Continuous evaluation of denoising strategies in resting-state fMRI connectivity using fMRIPrep and Nilearn.

Reducing contributions from non-neuronal sources is a crucial step in functional magnetic resonance imaging (fMRI) connectivity analyses. Many viable strategies for denoising fMRI are used in the literature, and practitioners rely on denoising benchmarks for guidance in the selection of an appropriate choice for their study. However, fMRI denoising software is an ever-evolving field, and the benchmarks can quickly become obsolete as the techniques or implementations change. In this work, we present a denoising benchmark featuring a range of denoising strategies, datasets and evaluation metrics for connectivity analyses, based on the popular fMRIprep software. The benchmark prototypes an implementation of a reproducible framework, where the provided Jupyter Book enables readers to reproduce or modify the figures on the Neurolibre reproducible preprint server (https://neurolibre.org/). We demonstrate how such a reproducible benchmark can be used for continuous evaluation of research software, by comparing two versions of the fMRIprep. Most of the benchmark results were consistent with prior literature. Scrubbing, a technique which excludes time points with excessive motion, combined with global signal regression, is generally effective at noise removal. Scrubbing was generally effective, but is incompatible with statistical analyses requiring the continuous sampling of brain signal, for which a simpler strategy, using motion parameters, average activity in select brain compartments, and global signal regression, is preferred. Importantly, we found that certain denoising strategies behave inconsistently across datasets and/or versions of fMRIPrep, or had a different behavior than in previously published benchmarks. This work will hopefully provide useful guidelines for the fMRIprep users community, and highlight the importance of continuous evaluation of research methods.

Experience sampling reveals the role that covert goal states play in task-relevant behavior.

Cognitive neuroscience has gained insight into covert states using experience sampling. Traditionally, this approach has focused on off-task states. However, task-relevant states are also maintained via covert processes. Our study examined whether experience sampling can also provide insights into covert goal-relevant states that support task performance. To address this question, we developed a neural state space, using dimensions of brain function variation, that allows neural correlates of overt and covert states to be examined in a common analytic space. We use this to describe brain activity during task performance, its relation to covert states identified via experience sampling, and links between individual variation in overt and covert states and task performance. Our study established deliberate task focus was linked to faster target detection, and brain states underlying this experience-and target detection-were associated with activity patterns emphasizing the fronto-parietal network. In contrast, brain states underlying off-task experiences-and vigilance periods-were linked to activity patterns emphasizing the default mode network. Our study shows experience sampling can not only describe covert states that are unrelated to the task at hand, but can also be used to highlight the role fronto-parietal regions play in the maintenance of covert task-relevant states.

Continuous Evaluation of Denoising Strategies in Resting-State fMRI Connectivity Using fMRIPrep and Nilearn.

Reducing contributions from non-neuronal sources is a crucial step in functional magnetic resonance imaging (fMRI) connectivity analyses. Many viable strategies for denoising fMRI are used in the literature, and practitioners rely on denoising benchmarks for guidance in the selection of an appropriate choice for their study. However, fMRI denoising software is an ever-evolving field, and the benchmarks can quickly become obsolete as the techniques or implementations change. In this work, we present a denoising benchmark featuring a range of denoising strategies, datasets and evaluation metrics for connectivity analyses, based on the popular fMRIprep software. The benchmark is implemented in a fully reproducible framework, where the provided research objects enable readers to reproduce or modify core computations, as well as the figures of the article using the Jupyter Book project and the Neurolibre reproducible preprint server (https://neurolibre.org/). We demonstrate how such a reproducible benchmark can be used for continuous evaluation of research software, by comparing two versions of the fMRIprep software package. The majority of benchmark results were consistent with prior literature. Scrubbing, a technique which excludes time points with excessive motion, combined with global signal regression, is generally effective at noise removal. Scrubbing however disrupts the continuous sampling of brain images and is incompatible with some statistical analyses, e.g. auto-regressive modeling. In this case, a simple strategy using motion parameters, average activity in select brain compartments, and global signal regression should be preferred. Importantly, we found that certain denoising strategies behave inconsistently across datasets and/or versions of fMRIPrep, or had a different behavior than in previously published benchmarks. This work will hopefully provide useful guidelines for the fMRIprep users community, and highlight the importance of continuous evaluation of research methods. Our reproducible benchmark infrastructure will facilitate such continuous evaluation in the future, and may also be applied broadly to different tools or even research fields.

