorders at baseline and at 2-year (N=250) and 4-year (N=219) follow-ups. Eleven regions of interest, key nodes of the reward system, were used to probe the reward network and calculate the connectivity strength of the VS within this network (VS connectivityrw). The main analyses assessed associations of VS connectivityrw with depressive disorders, anhedonia, and low mood using logistic regression. Autoregressive models accounting for carryover effects over time were conducted to further evaluate these brain-behavior associations.Results: Higher right VS connectivityrw was associated with higher probability of depressive disorders at baseline (odds ratio=2.65, 95% CI=1.40, 5.05). This finding was confirmed in the autoregressive model, adjusting for carryover effects of the depressive disorders across the three time points. VS connectivityrw was not predictive of depressive disorders at follow-up assessments. Longitudinal associations between VS connectivityrw and anhedonia emerged in the structural equation model: left VS connectivityrw was associated with anhedonia at 2 years (odds ratio=2.20, 95% CI=1.54, 3.14), and right VS connectivityrw was linked to anhedonia at 4 years (odds ratio=1.87, 95% CI=1.09, 3.21). VS connectivityrw did not predict low mood at any time point in the structural equation model.Conclusions: The connectivity strength of the VS within the reward network showed distinct patterns of association with depressive disorders and anhedonia from mid to late adolescence, suggesting that the role of this circuitry in depression changes with age. This study replicates, in an independent sample, the association between the VS and depression previously reported in younger adolescents. The findings suggest a role of VS connectivityrw in anhedonia but not in low mood. [ABSTRACT FROM AUTHOR]

The challenges facing I Banksia i species conservation in the south-eastern state of Victoria were the focus of an online workshop in May 2020. Banksias are iconic Australian plants, with a Gondwanan origin. [Extracted from the article]

Alcohol use disorder is characterised by disrupted reward learning, underpinned by dysfunctional cortico-striatal reward pathways, although relatively little is known about the biology of reward processing in populations who engage in risky alcohol use. Cues that trigger reward anticipation can be categorized according to their learnt valence (i.e., positive vs. negative outcomes) and motivational salience (i.e., incentive vs. neutral cues). Separating EEG signals associated with these dimensions is challenging because of their inherent collinearity, but the recent application of machine learning methods to single EEG trials affords a solution. Here, the Alcohol Use Disorders Identification Test (AUDIT) was used to quantify risky alcohol use, with participants split into high alcohol (HA) (n = 22, mean AUDIT score: 13.82) and low alcohol (LA) (n = 22, mean AUDIT score: 5.77) groups. We applied machine learning multivariate single-trial classification to the electroencephalography (EEG) data collected during reward anticipation. The LA group demonstrated significant valence discrimination in the early stages of reward anticipation within the cue-P3 time window (400-550 ms), whereas the HA group was insensitive to valence within this time window. Notably, the LA, but not the HA group demonstrated a relationship between single-trial variability in the early valence component and reaction times for gain and loss trials. This study evidences disrupted hypoactive valence sensitivity in the HA group, revealing potential neurophysiological markers for risky drinking behaviours which place individuals at-risk of adverse health events. [ABSTRACT FROM AUTHOR]

Depressed individuals use language differently than healthy controls and it has been proposed that social media posts can be used to identify depression. Much of the evidence behind this claim relies on indirect measures of mental health and few studies have tested if these language features are specific to depression versus other aspects of mental health. We analysed the Tweets of 1006 participants who completed questionnaires assessing symptoms of depression and 8 other mental health conditions. Daily Tweets were subjected to textual analysis and the resulting linguistic features were used to train an Elastic Net model on depression severity, using nested cross-validation. We then tested performance in a held-out test set (30%), comparing predictions of depression versus 8 other aspects of mental health. The depression trained model had modest out-of-sample predictive performance, explaining 2.5% of variance in depression symptoms (R2 = 0.025, r = 0.16). The performance of this model was as-good or superior when used to identify other aspects of mental health: schizotypy, social anxiety, eating disorders, generalised anxiety, above chance for obsessive-compulsive disorder, apathy, but not significant for alcohol abuse or impulsivity. Machine learning analysis of social media data, when trained on well-validated clinical instruments, could not make meaningful individualised predictions regarding users' mental health. Furthermore, language use associated with depression was non-specific, having similar performance in predicting other mental health problems. [ABSTRACT FROM AUTHOR]

