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.

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.

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.

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.

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.

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.

Grey matter volume in the cerebellum is related to the processing of grammatical rules in a second language: a structural voxel-based morphometry study.

The experience of learning and using a second language (L2) has been shown to affect the grey matter (GM) structure of the brain. Importantly, GM density in several cortical and subcortical areas has been shown to be related to performance in L2 tasks. Here, we show that bilingualism can lead to increased GM volume in the cerebellum, a structure that has been related to the processing of grammatical rules. Additionally, the cerebellar GM volume of highly proficient L2 speakers is correlated to their performance in a task tapping on grammatical processing in an L2, demonstrating the importance of the cerebellum for the establishment and use of grammatical rules in an L2.

Making an effort to feel positive: insecure attachment in infancy predicts the neural underpinnings of emotion regulation in adulthood.

BACKGROUND: Animal research indicates that the neural substrates of emotion regulation may be persistently altered by early environmental exposures. If similar processes operate in human development then this is significant, as the capacity to regulate emotional states is fundamental to human adaptation. METHODS: We utilised a 22-year longitudinal study to examine the influence of early infant attachment to the mother, a key marker of early experience, on neural regulation of emotional states in young adults. Infant attachment status was measured via objective assessment at 18-months, and the neural underpinnings of the active regulation of affect were studied using fMRI at age 22 years. RESULTS: Infant attachment status at 18-months predicted neural responding during the regulation of positive affect 20-years later. Specifically, while attempting to up-regulate positive emotions, adults who had been insecurely versus securely attached as infants showed greater activation in prefrontal regions involved in cognitive control and reduced co-activation of nucleus accumbens with prefrontal cortex, consistent with relative inefficiency in the neural regulation of positive affect. CONCLUSIONS: Disturbances in the mother-infant relationship may persistently alter the neural circuitry of emotion regulation, with potential implications for adjustment in adulthood.

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.

Turning on the alarm: the neural mechanisms of the transition from innocuous to painful sensation.

The experience of pain occurs when the level of a stimulus is sufficient to elicit a marked affective response, putatively to warn the organism of potential danger and motivate appropriate behavioral responses. Understanding the biological mechanisms of the transition from innocuous to painful levels of sensation is essential to understanding pain perception as well as clinical conditions characterized by abnormal relationships between stimulation and pain response. Thus, the primary objective of this study was to characterize the neural response associated with this transition and the correspondence between that response and subjective reports of pain. Towards this goal, this study examined BOLD response profiles across a range of temperatures spanning the pain threshold. 14 healthy adults underwent functional magnetic resonance imaging (fMRI) while a range of thermal stimuli (44-49°C) were applied. BOLD responses showed a sigmoidal profile along the range of temperatures in a network of brain regions including insula and mid-cingulate, as well as a number of regions associated with motor responses including ventral lateral nuclei of the thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD responses in these regions explained up to 85% of the variance in individual pain ratings, and yielded an estimate of the temperature of steepest transition from non-painful to painful heat that was nearly identical to that generated by subjective ratings. These results demonstrate a precise characterization of the relationship between objective levels of stimulation, resulting neural activation, and subjective experience of pain and provide direct evidence for a neural mechanism supporting the nonlinear transition from innocuous to painful levels along the sensory continuum.

Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation.

Anhedonia, the loss of pleasure or interest in previously rewarding stimuli, is a core feature of major depression. While theorists have argued that anhedonia reflects a reduced capacity to experience pleasure, evidence is mixed as to whether anhedonia is caused by a reduction in hedonic capacity. An alternative explanation is that anhedonia is due to the inability to sustain positive affect across time. Using positive images, we used an emotion regulation task to test whether individuals with depression are unable to sustain activation in neural circuits underlying positive affect and reward. While up-regulating positive affect, depressed individuals failed to sustain nucleus accumbens activity over time compared with controls. This decreased capacity was related to individual differences in self-reported positive affect. Connectivity analyses further implicated the fronto-striatal network in anhedonia. These findings support the hypothesis that anhedonia in depressed patients reflects the inability to sustain engagement of structures involved in positive affect and reward.