Higher Sensory Sensitivity is Linked to Greater Expansion Amongst Functional Connectivity Gradients.

Insofar as the autistic-like phenotype presents in the general population, it consists of partially dissociable traits, such as social and sensory issues. Here, we investigate individual differences in cortical organisation related to autistic-like traits. Connectome gradient decomposition based on resting state fMRI data reliably reveals a principal gradient spanning from unimodal to transmodal regions, reflecting the transition from perception to abstract cognition. In our non-clinical sample, this gradient's expansion, indicating less integration between visual and default mode networks, correlates with subjective sensory sensitivity (measured using the Glasgow Sensory Questionnaire, GSQ), but not other autistic-like traits (measured using the Autism Spectrum Quotient, AQ). This novel brain-based correlate of the GSQ demonstrates sensory issues can be disentangled from the wider autistic-like phenotype.

Comparing the bond strength of fiber post cementation in the root canal using pre- and co-curing procedures with the same self-etching bonding system.

Background/purpose: Self-etching bonding systems are widely used in fiber post cementation. However, no clear guidelines are established for choosing pre- or co-curing procedures. We investigated the bond strength of fiber post cementation using pre-/co-curing methods in self-etching bonding systems and compared them with those of a self-adhesive system. Materials and methods: Post spaces were prepared in 30 single-rooted premolars/canines, and the fiber posts were cemented in three ways (10 specimens per group): using a self-etching bonding system with either a pre-curing or simultaneous co-curing procedure (RelyX™ Ultimate; groups SE-pre and SE-co, respectively) and using a self-adhesive system (RelyX™ Unicem 2, group SA). Each specimen was embedded and sliced perpendicularly to the long axis into three 2.5-mm-thick sections. Microphotographs of the coronal and apical surfaces of each section were acquired, and push-out tests (1 mm/min) were performed. One-way analysis of variance was conducted on the data, followed by Tukey's honestly significant difference post hoc test. Results: The bond strength in the whole root was not significantly different among the three groups. When independently evaluating each portion, group SE-co exhibited significantly lower coronal bond strength. The bond strength varied among root regions only in group SE-pre; the apical region had a significantly lower value. Conclusion: No cementation method is superior in all portions. Regarding pre-curing methods, clinicians must caution the fit between the post and post space, which may be affected by the pre-polymerized bond layer. The co-curing method used in a larger coronal cement space contributes to the poor bond strength.

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.

Voice Hearing in Borderline Personality Disorder Across Perceptual, Subjective, and Neural Dimensions.

BACKGROUND: Auditory verbal hallucinations (AVH) commonly occur in the context of borderline personality disorder (BPD) yet remain poorly understood. AVH are often perceived by patients with BPD as originating from inside the head and hence viewed clinically as "pseudohallucinations," but they nevertheless have a detrimental impact on well-being. METHODS: The current study characterized perceptual, subjective, and neural expressions of AVH by using an auditory detection task, experience sampling and questionnaires, and functional neuroimaging, respectively. RESULTS: Perceptually, reported AVH correlated with a bias for reporting the presence of a voice in white noise. Subjectively, questionnaire measures indicated that AVH were significantly distressing and persecutory. In addition, AVH intensity, but not perceived origin (i.e., inside vs outside the head), was associated with greater concurrent anxiety. Neurally, fMRI of BPD participants demonstrated that, relative to imagining or listening to voices, periods of reported AVH induced greater blood oxygenation level-dependent activity in anterior cingulate and bilateral temporal cortices (regional substrates for language processing). AVH symptom severity was associated with weaker functional connectivity between anterior cingulate and bilateral insular cortices. CONCLUSION: In summary, our results indicate that AVH in participants with BPD are (1) underpinned by aberrant perceptual-cognitive mechanisms for signal detection, (2) experienced subjectively as persecutory and distressing, and (3) associated with distinct patterns of neural activity that inform proximal mechanistic understanding. Our findings are like analogous observations in patients with schizophrenia and validate the clinical significance of the AVH experience in BPD, often dismissed as "pseudohallucinations." These highlight a need to reconsider this experience as a treatment priority.