Prominent Kantian scholars, such as Korsgaard and Waldron, claim that the very existence of juridical-political institutions is sufficient to render laws authoritative. Critics argue that this view is unpersuasive as it requires subjects to obey grossly unjust laws. Here, I identify two problems facing scholars who reject the absolutist view of political authority proffered by Korsgaard and Waldron. First, when there is reasonable disagreement regarding a law's legitimacy the Principle of Right generates contradictory obligations as it commands both disobedience and compliance. In clarifying this problem, I argue that individuals must disobey illegitimate laws where this requirement is co-extensive with the duty to leave the state of nature. However, disobedience amounts to domination when individuals are subjected to private judgments regarding the conditions of freedom. The Principle of Right cannot overcome this impasse as it does not offer reasons in favor of compliance that are distinct from those reasons legitimating the law. To address this issue, I supplement Kant's account with Joseph Raz's 'service conception' of authority to show that compliance can be rendered compatible with the Principle of Right. A second problem emerges when laws are blatantly illegitimate such that obedience cannot be justified. In these cases, the Principle of Right cannot guide legislative reform in an intuitively appealing way as it fails to address considerations of proportionality. Though this latter problem is not resolved here, identifying it helps to further clarify the relationship between Kant's moral and political principles. [ABSTRACT FROM AUTHOR]

In humans, impaired response inhibition is characteristic of a wide range of psychiatric diseases and of normal aging. It is hypothesized that the right inferior frontal cortex (rIFC) plays a key role by inhibiting the motor cortex via the basal ganglia. The electroencephalography (EEG)-derived b-rhythm (15-29 Hz) is thought to reflect communication within this network, with increased right frontal b-power often observed before successful response inhibition. Recent literature suggests that averaging spectral power obscures the transient, burst-like nature of b-activity. There is evidence that the rate of b-bursts following a Stop signal is higher when a motor response is successfully inhibited. However, other characteristics of b-burst events, and their topographical properties, have not yet been examined. Here, we used a large human (male and female) EEG Stop Signal task (SST) dataset (n = 218) to examine averaged normalized b-power, b-burst rate, and b-burst "volume" (which we defined as burst duration 3 frequency span 3 amplitude). We first sought to optimize the b-burst detection method. In order to find predictors across the whole scalp, and with high temporal precision, we then used machine learning to (1) classify successful versus failed stopping and to (2) predict individual stop signal reaction time (SSRT). b-burst volume was significantly more predictive of successful and fast stopping than b-burst rate and normalized b-power. The classification model generalized to an external dataset (n = 201). We suggest b-burst volume is a sensitive and reliable measure for investigation of human response inhibition. [ABSTRACT FROM AUTHOR]

Brain-predicted age difference scores are calculated by subtracting chronological age from 'brain' age, which is estimated using neuroimaging data. Positive scores reflect accelerated ageing and are associated with increased mortality risk and poorer physical function. To date, however, the relationship between brain-predicted age difference scores and specific cognitive functions has not been systematically examined using appropriate statistical methods. First, applying machine learning to 1359 T1-weighted MRI scans, we predicted the relationship between chronological age and voxel-wise grey matter data. This model was then applied to MRI data from three independent datasets, significantly predicting chronological age in each dataset: Dokuz Eylül University (n = 175), the Cognitive Reserve/Reference Ability Neural Network study (n = 380), and The Irish Longitudinal Study on Ageing (n = 487). Each independent dataset had rich neuropsychological data. Brain-predicted age difference scores were significantly negatively correlated with performance on measures of general cognitive status (two datasets); processing speed, visual attention, and cognitive flexibility (three datasets); visual attention and cognitive flexibility (two datasets); and semantic verbal fluency (two datasets). As such, there is firm evidence of correlations between increased brain-predicted age differences and reduced cognitive function in some domains that are implicated in cognitive ageing. [ABSTRACT FROM AUTHOR]