Regional response differences across the human amygdaloid complex during social conditioning.

The amygdala is consistently implicated in biologically relevant learning tasks such as Pavlovian conditioning. In humans, the ability to identify individual faces based on the social outcomes they have predicted in the past constitutes a critical form of associative learning that can be likened to "social conditioning." To capture such learning in a laboratory setting, participants learned about faces that predicted negative, positive, or neutral social outcomes. Participants reported liking or disliking the faces in accordance with their learned social value. During acquisition, we observed differential functional magnetic resonance imaging activation across the human amygdaloid complex consistent with previous lesion, electrophysiological, and functional neuroimaging data. A region of the medial ventral amygdala and a region of the dorsal amygdala/substantia innominata showed signal increases to both Negative and Positive faces, whereas a lateral ventral region displayed a linear representation of the valence of faces such that Negative > Positive > Neutral. This lateral ventral locus also differed from the dorsal and medial loci in that the magnitude of these responses was more resistant to habituation. These findings document a role for the human amygdala in social learning and reveal coarse regional dissociations in amygdala activity that are consistent with previous human and nonhuman animal data.

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.

Dynamic Causal Modeling applied to fMRI data shows high reliability.

Sensitivity, specificity, and reproducibility are vital to interpret neuroscientific results from functional magnetic resonance imaging (fMRI) experiments. Here we examine the scan-rescan reliability of the percent signal change (PSC) and parameters estimated using Dynamic Causal Modeling (DCM) in scans taken in the same scan session, less than 5 min apart. We find fair to good reliability of PSC in regions that are involved with the task, and fair to excellent reliability with DCM. Also, the DCM analysis uncovers group differences that were not present in the analysis of PSC, which implies that DCM may be more sensitive to the nuances of signal changes in fMRI data.

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.

Individual differences in some (but not all) medial prefrontal regions reflect cognitive demand while regulating unpleasant emotion.

The present study investigated the premise that individual differences in autonomic physiology could be used to specify the nature and consequences of information processing taking place in medial prefrontal regions during cognitive reappraisal of unpleasant pictures. Neural (blood oxygenation level-dependent functional magnetic resonance imaging) and autonomic (electrodermal [EDA], pupil diameter, cardiac acceleration) signals were recorded simultaneously as twenty-six older people (ages 64-66 years) used reappraisal to increase, maintain, or decrease their responses to unpleasant pictures. EDA was higher when increasing and lower when decreasing compared to maintaining. This suggested modulation of emotional arousal by reappraisal. By contrast, pupil diameter and cardiac acceleration were higher when increasing and decreasing compared to maintaining. This suggested modulation of cognitive demand. Importantly, reappraisal-related activation (increase, decrease>maintain) in two medial prefrontal regions (dorsal medial frontal gyrus and dorsal cingulate gyrus) was correlated with greater cardiac acceleration (increase, decrease>maintain) and monotonic changes in EDA (increase>maintain>decrease). These data indicate that these two medial prefrontal regions are involved in the allocation of cognitive resources to regulate unpleasant emotion, and that they modulate emotional arousal in accordance with the regulatory goal. The emotional arousal effects were mediated by the right amygdala. Reappraisal-related activation in a third medial prefrontal region (subgenual anterior cingulate cortex) was not associated with similar patterns of change in any of the autonomic measures, thus highlighting regional specificity in the degree to which cognitive demand is reflected in medial prefrontal activation during reappraisal.

Gaze fixation and the neural circuitry of face processing in autism.

Diminished gaze fixation is one of the core features of autism and has been proposed to be associated with abnormalities in the neural circuitry of affect. We tested this hypothesis in two separate studies using eye tracking while measuring functional brain activity during facial discrimination tasks in individuals with autism and in typically developing individuals. Activation in the fusiform gyrus and amygdala was strongly and positively correlated with the time spent fixating the eyes in the autistic group in both studies, suggesting that diminished gaze fixation may account for the fusiform hypoactivation to faces commonly reported in autism. In addition, variation in eye fixation within autistic individuals was strongly and positively associated with amygdala activation across both studies, suggesting a heightened emotional response associated with gaze fixation in autism.