Brainhack: Developing a culture of open, inclusive, community-driven neuroscience.

Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress.

The neural correlates of ongoing conscious thought.

A core goal in cognitive neuroscience is identifying the physical substrates of the patterns of thought that occupy our daily lives. Contemporary views suggest that the landscape of ongoing experience is heterogeneous and can be influenced by features of both the person and the context. This perspective piece considers recent work that explicitly accounts for both the heterogeneity of the experience and context dependence of patterns of ongoing thought. These studies reveal that systems linked to attention and control are important for organizing experience in response to changing environmental demands. These studies also establish a role of the default mode network beyond task-negative or purely episodic content, for example, implicating it in the level of vivid detail in experience in both task contexts and in spontaneous self-generated experiential states. Together, this work demonstrates that the landscape of ongoing thought is reflected in the activity of multiple neural systems, and it is important to distinguish between processes contributing to how the experience unfolds from those linked to how these experiences are regulated.

Missing the forest because of the trees: slower alternations during binocular rivalry are associated with lower levels of visual detail during ongoing thought.

Conscious awareness of the world fluctuates, either through variation in how vividly we perceive the environment, or when our attentional focus shifts away from information in the external environment towards information that we generate via imagination. Our study combined individual differences in experience sampling, psychophysical reports of perception and neuroimaging descriptions of structural connectivity to better understand these changes in conscious awareness. In particular, we examined (i) whether aspects of ongoing thought-indexed via multi-dimensional experience sampling during a sustained attention task-are associated with the white matter fibre organization of the cortex as reflected by their relative degree of anisotropic diffusion and (ii) whether these neurocognitive descriptions of ongoing experience are related to a more constrained measure of visual consciousness through analysis of bistable perception during binocular rivalry. Individuals with greater fractional anisotropy in right hemisphere white matter regions involving the inferior fronto-occipital fasciculus, the superior longitudinal fasciculus and the cortico-spinal tract, described their ongoing thoughts as lacking external details. Subsequent analysis indicated that the combination of low fractional anisotropy in these right hemisphere regions, with reports of thoughts with high levels of external details, was associated with the shortest periods of dominance during binocular rivalry. Since variation in binocular rivalry reflects differences between bottom-up and top-down influences on vision, our study suggests that reports of ongoing thoughts with vivid external details may occur when conscious precedence is given to bottom-up representation of perceptual information.

Author Correction: Reductions in task positive neural systems occur with the passage of time and are associated with changes in ongoing thought.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Neurocognitive patterns dissociating semantic processing from executive control are linked to more detailed off-task mental time travel.

Features of ongoing experience are common across individuals and cultures. However, certain people express specific patterns of thought to a greater extent than others. Contemporary psychological theory assumes that individual differences in thought patterns occur because different types of experience depend on the expression of different neurocognitive processes. Consequently, individual variation in the underlying neurocognitive architecture is hypothesised to determine the ease with which certain thought patterns are generated or maintained. Our study (N = 178) tested this hypothesis using multivariate pattern analysis to infer shared variance among measures of cognitive function and neural organisation and examined whether these latent variables explained reports of the patterns of on-going thoughts people experienced in the lab. We found that relatively better performance on tasks relying primarily on semantic knowledge, rather than executive control, was linked to a neural functional organisation associated, via meta-analysis, with task labels related to semantic associations (sentence processing, reading and verbal semantics). Variability of this functional mode predicted significant individual variation in the types of thoughts that individuals experienced in the laboratory: neurocognitive patterns linked to better performance at tasks that required guidance from semantic representation, rather than those dependent on executive control, were associated with patterns of thought characterised by greater subjective detail and a focus on time periods other than the here and now. These relationships were consistent across different days and did not vary with level of task demands, indicating they are relatively stable features of an individual's cognitive profile. Together these data confirm that individual variation in aspects of ongoing experience can be inferred from hidden neurocognitive architecture and demonstrate that performance trade-offs between executive control and long-term semantic knowledge are linked to a person's tendency to imagine situations that transcend the here and now.

