Neurodesk: an accessible, flexible and portable data analysis environment for reproducible neuroimaging.

Neuroimaging research requires purpose-built analysis software, which is challenging to install and may produce different results across computing environments. The community-oriented, open-source Neurodesk platform ( https://www.neurodesk.org/ ) harnesses a comprehensive and growing suite of neuroimaging software containers. Neurodesk includes a browser-accessible virtual desktop, command-line interface and computational notebook compatibility, allowing for accessible, flexible, portable and fully reproducible neuroimaging analysis on personal workstations, high-performance computers and the cloud.

It's who, not what that matters: personal relevance and early face processing.

The faces of our friends and loved ones are among the most pervasive and important social stimuli we encounter in our everyday lives. We employed electroencephalography to investigate the time line of personally relevant face processing and potential interactions with emotional facial expressions by presenting female participants with photographs of their romantic partner, a close friend and a stranger, displaying fearful, happy and neutral facial expressions. Our results revealed elevated activity to the partner's face from 100 ms after stimulus onset as evident in increased amplitudes of P1, early posterior negativity, P3 and late positive component, while there were no effects of emotional expressions and no interactions. Our findings indicate the prominent role of personal relevance in face processing; the time course of effects further suggests that it might not rely solely on the core face processing network but might start even before the stage of structural face encoding. Our results suggest a new direction of research in which face processing models should be expanded to adequately capture the dynamics of the processing of real-life, personally relevant faces.

Neurodesk: An accessible, flexible, and portable data analysis environment for reproducible neuroimaging.

Neuroimaging data analysis often requires purpose-built software, which can be challenging to install and may produce different results across computing environments. Beyond being a roadblock to neuroscientists, these issues of accessibility and portability can hamper the reproducibility of neuroimaging data analysis pipelines. Here, we introduce the Neurodesk platform, which harnesses software containers to support a comprehensive and growing suite of neuroimaging software (https://www.neurodesk.org/). Neurodesk includes a browser-accessible virtual desktop environment and a command line interface, mediating access to containerized neuroimaging software libraries on various computing platforms, including personal and high-performance computers, cloud computing and Jupyter Notebooks. This community-oriented, open-source platform enables a paradigm shift for neuroimaging data analysis, allowing for accessible, flexible, fully reproducible, and portable data analysis pipelines.

Intolerance of uncertainty is associated with heightened responding in the prefrontal cortex during cue-signalled uncertainty of threat.

Heightened responding to uncertain threat is considered a hallmark of anxiety disorder pathology. We sought to determine whether individual differences in self-reported intolerance of uncertainty (IU), a key transdiagnostic dimension in anxiety-related pathology, underlies differential recruitment of neural circuitry during cue-signalled uncertainty of threat (n = 42). In an instructed threat of shock task, cues signalled uncertain threat of shock (50%) or certain safety from shock. Ratings of arousal and valence, skin conductance response (SCR), and functional magnetic resonance imaging were acquired. Overall, participants displayed greater ratings of arousal and negative valence, SCR, and amygdala activation to uncertain threat versus safe cues. IU was not associated with greater arousal ratings, SCR, or amygdala activation to uncertain threat versus safe cues. However, we found that high IU was associated with greater ratings of negative valence and greater activity in the medial prefrontal cortex and dorsomedial rostral prefrontal cortex to uncertain threat versus safe cues. These findings suggest that during cue-signalled uncertainty of threat, individuals high in IU rate uncertain threat as aversive and engage prefrontal cortical regions known to be involved in safety-signalling and conscious threat appraisal. Taken together, these findings highlight the potential of IU in modulating safety-signalling and conscious appraisal mechanisms in situations with cue-signalled uncertainty of threat, which may be relevant to models of anxiety-related pathology.

Rapid Neural Representations of Personally Relevant Faces.

