Effects of perceptual redundancy, conceptual redundancy and self-relatedness on categorical responses.

A redundancy gain occurs when perceptually identical stimuli are presented together, resulting in quicker categorization of these paired stimuli than lone stimuli. Similar effects have been reported for paired stimuli within the same conceptual category, particularly if the category is self-related. We recruited 528 individuals across three related studies to investigate whether, during perceptual and conceptual redundancy, such self-bias effects on foreground stimuli are modulated by natural versus urban backgrounds. Here, we highlight our observations pertaining to perceptual and conceptual redundancy effects of the foreground stimuli. In our first experiment, response options were randomised per trial. Results showed reaction time gains for perceptually identical stimuli, but this advantage was not modulated by self/other categorization. However, slower reaction times were observed for conceptually-related stimulus pairs and were influenced by self/other categorization. The second experiment replicated the methods of earlier studies of redundancy and observed comparable results to Experiment 1: a perceptual redundancy gain unmodulated by self/other categorization, yet for conceptual redundancy, no gain/cost but effects of self/other categorization. In the third experiment, self/other categories were substituted with arbitrary A/B categories: Once more, there was a perceptual redundancy gain and no conceptual redundancy gain. Notably, A/B categorisation produced effects equivalent to self/other categorisation. Overall, these findings challenge previous research on the facilitated early processing of conceptually-related stimuli and suggest that self-relatedness may not exert a unique effect on stimulus processing beyond attentional and response preferences during categorization. Our study motivates further research to understand conceptual categorization and redundancy gain effects.

The impact of attention bias modification training on behavioral and physiological responses.

Attention bias modification training aims to alter attentional deployment to symptom-relevant emotionally salient stimuli. Such training has therapeutic applications in the management of disorders including anxiety, depression, addiction and chronic pain. In emotional reactions, attentional biases interact with autonomically-mediated changes in bodily arousal putatively underpinning affective feeling states. Here we examined the impact of attention bias modification training on behavioral and autonomic reactivity. Fifty-eight participants were divided into two groups. A training group (TR) received attention bias modification training to enhance attention to pleasant visual information, while a control group (CT) performed a procedure that did not modify attentional bias. After training, participants performed an evaluation task in which pairs of emotional and neutral images (unpleasant-neutral, pleasant-neutral, neutral-neutral) were presented, while behavioral (eye movements) and autonomic (skin conductance; heart rate) responses were recorded. At the behavioral level, trained participants were faster to orientate attention to pleasant images, and slower to orientate to unpleasant images. At the autonomic level, trained participants showed attenuated skin conductance responses to unpleasant images, while stronger skin conductance responses were generally associated with higher anxiety. These data argue for the use of attentional training to address both the attentional and the physiological sides of emotional responses, appropriate for anxious and depressive symptomatology, characterized by atypical attentional deployment and autonomic reactivity.

The Human Affectome.

Over the last decades, theoretical perspectives in the interdisciplinary field of the affective sciences have proliferated rather than converged due to differing assumptions about what human affective phenomena are and how they work. These metaphysical and mechanistic assumptions, shaped by academic context and values, have dictated affective constructs and operationalizations. However, an assumption about the purpose of affective phenomena can guide us to a common set of metaphysical and mechanistic assumptions. In this capstone paper, we home in on a nested teleological principle for human affective phenomena in order to synthesize metaphysical and mechanistic assumptions. Under this framework, human affective phenomena can collectively be considered algorithms that either adjust based on the human comfort zone (affective concerns) or monitor those adaptive processes (affective features). This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope the Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research.

High ventilation breathwork practices: An overview of their effects, mechanisms, and considerations for clinical applications.

High Ventilation Breathwork (HVB) refers to practices employing specific volitional manipulation of breathing, with a long history of use to relieve various forms of psychological distress. This paper seeks to offer a consolidative insight into potential clinical application of HVB as a treatment of psychiatric disorders. We thus review the characteristic phenomenological and neurophysiological effects of these practices to inform their mechanism of therapeutic action, safety profiles and future clinical applications. Clinical observations and data from neurophysiological studies indicate that HVB is associated with extraordinary changes in subjective experience, as well as with profound effects on central and autonomic nervous systems functions through modulation of neurometabolic parameters and interoceptive sensory systems. This growing evidence base may guide how the phenomenological effects of HVB can be understood, and potentially harnessed in the context of such volitional perturbation of psychophysiological state. Reports of putative beneficial effects for trauma-related, affective, and somatic disorders invite further research to obtain detailed mechanistic knowledge, and rigorous clinical testing of these potential therapeutic uses.