The relationship between individual variation in macroscale functional gradients and distinct aspects of ongoing thought.

Contemporary accounts of ongoing thought recognise it as a heterogeneous and multidimensional construct, varying in both form and content. An emerging body of evidence demonstrates that distinct types of experience are associated with unique neurocognitive profiles, that can be described at the whole-brain level as interactions between multiple large-scale networks. The current study sought to explore the possibility that whole-brain functional connectivity patterns at rest may be meaningfully related to patterns of ongoing thought that occurred over this period. Participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) followed by a questionnaire retrospectively assessing the content and form of their ongoing thoughts during the scan. A non-linear dimension reduction algorithm was applied to the rs-fMRI data to identify components explaining the greatest variance in whole-brain connectivity patterns. Using these data, we examined whether specific types of thought measured at the end of the scan were predictive of individual variation along the first three low-dimensional components of functional connectivity at rest. Multivariate analyses revealed that individuals for whom the connectivity of the sensorimotor system was maximally distinct from the visual system were most likely to report thoughts related to finding solutions to problems or goals and least likely to report thoughts related to the past. These results add to an emerging literature that suggests that unique patterns of experience are associated with distinct distributed neurocognitive profiles and highlight that unimodal systems may play an important role in this process.

Reductions in task positive neural systems occur with the passage of time and are associated with changes in ongoing thought.

Cognition is dynamic and involves both the maintenance of and transitions between neurocognitive states. While recent research has identified some of the neural systems involved in sustaining task states, it is less well understood how intrinsic influences on cognition emerge over time. The current study uses fMRI and Multi-Dimensional Experience Sampling (MDES) to chart how cognition changes over time from moments in time when external attention was established. We found that the passage of time was associated with brain regions associated with external attention decreasing in activity over time. Comparing this pattern of activity to defined functional hierarchies of brain organization, we found that it could be best understood as movement away from systems involved in task performance. Moments where the participants described their thoughts as off-task showed a significant similarity to the task-negative end of the same hierarchy. Finally, the greater the similarity of a participant's neural dynamics to this hierarchy the faster their rate of increasing off-task thought over time. These findings suggest topographical changes in neural processing that emerge over time and those seen during off-task thought can both be understood as a common shift away from neural motifs seen during complex task performance.

A role for the ventromedial prefrontal cortex in self-generated episodic social cognition.

The human mind is equally fluent in thoughts that involve self-generated mental content as it is with information in the immediate environment. Previous research has shown that neural systems linked to executive control (i.e. the dorsolateral prefrontal cortex) are recruited when perceptual and self-generated thoughts are balanced in line with the demands imposed by the external world. Contemporary theories (Smallwood and Schooler, 2015) assume that differentiable processes are important for self-generated mental content than for its regulation. The current study used functional magnetic resonance imaging in combination with multidimensional experience sampling to address this possibility. We used a task with minimal demands to maximise our power at identifying correlates of self-generated states. Principal component analysis showed consistent patterns of self-generated thought when participants performed the task in either the lab or in the scanner (ICC ranged from 0.68 to 0.86). In a whole brain analyses we found that neural activity in the ventromedial prefrontal cortex (vMPFC) increases when participants are engaged in experiences which emphasise episodic and socio-cognitive features. Our study suggests that neural activity in the vMPFC is linked to patterns of ongoing thought, particularly those with episodic or social features.

Finding the needle in a high-dimensional haystack: Canonical correlation analysis for neuroscientists.