The faces of those most personally relevant to us are our primary source of social information, making their timely perception a priority. Recent research indicates that gender, age and identity of faces can be decoded from EEG/MEG data within 100 ms. Yet, the time course and neural circuitry involved in representing the personal relevance of faces remain unknown. We applied simultaneous EEG-fMRI to examine neural responses to emotional faces of female participants' romantic partners, friends, and a stranger. Combining EEG and fMRI in cross-modal representational similarity analyses, we provide evidence that representations of personal relevance start prior to structural encoding at 100 ms, with correlated representations in visual cortex, but also in prefrontal and midline regions involved in value representation, and monitoring and recall of self-relevant information. Our results add to an emerging body of research that suggests that models of face perception need to be updated to account for rapid detection of personal relevance in cortical circuitry beyond the core face processing network.

Intolerance of uncertainty, and not social anxiety, is associated with compromised extinction of social threat.

Extinction-resistant threat is regarded as a central hallmark of pathological anxiety. However, it remains relatively under-studied in social anxiety. Here we sought to determine whether self-reported trait social anxiety is associated with compromised threat extinction learning and retention. We tested this hypothesis within two separate, socially relevant conditioning studies. In the first experiment, a Selective Extinction Through Cognitive Evaluation (SECE) paradigm was used, which included a cognitive component during the extinction phase, while experiment 2 used a traditional threat extinction paradigm. Skin conductance responses and subjective ratings of anxiety (experiment 1 and 2) and expectancy (experiment 2) were collected across both experiments. The findings of both studies demonstrated no effect of social anxiety on extinction learning or retention. Instead, results from experiment 1 indicated that individual differences in Intolerance of Uncertainty (IU) were associated with the ability to use contextual cues to decrease a conditioned response during SECE. However, during extinction retention, high IU predicted greater generalisation across context cues. Findings of experiment 2 revealed that higher IU was associated with impaired extinction learning and retention. The results from both studies suggest that compromised threat extinction is likely to be a characteristic of high levels of IU and not social anxiety.

Inter-slice leakage and intra-slice aliasing in simultaneous multi-slice echo-planar images.

Simultaneous multi-slice (SMS) imaging is a popular technique for increasing acquisition speed in echo-planar imaging (EPI) fMRI. However, SMS data are prone to motion sensitivity and slice leakage artefacts, which spread signal between simultaneously acquired slices. Relevant to motion sensitivity, artefacts from moving anatomic structures propagate along the phase-encoding (PE) direction. This is particularly relevant for eye movement. As signal from the eye is acquired along with signal from simultaneously excited slices during SMS, there is potential for signal to spread in-plane and between spatially remote slices. After identifying an artefact temporally coinciding with signal fluctuations in the eye and spatially distributed in correspondence with multiband slice acceleration and parallel imaging factors, we conducted a series of small experiments to investigate eye movement artefacts in SMS data and the contribution of PE direction to the invasiveness of these artefacts. Five healthy adult volunteers were scanned during a blinking task using a standard SMS-EPI protocol with posterior-to-anterior (P ≫ A), anterior-to-posterior (A ≫ P) or right-to-left (R ≫ L) PE direction. The intensity of signal fluctuations (artefact severity) was measured at expected artefact positions and control positions. We demonstrated a direct relationship between eye movements and artefact severity across expected artefact regions. Within-brain artefacts were apparent in P ≫ A- and A ≫ P-acquired data but not in R ≫ L data due to the shift in artefact positions. Further research into eye motion artefacts in SMS data is warranted but researchers should exercise caution with SMS protocols. We recommend rigorous piloting of SMS protocols and switching to R ≫ L/L ≫ R PE where feasible.

Selective extinction through cognitive evaluation: Linking emotion regulation and extinction.