Evidence that pupil dilation and cardiac afferent signalling differentially impact the processing of emotional intensity and racial bias.

Interoceptive cardiac arousal signals (e.g., from baroreceptor firing at ventricular systole compared to diastole) have been found to enhance perception of fearful versus neutral faces. They have also been found to amplify racially biased misidentification of tools as weapons when preceded by facial images of Black versus White individuals. Since pupil size is strongly coupled to arousal, we tested if experimental manipulation of pupil size influences fear processing in emotional judgement and racial bias tasks involving measurement of cardiac signals. In a sample of 22 non-clinical participants in an emotional intensity judgement task, pupil size did not affect emotional intensity ratings. Nor did it interact with differential effects of cardiac systole versus diastole on intensity judgements of fearful and neutral faces, replicated here. In a sample of 25 non-clinical participants in a weapons identification task, larger pupil size resulted in faster response times and lower accuracy when identifying tools and weapons. However, pupil size did not interact with weapon versus tool identification, race of prime, or cardiac timing. We nevertheless replicated the observed increase in racially biased misidentification of tools as weapons following Black face primes presented at cardiac systole. Together our findings indicate that pupil dilation does not directly influence the processing of fear cues or perceived threat (as in racial bias) yet affects task performance by decreasing response times and accuracy. These findings contrast with the established effect of cardiac arousal signals on threat processing and may help focus interventions to mitigate related decision errors in high-pressure occupations.

Elevated representational similarity of voluntary action and inhibition in Tourette syndrome.

Many people with Tourette syndrome are able to volitionally suppress tics, under certain circumstances. To understand better the neural mechanisms that underlie this ability, we used functional magnetic resonance neuroimaging to track regional brain activity during performance of an intentional inhibition task. On some trials, Tourette syndrome and comparison participants internally chose to make or withhold a motor action (a button press), while on other trials, they followed 'Go' and 'NoGo' instructions to make or withhold the same action. Using representational similarity analysis, a functional magnetic resonance neuroimaging multivariate pattern analysis technique, we assessed how Tourette syndrome and comparison participants differed in neural activity when choosing to make or to withhold an action, relative to externally cued responses on Go and NoGo trials. Analyses were pre-registered, and the data and code are publicly available. We considered similarity of action representations within regions implicated as critical to motor action release or inhibition and to symptom expression in Tourette syndrome, namely the pre-supplementary motor area, inferior frontal gyrus, insula, caudate nucleus and primary motor cortex. Strikingly, in the Tourette syndrome compared to the comparison group, neural activity within the pre-supplementary motor area displayed greater representational similarity across all action types. Within the pre-supplementary motor area, there was lower response-specific differentiation of activity relating to action and inhibition plans and to internally chosen and externally cued actions, implicating the region as a functional nexus in the symptomatology of Tourette syndrome. Correspondingly, patients with Tourette syndrome may experience volitional tic suppression as an effortful and tiring process because, at the top of the putative motor decision hierarchy, activity within the population of neurons facilitating action is overly similar to activity within the population of neurons promoting inhibition. However, not all pre-supplementary motor area group differences survived correction for multiple comparisons. Group differences in representational similarity were also present in the primary motor cortex. Here, representations of internally chosen and externally cued inhibition were more differentiated in the Tourette syndrome group than in the comparison group, potentially a consequence of a weaker voluntary capacity earlier in the motor hierarchy to suppress actions proactively. Tic severity and premonitory sensations correlated with primary motor cortex and caudate nucleus representational similarity, but these effects did not survive correction for multiple comparisons. In summary, more rigid pre-supplementary motor area neural coding across action categories may constitute a central feature of Tourette syndrome, which can account for patients' experience of 'unvoluntary' tics and effortful tic suppression.

Impaired cardiac modulation in patients with functional seizures: Results from a face intensity judgment task.