Previous studies suggest that individuals with substance use disorder have abnormally large responses to unexpected outcomes (reward prediction errors [RPEs]). However, there is much less information on RPE in individuals at risk of alcohol misuse, prior to neurobiological adaptations that might result from sustained alcohol use. Here, participants (mean age 23.77 years, range 18-32 years) performed the electrophysiological monetary incentive delay task. This task involved responding to a target stimulus following reward incentive cues to win, or avoid losing, the cued reward while brain activity was recorded under 64-channel EEG. The Alcohol Use Disorders Identification Test (AUDIT) was used to quantify at-risk alcohol use, with high (n = 22, mean AUDIT score: 13.82) and low (n = 22, mean AUDIT score: 5.77) alcohol use groups. Trial-by-trial RPEs were estimated using a Rescorla-Wagner reinforcement model based on behavioral data. A single-trial analysis revealed that the feedback-related negativity (FRN) and feedback P3 (fb-P3) event-related potential components were significantly modulated by RPEs. There was increased RPE-related fb-P3 amplitude for those in the high alcohol use group. Next, the mean amplitude of ERPs elicited by positive and negative RPEs were compared between groups. We found that high alcohol use participants had attenuated FRN amplitude in contrast with low alcohol use participants for both positive and negative RPEs but enhanced fb-P3 for both positive and negative RPE. These results, with differences in RPE in an at-risk group, suggest that RPE a potential vulnerability marker for alcohol use disorder. [ABSTRACT FROM AUTHOR]

The survival of an organism depends on the ability to make adaptive decisions to achieve the needs of the organism: where to get food, who to mate with, and how to evade predators. Decision-making is a term used to describe a collection of behavioral and/or computational functions that guide the selection of an option amongst a set of alternatives. Some of these functions may include calculating the costs and benefits of a particular action, evaluating differences in value of each of the alternative outcomes and the likelihood of receiving a particular outcome, using past experiences to generate predictions or expectations about action-outcome associations, and/or integration of past experiences to make novel inferences that can be used in new environments. There is considerable interest in understanding the neurobiological mechanisms that mediate these decision-making functions and recent advances in behavioral approaches, neuroscience techniques, and neuroimaging measures have begun to develop mechanistic links between biology, reward, and decision making. This multidisciplinary work holds great promise for elucidating the biological mechanisms mediating decision-making deficits in normal and abnormal states. The multidisciplinary studies included in this Collection provide new insights into the neuroscience of decision making and reward. [ABSTRACT FROM AUTHOR]

It is often assumed that long‐lived woody perennials with canopy‐stored seed banks steadily accumulate seeds over time since fire. Trends in flowering and fruiting have usually been inferred from synchronic studies of sites of different post‐fire ages or counting stored seeds in apparent age classes, and mostly in obligate‐seeder species. Long‐term longitudinal studies on a broader range of species are needed to fully understand the dynamics of flower and fruit production and accumulation of viable seeds. Key questions are as follows: What is the annual trend in flowering and cone production? Is this matched by accumulation of cones and seeds? How is seed germinability related to cone age at the time of a fire?We counted inflorescences and tagged cones produced annually by the resprouting shrub Banksia spinulosa in 315 plants over 13 years at one site and in 46 plants over 20 years at another. At the end of the study, we harvested all accumulated cones, burned them and assessed seed viability using germination trials.We detected enormous inter‐plant variation in reproductive effort and output. 50% of inflorescences was produced by only 10%–15% of plants. There was a potential for accumulation of massive seed banks. However, (a) only 8%–10% of inflorescences became cones; (b) only 44%–50% of these were retained until harvest; (c) many retained cones suffered seed predation; and (d) viability of retained seeds declined with cone age. The result of these processes meant that the accumulated seed bank was only two to four seeds per plant, 82%–94% of the viable seeds had been produced in 6 years prior to harvest and only 12%–26% of plants contributed to this viable seed bank.Synthesis: Cone and seed losses and declining seed viability in B. spinulosa mean that almost all viable seeds come from the past few years of flowering even though apparently intact cones may be retained for decades. If this is typical for resprouting serotinous shrubs, it is important to understand trends in flowering and fruit set over time because the magnitude of recruitment will depend on fecundity in the few years prior to a fire. [ABSTRACT FROM AUTHOR]

Contralateral delay activity (CDA) has been proposed as a pre‐clinical neural marker for mild cognitive impairment (MCI). However, existing evidence is limited to one study with a small sample size (n = 24). Our aim was to extend previous work by investigating the relationship between the CDA and MCI risk in a large sample of older adults (n = 76). We used a regression approach to determine whether (and when) CDA amplitude predicted MCI risk, as indexed by the Montreal Cognitive Assessment (MoCA). CDA amplitude from ~300‐500 and ~800‐900 ms predicted MoCA performance. However, significant effects were only observed for specific electrodes (P5/P6 and CP3/CP4, but not PO7/PO8) and the nature of the relationship between the CDA and MoCA scores differed across time and according to set size. Bayesian regression analysis indicated partial evidence in favour of the null hypothesis (BF10 values = 4–1.18). Contrary to previous results, our findings suggest that the CDA may not a robust marker of MCI risk. More broadly, our results highlight the difficulty in identifying at‐risk individuals, particularly as MCI is a heterogeneous, unstable condition. Future research should prioritise longitudinal approaches in order to track the progression of the CDA and its association with cognitive decline in later life. [ABSTRACT FROM AUTHOR]