The extinction of a previously conditioned response can be modulated through cognitive processes, including feature-based information, and explicit instruction. Here, we introduce a selective extinction through cognitive evaluation (SECE) task in which information is cognitively evaluated on a trial-by-trial basis to ascertain the extinction contingencies. Participants were conditioned to expect an electric shock during the presentation of one of two letters (CS+/CS-). During the SECE task, the letters were presented within words belonging to two categories, one of which indicated safety (COG-_CS+ trials), while risk of shock was maintained for the other category (COG+_CS+ trials). Skin conductance responses indicated that participants reduced their response to COG-_CS+ trials compared to COG+_CS+ trials. Clusters in bilateral insula and anterior cingulate cortex showed activation for COG+_CS+ trials that was reduced for COG-_CS+ trials. A network of brain regions, including left inferior frontal gyrus, and bilateral temporal and parietal cortices showed greater activation for COG-_CS+ versus COG+_CS+ trials. This is consistent with the semantic processing and decision-making necessary to evaluate the trial contingencies. We compared activation in the SECE task to activation in a cognitive reappraisal task in which participants were asked to attend to, or regulate their emotional reactions to affective IAPS images. This task replicated prefrontal activation seen in previous reappraisal studies. A voxelwise conjunction analysis found no overlap between the cognitive reappraisal and the SECE task, but we did find evidence for common activation in follow-up ROI analyses, supporting the idea of common lateral prefrontal mechanisms involved in both processes.

Social domain based modulation of neural responses to threat: The different roles of romantic partners versus friends.

The neural circuitry associated with threat regulation in the absence of other people is well established. An examination of threat regulatory processes with people from different domains of an individual's social world is key to understanding social emotion regulation and personality functioning conceptualised as social domain organisation. In this study, 42 healthy female participants completed functional magnetic imaging sessions in which they underwent a scan in the presence of a romantic partner or friend, whilst completing a threat of shock task. In the presence of a romantic partner vs. friend, we found a reduction in amygdala activation to threat vs. safe trials over time. Furthermore, in the presence of a romantic partner vs. friend we observed greater subgenual anterior cingulate cortex and ventromedial prefrontal cortex activation to threat vs. safe trials overall. The results support the hypothesis that recruitment of threat regulation circuitry is modulated by romantic partner relative to another person well-known to the individual. Future work needs to examine neural responses to a wider range of stimuli across more social domains, and implications of failures of this neural organisation for psychopathology.

Linguistic markers of moderate and absolute natural language.

In social, personality and mental health research, the tendency to select absolute end-points on Likert scales has been linked to certain cultures, lower intelligence, lower income and personality/mental health disorders. It is unclear whether this response style reflects an absolutist cognitive style or is merely an experimental artefact. In this study, we introduce an alternative, more informative, flexible and ecologically valid approach for estimating absolute responding, that uses natural language markers. We focussed on 'function words' (e.g. particles, conjunctions, prepositions) as they are more generalizable because they do not depend on any specific context. To identify such linguistic markers and test their generalizability, we conducted a text analysis of online reviews for films, tourist attractions and consumer products. All written reviews were accompanied by a rating scale (akin to Likert scale), which allowed us to label text samples as absolute/moderate. The data was split into independent 'training' and 'test' sets. Using the training set we identified a rank order of linguistic markers for absolute and moderate text, which were evaluated in a classifier on the test set. The top three markers alone ("but", "!" and "seem") produced 88% classification accuracy, which increased to 91% using 31 linguistic markers.

In an Absolute State: Elevated Use of Absolutist Words Is a Marker Specific to Anxiety, Depression, and Suicidal Ideation.

Absolutist thinking is considered a cognitive distortion by most cognitive therapies for anxiety and depression. Yet, there is little empirical evidence of its prevalence or specificity. Across three studies, we conducted a text analysis of 63 Internet forums (over 6,400 members) using the Linguistic Inquiry and Word Count software to examine absolutism at the linguistic level. We predicted and found that anxiety, depression, and suicidal ideation forums contained more absolutist words than control forums (ds > 3.14). Suicidal ideation forums also contained more absolutist words than anxiety and depression forums (ds > 1.71). We show that these differences are more reflective of absolutist thinking than psychological distress. It is interesting that absolutist words tracked the severity of affective disorder forums more faithfully than negative emotion words. Finally, we found elevated levels of absolutist words in depression recovery forums. This suggests that absolutist thinking may be a vulnerability factor.