OBJECTIVE: Although interoceptive abnormality in patients with functional seizure (FSs) has been demonstrated using explicit tasks, implicit measurements of interoception such as the effect of interoception on perceptual brain processes have not been investigated. It has been shown that perception is normally modulated by interoceptive signals related to the different phases (systole vs diastole) of the cardiac cycle (cardiac modulation effect). Given our previous findings using explicit measures of interoception, we hypothesized that cardiac modulation would be impaired in FSs. METHODS: Thirty-two patients with FSs and 30 age- and sex-matched non-clinical individuals conducted a face intensity judgment task, in which their intensity rating when fearful or neutral faces was presented was compared between systolic and diastolic phases. They also conducted the heartbeat discrimination task as a measure of their capacity to integrate both interoceptive and exteroceptive information. RESULTS: Patients with FSs had impaired cardiac modulation of the perception of neutral faces (corrected p = .044). Individual differences in the heartbeat discrimination task predicted the degree to which cardiac modulation occurred across the whole group (p = .028). This cardiac modulation effect was significantly associated with seizure severity (p = .021). Regardless of cardiac phase, patients rated fearful facial expressions as less intense compared to control participants (p = .006). SIGNIFICANCE: These findings highlight impaired implicit cardiac modulation effects in patients with FSs. This reflects interoceptive dysfunction in patients with FSs, and an inability of the brain to integrate interoceptive signaling with perceptual processing. This may have implications for our understanding of the pathophysiology in FSs and inform novel diagnostic approaches.

Changes in the heartbeat-evoked potential are associated with functional seizures.

BACKGROUND: Patients with functional seizures (FS) can experience dissociation (depersonalisation) before their seizures. Depersonalisation reflects disembodiment, which may be related to changes in interoceptive processing. The heartbeat-evoked potential (HEP) is an electroencephalogram (EEG) marker of interoceptive processing. AIM: To assess whether alterations in interoceptive processing indexed by HEP occur prior to FS and compare this with epileptic seizures (ES). METHODS: HEP amplitudes were calculated from EEG during video-EEG monitoring in 25 patients with FS and 19 patients with ES, and were compared between interictal and preictal states. HEP amplitude difference was calculated as preictal HEP amplitude minus interictal HEP amplitude. A receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of HEP amplitude difference in discriminating FS from ES. RESULTS: The FS group demonstrated a significant reduction in HEP amplitude between interictal and preictal states at F8 (effect size rB=0.612, false discovery rate (FDR)-corrected q=0.030) and C4 (rB=0.600, FDR-corrected q=0.035). No differences in HEP amplitude were found between states in the ES group. Between diagnostic groups, HEP amplitude difference differed between the FS and ES groups at F8 (rB=0.423, FDR-corrected q=0.085) and C4 (rB=0.457, FDR-corrected q=0.085). Using HEP amplitude difference at frontal and central electrodes plus sex, we found that the ROC curve demonstrated an area under the curve of 0.893, with sensitivity=0.840 and specificity=0.842. CONCLUSION: Our data support the notion that aberrant interoception occurs prior to FS. Changes in HEP amplitude may reflect a neurophysiological biomarker of FS and may have diagnostic utility in differentiating FS and ES.

Beyond the symptom: the biology of fatigue.

A workshop titled "Beyond the Symptom: The Biology of Fatigue" was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a list of promising directions for future research on this topic. We do not attempt to provide a comprehensive review of the state of our understanding of fatigue, nor to provide a comprehensive reprise of the many excellent presentations. Rather, our goal is to highlight key advances and to focus on questions and future approaches to answering them.

Cardiac interoception in patients accessing secondary mental health services: A transdiagnostic study.