Adults with attention‐deficit/hyperactivity disorder (ADHD) have been described as having altered resting‐state electroencephalographic (EEG) spectral power and theta/beta ratio (TBR). However, a recent review (Pulini et al. 2018) identified methodological errors in neuroimaging, including EEG, ADHD classification studies. Therefore, the specific EEG neuromarkers of adult ADHD remain to be identified, as do the EEG characteristics that mediate between genes and behaviour (mediational endophenotypes). Resting‐state eyes‐open and eyes‐closed EEG was measured from 38 adults with ADHD, 45 first‐degree relatives of people with ADHD and 51 unrelated controls. A machine learning classification analysis using penalized logistic regression (Elastic Net) examined if EEG spectral power (1–45 Hz) and TBR could classify participants into ADHD, first‐degree relatives and/or control groups. Random‐label permutation was used to quantify any bias in the analysis. Eyes‐open absolute and relative EEG power distinguished ADHD from control participants (area under receiver operating characteristic = 0.71–0.77). The best predictors of ADHD status were increased power in delta, theta and low‐alpha over centro‐parietal regions, and in frontal low‐beta and parietal mid‐beta. TBR did not successfully classify ADHD status. Elevated eyes‐open power in delta, theta, low‐alpha and low‐beta distinguished first‐degree relatives from controls (area under receiver operating characteristic = 0.68–0.72), suggesting that these features may be a mediational endophenotype for adult ADHD. Resting‐state EEG spectral power may be a neuromarker and mediational endophenotype of adult ADHD. These results did not support TBR as a diagnostic neuromarker for ADHD. It is possible that TBR is a characteristic of childhood ADHD. [ABSTRACT FROM AUTHOR]

There exists uncertainty for clinicians over how the separate subcomponent processes of psychological flexibility, a core construct of the Acceptance and Commitment Therapy model, interact and influence distress experienced. The present study (N = 567) employed latent class analysis to (a) identify potential classes (i.e., subgroups) of psychological flexibility based on responses on measures of key subcomponent process and (b) examine whether such classes could reliably differentiate levels of self-reported psychological distress and positive and negative emotionality. We found three distinct classes: (a) High Psychological Flexibility, (b) Moderate Psychological Flexibility, and (c) Low Psychological Flexibility. Those in the Low Psychology Flexibility class reported highest levels of psychological distress, whereas those in the High Psychological Flexibility class reported lowest levels of psychological distress. This study provides a clearer view to clinicians of the profile of the broader spectrum of the psychological flexibility model to facilitate change in clients. [ABSTRACT FROM AUTHOR]

In this study we have assessed the effects of increased cortisol levels during early embryonic development on immune function in zebrafish (Danio rerio) larvae. Fertilized eggs were exposed to either a cortisol-containing, a dexamethasone-containing (to stimulate the glucocorticoid receptor selectively) or a control medium for 6 h post-fertilization (0–6 hpf). First, we measured baseline expression of a number of immune-related genes (socs3a, mpeg1.1, mpeg1.2 , and irg1l) 5 days post-fertilization (dpf) in larvae of the AB and TL strain to assess the effectiveness of our exposure procedure and potential strain differences. Cortisol and dexamethasone strongly up-regulated baseline expression of these genes independent of strain. The next series of experiments were therefore carried out in larvae of the AB strain only. We measured neutrophil/macrophage recruitment following tail fin amputation (performed at 3 dpf) and phenotypical changes as well as survival following LPS-induced sepsis (150 μg/ml; 4–5 dpf). Dexamethasone, but not cortisol, exposure at 0–6 hpf enhanced neutrophil recruitment 4 h post tail fin amputation. Cortisol and dexamethasone exposure at 0–6 hpf led to a milder phenotype (e.g., less tail fin damage) and enhanced survival following LPS challenge compared to control exposure. Gene-expression analysis showed accompanying differences in transcript abundance of tlr4bb, cxcr4a, myd88, il1 β , and il10. These data show that early-life exposure to cortisol, which may be considered to be a model or proxy of maternal stress, induces an adaptive response to immune challenges, which seems mediated via the glucocorticoid receptor. [ABSTRACT FROM AUTHOR]