The 21st century marks the emergence of "big data" with a rapid increase in the availability of datasets with multiple measurements. In neuroscience, brain-imaging datasets are more commonly accompanied by dozens or hundreds of phenotypic subject descriptors on the behavioral, neural, and genomic level. The complexity of such "big data" repositories offer new opportunities and pose new challenges for systems neuroscience. Canonical correlation analysis (CCA) is a prototypical family of methods that is useful in identifying the links between variable sets from different modalities. Importantly, CCA is well suited to describing relationships across multiple sets of data, such as in recently available big biomedical datasets. Our primer discusses the rationale, promises, and pitfalls of CCA.

Hello, is that me you are looking for? A re-examination of the role of the DMN in social and self relevant aspects of off-task thought.

Neural activity within the default mode network (DMN) is widely assumed to relate to processing during off-task states, however it remains unclear whether this association emerges from a shared role in self or social content that is common in these conditions. In the current study, we examine the possibility that the role of the DMN in ongoing thought emerges from contributions to specific features of off-task experience such as self-relevant or social content. A group of participants described their experiences while performing a laboratory task over a period of days. In a different session, neural activity was measured while participants performed Self/Other judgements (e.g., Does the word 'Honest' apply to you (Self condition) or Barack Obama (Other condition)). Despite the prominence of social and personal content in off-task reports, there was no association with neural activity during off-task trait adjective judgements. Instead, during both Self and Other judgements we found recruitment of caudal posterior cingulate cortex-a core DMN hub-was above baseline for individuals whose laboratory experiences were characterised as detailed. These data provide little support for a role of the DMN in self or other content in the off-task state and instead suggest a role in how on-going thought is represented.

Reduced semantic control in older adults is linked to intrinsic DMN connectivity.

Ageing provides an interesting window into semantic cognition: while younger adults generally outperform older adults on many cognitive tasks, knowledge continues to accumulate over the lifespan and consequently, the semantic store (i.e., vocabulary size) remains stable (or even improves) during healthy ageing. Semantic cognition involves the interaction of at least two components - a semantic store and control processes that interact to ensure efficient and context-relevant use of representations. Given older adults perform less well on tasks measuring executive control, their ability to access the semantic store in a goal driven manner may be compromised. Older adults also consistently show reductions in intrinsic brain connectivity, and we examined how these brain changes relate to age-related changes in semantic performance. We found that while older participants outperformed their younger counterparts on tests of vocabulary size (i.e., NART), younger participants were faster and more accurate in tasks requiring semantic control, and these age differences correlated with measures of intrinsic connectivity between the anterior temporal lobe (ATL) and medial prefrontal cortex (mPFC), within the default mode network. Higher intrinsic connectivity from right ATL to mPFC at rest related to better performance on verbal (but not picture) semantic tasks, and older adults showed an exaggerated version of this pattern, suggesting that this within-DMN connectivity may become more important for conceptual access from words as we age. However, this appeared to be at the expense of control over semantic retrieval - there was little relationship between connectivity and performance for strong associations in either group, but older adults with stronger connectivity showed particularly inefficient retrieval of weak associations. Older adults may struggle to harness the default mode network to support demanding patterns of semantic retrieval, resulting in a performance cost.

Patterns of on-task thought in older age are associated with changes in functional connectivity between temporal and prefrontal regions.

Humans spend a large proportion of their time engaged in thoughts unrelated to the task being performed, a tendency that declines with age. However, a clear neuro-cognitive account of what underlies this decrease is lacking. This study addresses the possibility that age-related changes in off-task thinking are correlated with changes in the intrinsic organisation of the brain. Laboratory measures of ongoing thought were recorded in young and older individuals, who also participated in a resting state fMRI experiment. Older individuals showed reduced connectivity between the left anterior temporal lobe with prefrontal aspects of the DMN. We found that off-task thinking did not increase when task demands were lower for older adults, which is a pattern repeatedly seen in younger individuals. Finally, we demonstrated that these neural and thought patterns were linked - for younger participants only, reductions in the strength of connectivity were related to a greater shift towards off-task thoughts when task demands decreased. Importantly, in the older individuals, lower connectivity between the same regions was linked to preserved performance on a creativity task. These data suggest that the age-related reduction of off-task thought may be related to reduced communication between temporal and prefrontal DMN regions in ageing.