BACKGROUND: Abnormalities in the regulation of physiological arousal and interoceptive processing are implicated in the expression and maintenance of specific psychiatric conditions and symptoms. We undertook a cross-sectional characterisation of patients accessing secondary mental health services, recording measures relating to cardiac physiology and interoception, to understand how physiological state and interoceptive ability relate transdiagnostically to affective symptoms. METHODS: Participants were patients (n = 258) and a non-clinical comparison group (n = 67). Clinical diagnoses spanned affective disorders, complex personality presentations and psychoses. We first tested for differences between patient and non-clinical participants in terms of cardiac physiology and interoceptive ability, considering interoceptive tasks and a self-report measure. We then tested for correlations between cardiac and interoceptive measures and affective symptoms. Lastly, we explored group differences across recorded clinical diagnoses. RESULTS: Patients exhibited lower performance accuracy and confidence in heartbeat discrimination and lower heartbeat tracking confidence relative to comparisons. In patients, greater anxiety and depression predicted greater self-reported interoceptive sensibility and a greater mismatch between performance accuracy and sensibility. This effect was not observed in comparison participants. Significant differences between patient groups were observed for heart rate variability (HRV) although post hoc differences were not significant after correction for multiple comparisons. Finally, accuracy in heartbeat tracking was significantly lower in schizophrenia compared to other diagnostic groups. CONCLUSIONS: The multilevel characterisation presented here identified certain physiological and interoceptive differences associated with psychiatric symptoms and diagnoses. The clinical stratification and therapeutic targeting of interoceptive mechanisms is therefore of potential value in treating certain psychiatric conditions.

Variant connective tissue (joint hypermobility) and its relevance to depression and anxiety in adolescents: a cohort-based case-control study.

OBJECTIVE: To test whether variant connective tissue structure, as indicated by the presence of joint hypermobility, poses a developmental risk for mood disorders in adolescence. DESIGN: Cohort-based case-control study. SETTING: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were interrogated. PARTICIPANTS: 6105 children of the ALSPAC cohort at age 14 years old, of whom 3803 also were assessed when aged 18 years. MAIN OUTCOME MEASURES: In a risk analysis, we examined the relationship between generalised joint hypermobility (GJH) at age 14 years with psychiatric symptoms at age 18 years. In an association analysis, we examined the relationship between presence of symptomatic joint hypermobility syndrome (JHS) and International Classification of Diseases-10 indication of depression and anxiety (Clinical Interview Schedule Revised (CIS-R), Anxiety Sensitivity Index) at age 18 years. RESULTS: GJH was more common in females (n=856, 28%) compared with males (n=319, 11%; OR: 3.20 (95% CI: 2.78 to 3.68); p<0.001). In males, GJH at age 14 years was associated with depression at 18 years (OR: 2.10 (95% CI: 1.17 to 3.76); p=0.013). An index of basal physiological arousal, elevated resting heart rate, mediated this effect. Across genders, the diagnosis of JHS at age 18 years was associated with the presence of depressive disorder (adjusted OR: 3.53 (95% CI: 1.67 to 7.40); p=0.001), anxiety disorder (adjusted OR: 3.14 (95% CI: 1.52 to 6.46); p=0.002), level of anxiety (B=8.08, t(3278)=3.95; p<0.001) and degree of psychiatric symptomatology (B=5.89, t(3442)=5.50; p<0.001). CONCLUSIONS: Variant collagen, indexed by joint hypermobility, is linked to the emergence of depression and anxiety in adolescence, an effect mediated by autonomic factors in males. Recognition of this association may motivate further evaluation, screening and interventions to mitigate development of psychiatric disorders and improve health outcomes.

The relationship between interoception and agency and its modulation by heartbeats: an exploratory study.

Interoception, the sense of the internal physiological state of the body, theoretically underpins aspects of self-representation. Experimental studies link feelings of body ownership to interoceptive perception, yet few studies have tested for association between the sense of agency and interoceptive processing. Here, we combined an intentional binding paradigm with cardiac measures of interoceptive processing (behavioural performance on a heartbeat discrimination task, and effects of timing within the cardiac cycle) in twenty-six non-clinical participants as an exploratory study. We found performance accuracy on the heartbeat discrimination task correlated positively with the intentional binding effect, an index of sense of agency (ß = 0.832, p = 0.005), even after controlling for effects of age, sex, educational level, heart rate, heart rate variability and time accuracy. The intentional binding effect was enhanced during cardiac systole (compared to diastole) in individuals with greater heartbeat discrimination accuracy (ß = 0.640, p = 0.047). These findings support the proposal that interoception contributes to mechanisms underlying the emergence of sense of agency.

Divergent Conceptualization of Embodied Emotions in the English and Chinese Languages.