Cannabis use initiated during adolescence might precipitate negative consequences in adulthood. Thus, predicting adolescent cannabis use prior to any exposure will inform the aetiology of substance abuse by disentangling predictors from consequences of use. In this prediction study, data were drawn from the IMAGEN sample, a longitudinal study of adolescence. All selected participants (n = 1,581) were cannabis‐naïve at age 14. Those reporting any cannabis use (out of six ordinal use levels) by age 16 were included in the outcome group (N = 365, males n = 207). Cannabis‐naïve participants at age 14 and 16 were included in the comparison group (N = 1,216, males n = 538). Psychosocial, brain and genetic features were measured at age 14 prior to any exposure. Cross‐validated regularized logistic regressions for each use level by sex were used to perform feature selection and obtain prediction error statistics on independent observations. Predictors were probed for sex‐ and drug‐specificity using post‐hoc logistic regressions. Models reliably predicted use as indicated by satisfactory prediction error statistics, and contained psychosocial features common to both sexes. However, males and females exhibited distinct brain predictors that failed to predict use in the opposite sex or predict binge drinking in independent samples of same‐sex participants. Collapsed across sex, genetic variation on catecholamine and opioid receptors marginally predicted use. Using machine learning techniques applied to a large multimodal dataset, we identified a risk profile containing psychosocial and sex‐specific brain prognostic markers, which were likely to precede and influence cannabis initiation. [ABSTRACT FROM AUTHOR]

Rates of cannabis use among adolescents are high, and are increasing concurrent with changes in the legal status of marijuana and societal attitudes regarding its use. Recreational cannabis use is understudied, especially in the adolescent period when neural maturation may make users particularly vulnerable to the effects of A-9-tetrahydrocannabinol (THC) on brain structure. In the current study, we used voxel-based morphometry to compare gray matter volume (GMV) in forty-six 14-year-old human adolescents (males and females) with just one or two instances of cannabis use and carefully matched THC-naive controls. We identified extensive regions in the bilateral medial temporal lobes as well as the bilateral posterior cingulate, lingual gyri, and cerebellum that showed greater GMV in the cannabis users. Analysis of longitudinal data confirmed that GMV differences were unlikely to precede cannabis use. GMV in the temporal regions was associated with contemporaneous performance on the Perceptual Reasoning Index and with future generalized anxiety symptoms in the cannabis users. The distribution of GMV effects mapped onto biomarkers of the endogenous cannabinoid system providing insight into possible mechanisms for these effects. [ABSTRACT FROM AUTHOR]

Kant's 'principle of right' claims that individual freedom can only be realized through the construction of law. As "punishment is a categorical imperative" (6: 331) failure to punish those who violate public laws constitutes a grave wrong. Yet, in the 'right of nations' Kant claims that amnesties must be granted when wrongdoing occurs between states (6: 349). How can it be that within a civil society amnesty should not be granted but that among nations it should be? There has been little attempt to reconcile Kant's endorsement of amnesty with the principle of right. My first task is to show the conditions under which the use of amnesties can be justified. However, the second aim is to show that granting states a 'right to secede' from the global civil condition renders amnesties a tool of impunity. If states are permitted to forgo their commitment to multilateral treaties, then international prosecutions cannot be carried out. I conclude by showing that the right to secede is incompatible with the principle of right. From the perspective of transitional justice, rejecting the right to secede is desirable as it shows that non-consequentialist considerations must bear on the design of domestic and foreign policy. [ABSTRACT FROM AUTHOR]