Simultaneous EEG-fMRI reveals attention-dependent coupling of early face processing with a distributed cortical network.

The speed of visual processing is central to our understanding of face perception. Yet the extent to which early visual processing influences later processing in distributed face processing networks, and the top-down modulation of such bottom-up effects, remains unclear. We used simultaneous EEG-fMRI to investigate cortical activity that showed unique covariation with ERP components of face processing (C1, P1, N170, P3), while manipulating sustained attention and transient cognitive conflict employing an emotional face-word Stroop task. ERP markers of visual processing within 100 ms after stimulus onset showed covariation with brain activation in precuneous, posterior cingulate gyrus, left middle temporal gyrus, left inferior frontal gyrus and frontal operculum, and a left lateral parietal-occipital cluster, illustrating the impact of early stage processing on higher-order mechanisms. Crucially, this covariation depended on sustained attentional focus and was absent for incongruent trials, suggesting flexible top-down gating of bottom-up processing.

Sex-Specific Effects of Gender Identification on Pain Study Recruitment.

Epidemiological, clinical, and laboratory studies show sex differences in pain responses, with women more sensitive to nociceptive stimulation and more vulnerable to long-term pain conditions than men. Because of evidence that men are culturally reinforced for the ability to endure (or under-report) pain, some of these findings might be explained by sociocultural beliefs about gender-appropriate behavior. One potential manifestation of these effects might be differential participation in pain studies, with men adhering to stereotypical masculine roles viewing participation as a way to demonstrate their masculinity. To test this possibility, we assessed gender identification in 137 healthy participants. At the end of the assessment, they were asked if they would like to participate in other research studies. Interested participants were then asked to participate in a study involving administration of pain-evoking stimulation. We compared individuals who agreed to participate in the pain study with those who declined. We observed a significant Sex × Participation interaction in masculine gender identification, such that men (but not women) who agreed to participate identified significantly more with masculine gender. Among masculine gender traits examined, we found that high levels of aggression and competitiveness were the strongest predictors of pain study participation. Our results suggest that men in pain studies might have higher levels of masculine gender identification than the wider male population. Taken together with previous findings of lower levels of pain sensitivity (or reporting) in masculine-identifying male participants, these results suggest an explanation for some of the sex-related differences observed in pain responses. PERSPECTIVE: To examine whether sex and gender affect willingness to participate in pain studies, we assessed gender identification in men and women, then attempted to recruit them to participate in a pain study. Men who agree to participate in pain studies are significantly higher in masculine gender identification than men who decline to participate or women who agree to participate. Men who agreed to participate were rated particularly high in aggressiveness and competitiveness.

Amygdala volume and hypothalamic-pituitary-adrenal axis reactivity to social stress.

The amygdala plays a central role in emotional processing and has an activating influence on the hypothalamic-pituitary-adrenal (HPA) axis. Structural changes in the amygdala have been associated with early adversity and, in principle, may contribute to the later emergence of emotional pathologies by influencing the way that the brain responds to stress provocation. The present study examined the relationship between amygdala volumes and cortisol secretion in response to a social stressor among young adults who were or were not exposed to maternal postnatal depression (PND) early in development (referred to as PND offspring and controls, respectively). Hierarchical Linear Modelling (HLM) revealed that, on a sample-wide level, there was no evidence of a relationship between total amygdala volume, or the volume of the right or left hemisphere amygdala taken separately, and cortisol reactivity. Unexpectedly, for PND offspring, larger right hemisphere amygdala volume was associated with lower cortisol reactivity in response to stress, an effect that was not apparent in control offspring. We conclude that the relationship between amygdala volumes and stress reactivity may not be as clear as previous models suggested.