Traditional cognitive linguistic theories acknowledge that human emotions are embodied, yet they fail to distinguish the dimensions that reflect the direction of neural signaling between the brain and body. Differences exist across languages and cultures in whether embodied emotions are conceptualized as afferent (feelings from the body) or efferent (enacted through the body). This important distinction has been neglected in academic discourse, arguably as a consequence of the 'lexical approach', and the dominance within the affective psychology of the cognitive and semantic models that overlook the role of interoception as an essential component of affective experience. Empirical and theoretical advances in human neuroscience are driving a reappraisal of the relationships between the mind, brain and body, with particular relevance to emotions. Allostatic (predictive) control of the internal bodily states is considered fundamental to the experience of emotions enacted through interoceptive sensory feelings and through the evoked physiological and physical actions mediated through efferent neural pathways. Embodied emotion concepts encompass these categorized outcomes of bidirectional brain-body interactions yet can be differentiated further into afferent or interoceptive and efferent or autonomic processes. Between languages, a comparison of emotion words indicates the dominance of afferent or interoceptive processes in how embodied emotions are conceptualized in Chinese, while efferent or autonomic processes feature more commonly in English. Correspondingly, in linguistic expressions of emotion, Chinese-speaking people are biased toward being more receptive, reflective, and adaptive, whereas native English speakers may tend to be more reactive, proactive, and interactive. Arguably, these distinct conceptual models of emotions may shape the perceived divergent values and 'national character' of Chinese- and English-speaking cultures.

Spelling Errors in Brief Computer-Mediated Texts Implicitly Lead to Linearly Additive Penalties in Trustworthiness.

Background: Spelling errors in documents lead to reduced trustworthiness, but the mechanism for weighing the psychological assessment (i.e., integrative versus dichotomous) has not been elucidated. We instructed participants to rate content of texts, revealing that their implicit trustworthiness judgments show marginal differences specifically caused by spelling errors. Methods: An online experiment with 100 English-speaking participants were asked to rate 27 short text excerpts (∼100 words) about multiple sclerosis in the format of unmoderated health forum posts. In a counterbalanced design, some excerpts had no typographic errors, some had two errors, and some had five errors. Each participant rated nine paragraphs with a counterbalanced mixture of zero, two or five errors. A linear mixed effects model (LME) was assessed with error number as a fixed effect and participants as a random effect. Results: Using an unnumbered scale with anchors of "completely untrustworthy" (left) and "completely trustworthy" (right) recorded as 0 to 100, two spelling errors resulted in a penalty to trustworthiness of 5.91 ± 1.70 (robust standard error) compared to the reference excerpts with zero errors, while the penalty for five errors was 13.5 ± 2.47; all three conditions were significantly different from each other (P < 0.001). Conclusion: Participants who rated information about multiple sclerosis in a context mimicking an online health forum implicitly assigned typographic errors nearly linearly additive trustworthiness penalties. This contravenes any dichotomous heuristic or local ceiling effect on trustworthiness penalties for these numbers of typographic errors. It supports an integrative model for psychological judgments of trustworthiness.

Hypermobility in patients with functional seizures: Toward a pathobiological understanding of complex conditions.

BACKGROUND: Functional seizures (FS), otherwise known as psychogenic nonepileptic seizures (PNES), are a common symptom presenting to neurology and epilepsy clinics. There is a pressing need for further research to understand the neurobiology of FS to develop mechanistically targeted treatments. Joint hypermobility is an expression of variation in connective tissue structure along a spectrum, and it has received increasing attention in functional neurological disorders, but there is lack of evidence of its relevance in FS. METHODS: In the present study, forty-two patients with FS and a non-clinical comparison group of 34 age/sex-matched controls were recruited. Joint hypermobility of all participants was quantified using the Beighton scale. RESULTS: In our sample, 24 (57%) patients with FS, and 7 (21%) of the comparison group met criteria for joint hypermobility (p = 0.002). Our statistical model revealed that patients with FS showed a significant degree of hypermobility compared to the comparison group (odds ratio = 11.1; Confidence interval: 2.1-78.0, p = 0.008), even after controlling age, sex, anxiety, and depression. CONCLUSION: We found a significant association between FS and joint hypermobility, which was independent of anxiety and depression.

A single oral dose of citalopram increases interoceptive insight in healthy volunteers.