Objective: Alcohol, tobacco and cannabis use in adolescence is associated with adverse outcomes. Characterizing adolescent substance misusers, however, is difficult due to the wide range of risk and protective factors linked to substance use. The aim of the present study was to examine the role of the Individual, Family, School, Peer, and Social Environment on alcohol (lifetime and risky), tobacco (risky only), and cannabis use (lifetime and riskiness). Method: Data were analyzed from a national sample of 5,680 adolescents, capturing substance use behavior alongside risk and protective factors across Individual, Family, School, Peer and Social domains. We applied a sophisticated machine learning classifier to develop models of alcohol, tobacco and cannabis initiation and misuse. Results: We found highly accurate (area under curve of receiver-operator-characteristic for out-of-sample performance was > .88) and replicable (over multiple iterations and in comparison with permuted outcomes) dissociable psychosocial profiles of alcohol, tobacco and cannabis use. Alongside common predictors (peer relations and externalizing behavior), dissociable risk and resilience factors were observed. Adolescent profiles of alcohol use were distinguished by the contribution of multiple domains. In contrast, tobacco use was characterized by a small number of individual variables, including female gender and poor perceived academic position. Cannabis use was differentiated by the distinct contribution of Individual risk factors, in particular male gender and feelings of anger. Differential associations were also evident, with the strength and direction of association differing substantially across substances. Conclusion: This study indicates that the relationship between the environment and substance use is more complex than previously thought. [ABSTRACT FROM AUTHOR]

Background: Impulsivity, broadly characterized as the tendency to act prematurely without foresight, is linked to alcohol misuse in college students. However, impulsivity is a multidimensional construct and different subdomains likely underlie different patterns of alcohol misuse. Here, we quantified the association between alcohol intoxication frequency and alcohol consumption frequency and choice, action, cognitive, and trait domains of impulsivity. Methods: University student drinkers (n = 106) completed a battery of demographic and alcoholrelated items, as well as self-report and task-based measures indexing different facets of impulsivity. Two orthogonal latent factors, intoxication frequency and alcohol consumption frequency, were generated. Their validity was demonstrated with respect to adverse consequences of alcohol use. Machine learning with penalized regression and feature selection was then utilized to predict intoxication and alcohol consumption frequency using all impulsivity subdomains. Out-of-sample validation was used to quantify model performance. Results: Impulsivity measures alone were significant predictors of intoxication frequency, but not consumption frequency. Propensity for increased intoxication frequency was characterized by increased trait impulsivity, including the Disinhibition subscale of the Sensation Seeking Scale, Attentional and Non-planning subscales of the Barratt Impulsiveness Scale, increased task-based cognitive impulsivity (response time variability), and increased choice impulsivity (steeper delay discounting on a delay discounting questionnaire). A model combining impulsivity domains with other risk factors (gender; nicotine, cannabis, and other drug use; executive functioning; and learning processes) was also significant but did not outperform the model comprising of impulsivity alone. Conclusions: Intoxication frequency, but not consumption frequency, was characterized by a number of impulsivity subdomains. [ABSTRACT FROM AUTHOR]

Despite abundant research into the neurobiology of mental disorders, to date neurobiological insights have had very little impact on psychiatric diagnosis or treatment. In this review, we contend that the search for neuroimaging biomarkers--neuromarkers--of mental disorders is a highly promising avenue toward improved psychiatric healthcare. However, many of the traditional tools used for psychiatric neuroimaging are inadequate for the identification of neuromarkers. Specifically, we highlight the need for larger samples and for multivariate analysis. Approaches such as machine learning are likely to be beneficial for interrogating high-dimensional neuroimaging data. We suggest that broad, population-based study designs will be important for developing neuromarkers of mental disorders, and will facilitate a move away from a phenomenological definition of mental disorder categories and toward psychiatric nosology based on biological evidence. We provide an outline of how the development of neuromarkers should occur, emphasizing the need for tests of external and construct validity, and for collaborative research efforts. Finally, we highlight some concerns regarding the development, and use of, neuromarkers in psychiatric healthcare. [ABSTRACT FROM AUTHOR]

Event-related potentials (ERPs) show promise to be objective indicators of cognitive functioning. The aim of the study was to examine if ERPs recorded during an oddball task would predict cognitive functioning and information processing speed in Multiple Sclerosis (MS) patients and controls at the individual level. Seventy-eight participants (35 MS patients, 43 healthy age-matched controls) completed visual and auditory 2- and 3-stimulus oddball tasks with 128-channel EEG, and a neuropsychological battery, at baseline (month 0) and at Months 13 and 26. ERPs from 0 to 700 ms and across the whole scalp were transformed into 1728 individual spatio-temporal datapoints per participant. A machine learning method that included penalized linear regression used the entire spatio-temporal ERP to predict composite scores of both cognitive functioning and processing speed at baseline (month 0), and months 13 and 26. The results showed ERPs during the visual oddball tasks could predict cognitive functioning and information processing speed at baseline and a year later in a sample of MS patients and healthy controls. In contrast, ERPs during auditory tasks were not predictive of cognitive performance. These objective neurophysiological indicators of cognitive functioning and processing speed, and machine learning methods that can interrogate high-dimensional data, show promise in outcome prediction. [ABSTRACT FROM AUTHOR]