Sliding-window analysis tracks fluctuations in amygdala functional connectivity associated with physiological arousal and vigilance during fear conditioning.

We evaluated whether sliding-window analysis can reveal functionally relevant brain network dynamics during a well-established fear conditioning paradigm. To this end, we tested if fMRI fluctuations in amygdala functional connectivity (FC) can be related to task-induced changes in physiological arousal and vigilance, as reflected in the skin conductance level (SCL). Thirty-two healthy individuals participated in the study. For the sliding-window analysis we used windows that were shifted by one volume at a time. Amygdala FC was calculated for each of these windows. Simultaneously acquired SCL time series were averaged over time frames that corresponded to the sliding-window FC analysis, which were subsequently regressed against the whole-brain seed-based amygdala sliding-window FC using the GLM. Surrogate time series were generated to test whether connectivity dynamics could have occurred by chance. In addition, results were contrasted against static amygdala FC and sliding-window FC of the primary visual cortex, which was chosen as a control seed, while a physio-physiological interaction (PPI) was performed as cross-validation. During periods of increased SCL, the left amygdala became more strongly coupled with the bilateral insula and anterior cingulate cortex, core areas of the salience network. The sliding-window analysis yielded a connectivity pattern that was unlikely to have occurred by chance, was spatially distinct from static amygdala FC and from sliding-window FC of the primary visual cortex, but was highly comparable to that of the PPI analysis. We conclude that sliding-window analysis can reveal functionally relevant fluctuations in connectivity in the context of an externally cued task.

Sweet taste pleasantness is modulated by morphine and naltrexone.

BACKGROUND: Rodent models highlight the key role of µ-opioid receptor (MOR) signaling in palatable food consumption. In humans, however, the effects of MOR stimulation on eating and food liking remain unclear. OBJECTIVES: Here, we tested sweet pleasantness experience in humans following MOR drug manipulations. We hypothesized that behaviors regulated by the endogenous MOR system would be enhanced by MOR agonism and decreased by antagonism. In line with rodent findings, we expected the strongest drug effects for the sweetest (high-calorie) sucrose stimuli. As very sweet stimuli are considered aversive by many people (called sweet dislikers), we also assessed whether MOR manipulations affect pleasantness ratings of sucrose-water stimuli differently depending on subjective and objective value. METHODS: In a bidirectional psychopharmacological cross-over study, 49 healthy men underwent a sweet taste paradigm following double-blind administration of the MOR agonist morphine, placebo, and the opioid antagonist naltrexone. RESULTS: As hypothesized, MOR stimulation with morphine increased pleasantness of the sweetest of five sucrose solutions, without enhancing pleasantness of the lower-sucrose solutions. For opioid antagonism, an opposite pattern was observed for the sweetest drink only. The observed drug effects on pleasantness of the sweetest drink did not differ between sweet likers and dislikers. CONCLUSIONS: The bidirectional effect of agonist and antagonist treatment aligns with rodent findings showing that MOR manipulations most strongly affect the highest-calorie foods. We speculate that the MOR system promotes survival in part by increasing concordance between the objective (caloric) and subjective (hedonic) value of food stimuli, so that feeding behavior becomes more focused on the richest food available.

Altered engagement of autobiographical memory networks in adult offspring of postnatally depressed mothers.

Maternal depression is associated with increased risk for offspring mood and anxiety disorders. One possible impact of maternal depression during offspring development is on the emotional autobiographical memory system. We investigated the neural mechanisms of emotional autobiographical memory in adult offspring of mothers with postnatal depression (N=16) compared to controls (N=21). During fMRI, recordings of participants describing one pleasant and one unpleasant situation with their mother and with a companion, were used as prompts to re-live the situations. Compared to controls we predicted the PND offspring would show: greater activation in medial and posterior brain regions implicated in autobiographical memory and rumination; and decreased activation in lateral prefrontal cortex and decreased connectivity between lateral prefrontal and posterior regions, reflecting reduced control of autobiographical recall. For negative situations, we found no group differences. For positive situations with their mothers, PND offspring showed higher activation than controls in left lateral prefrontal cortex, right frontal pole, cingulate cortex and precuneus, and lower connectivity of right middle frontal gyrus, left middle temporal gyrus, thalamus and lingual gyrus with the posterior cingulate. Our results are consistent with adult offspring of PND mothers having less efficient prefrontal regulation of personally relevant pleasant autobiographical memories.