RATIONALE: Interoception is the signalling, perception, and interpretation of internal physiological states. Many mental disorders associated with changes of interoception, including depressive and anxiety disorders, are treated with selective serotonin reuptake inhibitors (SSRIs). However, the causative link between SSRIs and interoception is not yet clear. OBJECTIVES: To ascertain the causal effect of acute changes of serotonin levels on cardiac interoception. METHODS: Using a within-participant placebo-controlled design, forty-seven healthy human volunteers (31 female, 16 male) were tested on and off a 20 mg oral dose of the commonly prescribed SSRI, citalopram. Participants made judgements on the synchrony between their heartbeat and auditory tones and then expressed confidence in each judgement. We measured three types of interoceptive cognition. RESULTS: Citalopram increased cardiac interoceptive insight, measured as correspondence of self-reported confidence to the likelihood that interoceptive judgements were actually correct. This effect was driven by enhanced confidence for correct interoceptive judgements and was independent of measured cardiac and reported subjective effects of the drug. CONCLUSIONS: An acute change of serotonin levels can increase insight into the reliability of inferences made from cardiac interoceptive sensations.

Cardiac deceleration following positive and negative feedback is influenced by competence-based social status.

Previous studies indicate that neurophysiological signatures of feedback processing might be enhanced when participants are assigned a low-status position. Error commission and negative feedback can evoke responses in the peripheral (autonomic) nervous system including heart rate deceleration. We conducted an exploratory study to investigate whether such activity can be modulated by the participant's social status in a competence-based hierarchy. Participants were engaged in a cooperative time estimation task with two same-gender confederates. On each trial, they were provided with positive or negative feedback depending on their time estimation performance. Their social status varied during the task, so that they were either at the top (high-status) or at the bottom (low-status) of the hierarchy in different blocks. Results showed that cardiac deceleration was significantly modulated by feedback valence in the high-status but not in the low-status condition. We interpret this result as an increased activation of the performance monitoring system elicited by the desire to maintain a high-status position in an unstable hierarchy. In this vein, negative feedback might be processed as an aversive stimulus that signals a threat to the acquired status.

Cognition, emotion, and the central autonomic network.

The demands of both mental and physical activity are integrated with the dynamic control of internal bodily states. The set of neural interactions that supports autonomic regulation extends beyond afferent-efferent homeostatic reflexes (interoceptive feedback, autonomic action) to encompass allostatic policies reflecting more abstract and predictive mental representations, often accessed as conscious thoughts and feelings. Historically and heuristically, reason is contrasted with passion, cognition with emotion, and 'cold' with 'hot' cognition. These categories are themselves arbitrary and blurred. Investigations of psychological processes have been generally pursued during states of musculoskeletal quiescence and are thus relatively insensitive to autonomic interaction with attentional, perceptual, mnemonic and decision-making processes. Autonomic psychophysiology has nevertheless highlighted the bidirectional coupling of distinct cognitive domains to the internal states of bodily arousal. More powerfully perhaps, in the context of emotion, autonomically mediated changes in inner bodily physiological states are viewed as intrinsic constituents of the expression of emotions, while their feedback representation is proposed to underpin emotional and motivational feelings. Here, we review the brain systems, encapsulated by the notion of central autonomic network, that provide the interface between cognitive, emotional and autonomic state. These systems span the neuraxis, overlap with the more general governance of behaviour, and represent district levels of proximity to survival-related imperatives. We touch upon the conceptual relevance of prediction and surprise to understanding the integration of cognition and emotion with autonomic control.

The Cardiac Timing Toolbox (CaTT): Testing for physiologically plausible effects of cardiac timing on behaviour.

There is a long history of, and renewed interest in, cardiac timing effects on behaviour and cognition. Cardiac timing effects may be identified by expressing events as a function of their location in the cardiac cycle, and applying circular (i.e. directional) statistics to test cardiac time-behaviour associations. Typically this approach 'stretches' all points in the cardiac cycle equally, but this is not necessarily physiologically valid. Moreover, many tests impose distributional assumptions that are not met by such data. We present a set of statistical techniques robust to this, instantiated within our new Cardiac Timing Toolbox (CaTT) for MATLAB: A physiologically-motivated method of wrapping behaviour to the cardiac cycle; and a set of non-parametric statistical tests that control for common confounds and distributional characteristics of these data. Using a reanalysis of previously published data, we guide readers through analyses using CaTT, aiding researchers in identifying physiologically plausible associations between heart-timing and cognition.

Mega-analysis methods in ENIGMA: The experience of the generalized anxiety disorder working group.

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.