Abstract: Many plant species have pollination and seed dispersal systems and evolutionary histories that have produced strong genetic structuring. These genetic patterns may be consistent with expectations following recent anthropogenic fragmentation, making it difficult to detect fragmentation effects if no prefragmentation genetic data are available. We used microsatellite markers to investigate whether severe habitat fragmentation may have affected the structure and diversity of populations of the endangered Australian bird‐pollinated shrub Grevillea caleyi R.Br., by comparing current patterns of genetic structure and diversity with those of the closely related G. longifolia R.Br. that has a similar life history but has not experienced anthropogenic fragmentation. Grevillea caleyi and G. longifolia showed similar and substantial population subdivision at all spatial levels (global F′ST = 0.615 and 0.454; Sp = 0.039 and 0.066), marked isolation by distance and large heterozygous deficiencies. These characteristics suggest long‐term effects of inbreeding in self‐compatible species that have poor seed dispersal, limited connectivity via pollen flow and undergo population bottlenecks because of periodic fires. Highly structured allele size distributions, most notably in G. caleyi, imply historical processes of drift and mutation were important in isolated subpopulations. Genetic diversity did not vary with population size but was lower in more isolated populations for both species. Through this comparison, we reject the hypothesis that anthropogenic fragmentation has impacted substantially on the genetic composition or structure of G. caleyi populations. Our results suggest that highly self‐compatible species with limited dispersal may be relatively resilient to the genetic changes predicted to follow habitat fragmentation. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to examine symptom profiles of people diagnosed with attention‐deficit/hyperactivity disorder (ADHD) and/or anxiety (ANX) in order to determine the validity of widely used ADHD and ANX rating scales for differential diagnostic use and to develop modified measures that take symptom overlap into account. Design: A cross‐sectional design was used to assess differences in rating scale scores between clinical (n = 52) and control (n = 74) samples as well as differences among subgroups of the clinical sample (22 ADHD; 16 ADHD + ANX; 14 ANX). Method: Participants completed an online questionnaire where they responded to the Conners Adult ADHD Rating Scale (CAARS; Conners, Erhardt, & Sparrow, ) and State Trait Anxiety Inventory scales (STAI; Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, ). Results: Results showed that the CAARS and STAI had limited sensitivity and specificity and may lack in ability to differentially diagnose ADHD and/or ANX. Cluster analysis was used to guide the proposal of modifications for the two scales, which were to use inattentive items only for the CAARS and to exclude state ANX‐present items on the STAI for use in differential diagnosis. Further parametric analysis supported these proposed modifications. Conclusions: Clinicians should be made aware of the limitations of the CAARS and STAI scales in terms of specificity, when used to inform differential diagnosis of ADHD and ANX. Further analysis on the psychometric properties of these modified scales is needed in order to confirm that they are valid and reliable scales. Practitioner points: Clinical implications It is possible that widely used self‐report rating scales are not valid for use in the context of assessing adult ADHD when ANX is present. Clinicians should take alternative approaches to measuring ADHD symptoms in the context of ANX. Findings of the present study suggest the use of inattentive items only for the CAARS and to exclude state ANX‐present items on the STAI for differential diagnostic use.Limitations of the study The sample sizes of the clinical subgroups were relatively small. Diagnoses were not confirmed using a semi‐structured clinical interview. Alternative cluster approaches (e.g., two‐step clustering using larger samples) would provide further insight. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the neural correlates of psychotic-like experiences in youths during tasks involving inhibitory control, reward anticipation, and emotion processing. A secondary aim was to test whether these neuro-functional correlates of risk were predictive of psychotic symptoms 2 years later. Method: Functional imaging responses to three paradigms—the stop-signal, monetary incentive delay, and faces tasks—were collected in youths at age 14, as part of the IMAGEN study. At baseline, youths from London and Dublin siteswere assessed on psychotic-like experiences, and those reporting significant experiences were compared with matched control subjects. Significant brain activity differences between the groups were used to predict, with cross-validation, the presence of psychotic symptoms in the context of mood fluctuation at age 16, assessed in the full sample. These prediction analyses were conducted with the London-Dublinsubsample (N=246) and the full sample (N=1,196). Results: Relative to control subjects, youths reporting psychotic-like experiences showed increased hippocampus/amygdala activity during processing of neutral faces and reduced dorsolateral prefrontal activity during failed inhibition.The most prominent regional difference for classifying 16-year-olds with mood fluctuation and psychotic symptoms relative to the control groups (those with mood fluctuations but no psychotic symptoms and those with no mood symptoms) was hyperactivation of the hippocampus/amygdala, when controlling for baseline psychotic-like experiences and cannabis use. Conclusions: The results stress the importance of the limbicnetwork's increased response to neutral facial stimuli as a marker of the extended psychosis phenotype. These findings might help to guide early intervention strategies for at-risk youths. [ABSTRACT FROM AUTHOR]