Neural emotion regulation circuitry underlying anxiolytic effects of perceived control over pain.

Anxiolytic effects of perceived control have been observed across species. In humans, neuroimaging studies have suggested that perceived control and cognitive reappraisal reduce negative affect through similar mechanisms. An important limitation of extant neuroimaging studies of perceived control in terms of directly testing this hypothesis, however, is the use of within-subject designs, which confound participants' affective response to controllable and uncontrollable stress. To compare neural and affective responses when participants were exposed to either uncontrollable or controllable stress, two groups of participants received an identical series of stressors (thermal pain stimuli). One group ("controllable") was led to believe they had behavioral control over the pain stimuli, whereas another ("uncontrollable") believed they had no control. Controllable pain was associated with decreased state anxiety, decreased activation in amygdala, and increased activation in nucleus accumbens. In participants who perceived control over the pain, reduced state anxiety was associated with increased functional connectivity between each of these regions and ventral lateral/ventral medial pFC. The location of pFC findings is consistent with regions found to be critical for the anxiolytic effects of perceived control in rodents. Furthermore, interactions observed between pFC and both amygdala and nucleus accumbens are remarkably similar to neural mechanisms of emotion regulation through reappraisal in humans. These results suggest that perceived control reduces negative affect through a general mechanism involved in the cognitive regulation of emotion.

Insecure attachment during infancy predicts greater amygdala volumes in early adulthood.

BACKGROUND: The quality of the early environment is hypothesized to be an influence on morphological development in key neural areas related to affective responding, but direct evidence to support this possibility is limited. In a 22-year longitudinal study, we examined hippocampal and amygdala volumes in adulthood in relation to early infant attachment status, an important indicator of the quality of the early caregiving environment. METHODS: Participants (N = 59) were derived from a prospective longitudinal study of the impact of maternal postnatal depression on child development. Infant attachment status (35 Secure; 24 Insecure) was observed at 18 months of age, and MRI assessments were completed at 22 years [corrected]. RESULTS: In line with hypotheses, insecure versus secure infant attachment status was associated with larger amygdala volumes in young adults, an effect that was not accounted for by maternal depression history. We did not find early infant attachment status to predict hippocampal volumes. CONCLUSIONS: Common variations in the quality of early environment are associated with gross alterations in amygdala morphology in the adult brain. Further research is required to establish the neural changes that underpin the volumetric differences reported here, and any functional implications.

FMRI evidence for the involvement of the procedural memory system in morphological processing of a second language.

Behavioural evidence suggests that English regular past tense forms are automatically decomposed into their stem and affix (played  = play+ed) based on an implicit linguistic rule, which does not apply to the idiosyncratically formed irregular forms (kept). Additionally, regular, but not irregular inflections, are thought to be processed through the procedural memory system (left inferior frontal gyrus, basal ganglia, cerebellum). It has been suggested that this distinction does not to apply to second language (L2) learners of English; however, this has not been tested at the brain level. This fMRI study used a masked-priming task with regular and irregular prime-target pairs (played-play/kept-keep) to investigate morphological processing in native and highly proficient late L2 English speakers. No between-groups differences were revealed. Compared to irregular pairs, regular pairs activated the pars opercularis, bilateral caudate nucleus and the right cerebellum, which are part of the procedural memory network and have been connected with the processing of morphologically complex forms. Our study is the first to provide evidence for native-like involvement of the procedural memory system in processing of regular past tense by late L2 learners of English.