Background and Aims Dysfunction in brain regions underlying impulse control, reward processing and executive function have been associated previously with adolescent alcohol misuse. However, identifying pre-existing neurobiological risk factors, as distinct from changes arising from early alcohol-use, is difficult. Here, we outline how neuroimaging data can identify the neural predictors of adolescent alcohol-use initiation and misuse by using prospective longitudinal studies to follow initially alcohol-naive individuals over time and by neuroimaging adolescents with inherited risk factors for alcohol misuse. Method A comprehensive narrative of the literature regarding neuroimaging studies published between 2010 and 2016 focusing on predictors of adolescent alcohol use initiation and misuse. Findings Prospective, longitudinal neuroimaging studies have identified pre-existing differences between adolescents who remained alcohol-naive and those who transitioned subsequently to alcohol use. Both functional and structural grey matter differences were observed in temporal and frontal regions, including reduced brain activity in the superior frontal gyrus and temporal lobe, and thinner temporal cortices of future alcohol users. Interactions between brain function and genetic predispositions have been identified, including significant association found between the Ras protein-specific guanine nucleotide releasing factor 2 ( RASGRF2) gene and reward-related striatal functioning. Conclusions Neuroimaging predictors of alcohol use have shown modest utility to date. Future research should use out-of-sample performance as a quantitative measure of a predictor's utility. Neuroimaging data should be combined across multiple modalities, including structural information such as volumetrics and cortical thickness, in conjunction with white-matter tractography. A number of relevant neurocognitive systems should be assayed; particularly, inhibitory control, reward processing and executive functioning. Combining a rich magnetic resonance imaging data set could permit the generation of neuroimaging risk scores, which could potentially yield targeted interventions. [ABSTRACT FROM AUTHOR]

Background: Despite calls for integration of neurobiological methods into research on youth resilience (high competence despite high adversity), we know little about structural brain correlates of resilient functioning. The aim of the current study was to test for brain regions uniquely associated with positive functioning in the context of adversity, using detailed phenotypic classification. Methods: 1,870 European adolescents (Mage = 14.56 years, SDage = 0.44 years, 51.5% female) underwent MRI scanning and completed behavioral and psychological measures of stressful life events, academic competence, social competence, rule-abiding conduct, personality, and alcohol use. Results: The interaction of competence and adversity identified two regions centered on the right middle and superior frontal gyri; grey matter volumes in these regions were larger in adolescents experiencing adversity who showed positive adaptation. Differences in these regions among competence/adversity subgroups were maintained after controlling for several covariates and were robust to alternative operationalization decisions for key constructs. Conclusions: We demonstrate structural brain correlates of adolescent resilience, and suggest that right prefrontal structures are implicated in adaptive functioning for youth who have experienced adversity. [ABSTRACT FROM AUTHOR]

The subject matter of neuroscience research is complex, and synthesising the wealth of data from this research to better understand mental processes is challenging. A useful strategy, therefore, may be to distinguish explicitly between the causal effects of the environment on behaviour (i.e. functional analyses) and the mental processes that mediate these effects (i.e. cognitive analyses). In this article, we describe how the functional-cognitive (F-C) framework can accelerate cognitive neuroscience and also advance a functional treatment of brain activity. We first highlight that cognitive neuroscience can particularly benefit from the F-C approach by providing an alternative to the problematic practice of reducing cognitive constructs to behavioural and/or neural proxies. Next, we outline how functional (behaviour-environment) relations can serve as a bridge between cognitive and neural processes by restoring mental constructs to their original role as heuristic tools. Finally, we give some examples of how both cognitive neuroscience and traditional functional approaches can mutually benefit from the F-C framework. [ABSTRACT FROM AUTHOR]

Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis. [ABSTRACT FROM AUTHOR]