Variability in the analysis of a single neuroimaging dataset by many teams.

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.

Sensitivity and specificity of the action observation network to kinematics, target object, and gesture meaning.

Hierarchical models have been proposed to explain how the brain encodes actions, whereby different areas represent different features, such as gesture kinematics, target object, action goal, and meaning. The visual processing of action-related information is distributed over a well-known network of brain regions spanning separate anatomical areas, attuned to specific stimulus properties, and referred to as action observation network (AON). To determine the brain organization of these features, we measured representational geometries during the observation of a large set of transitive and intransitive gestures in two independent functional magnetic resonance imaging experiments. We provided evidence for a partial dissociation between kinematics, object characteristics, and action meaning in the occipito-parietal, ventro-temporal, and lateral occipito-temporal cortex, respectively. Importantly, most of the AON showed low specificity to all the explored features, and representational spaces sharing similar information content were spread across the cortex without being anatomically adjacent. Overall, our results support the notion that the AON relies on overlapping and distributed coding and may act as a unique representational space instead of mapping features in a modular and segregated manner.

The structure underlying core affect and perceived affective qualities of human vocal bursts.

Vocal bursts are non-linguistic affectively-laden sounds with a crucial function in human communication, yet their affective structure is still debated. Studies showed that ratings of valence and arousal follow a V-shaped relationship in several kinds of stimuli: high arousal ratings are more likely to go on a par with very negative or very positive valence. Across two studies, we asked participants to listen to 1,008 vocal bursts and judge both how they felt when listening to the sound (i.e. core affect condition), and how the speaker felt when producing it (i.e. perception of affective quality condition). We show that a V-shaped fit outperforms a linear model in explaining the valence-arousal relationship across conditions and studies, even after equating the number of exemplars across emotion categories. Also, although subjective experience can be significantly predicted using affective quality ratings, core affect scores are significantly lower in arousal, less extreme in valence, more variable between individuals, and less reproducible between studies. Nonetheless, stimuli rated with opposite valence between conditions range from 11% (study 1) to 17% (study 2). Lastly, we demonstrate that ambiguity in valence (i.e. high between-participants variability) explains violations of the V-shape and relates to higher arousal.

Emotion Regulation Failures Are Preceded by Local Increases in Sleep-like Activity.

Emotion self-regulation relies both on cognitive and behavioral strategies implemented to modulate the subjective experience and/or the behavioral expression of a given emotion. Although it is known that a network encompassing fronto-cingulate and parietal brain areas is engaged during successful emotion regulation, the functional mechanisms underlying failures in emotion suppression (ES) are still unclear. In order to investigate this issue, we analyzed video and high-density EEG recordings of 20 healthy adult participants during an ES and a free expression task performed on two consecutive days. Changes in facial expression during ES, but not free expression, were preceded by local increases in sleep-like activity (1-4 Hz) in brain areas responsible for emotional suppression, including bilateral anterior insula and anterior cingulate cortex, and in right middle/inferior frontal gyrus (p < .05, corrected). Moreover, shorter sleep duration the night before the ES experiment correlated with the number of behavioral errors (p = .03) and tended to be associated with higher frontal sleep-like activity during ES failures (p = .09). These results indicate that local sleep-like activity may represent the cause of ES failures in humans and may offer a functional explanation for previous observations linking lack of sleep, changes in frontal activity, and emotional dysregulation.

Complementing canonical fMRI with functional Quantitative Susceptibility Mapping (fQSM) in modern neuroimaging research.

Functional Quantitative Susceptibility Mapping (fQSM) allows for the quantitative measurement of time-varying magnetic susceptibility across cortical and subcortical brain structures with a potentially higher spatial specificity than conventional fMRI. While the usefulness of fQSM with General Linear Model and "On/Off" paradigms has been assessed, little is known about the potential applications and limitations of this technique in more sophisticated experimental paradigms and analyses, such as those currently used in modern neuroimaging. To thoroughly characterize fQSM activations, here we used 7T MRI, tonotopic mapping, as well as univariate (i.e., GLM and population Receptive Field) and multivariate (Representational Similarity Analysis; RSA) analyses. Although fQSM detected less tone-responsive voxels than fMRI, they were more consistently localized in gray matter. Also, the majority of active gray matter voxels exhibited negative fQSM response, signaling the expected oxyhemoglobin increase, whereas positive fQSM activations were mainly in white matter. Though fMRI- and fQSM-based tonotopic maps were overall comparable, the representation of frequency tunings in tone-sensitive regions was significantly more balanced for fQSM. Lastly, RSA revealed that frequency information from the auditory cortex could be successfully retrieved by using either methods. Overall, fQSM produces complementary results to conventional fMRI, as it captures small-scale variations in the activation pattern which inform multivariate measures. Although positive fQSM responses deserve further investigation, they do not impair the interpretation of contrasts of interest. The quantitative nature of fQSM, its spatial specificity and the possibility to simultaneously acquire canonical fMRI support the use of this technique for longitudinal and multicentric studies and pre-surgical mapping.

The case for preregistering all region of interest (ROI) analyses in neuroimaging research.

In neuroimaging studies, small sample sizes and the resultant reduced statistical power to detect effects that are not large, combined with inadequate analytic choices, concur to produce inflated or false-positive findings. To mitigate these issues, researchers often restrict analyses to specific brain areas, using the region of interest (ROI) approach. Crucially, ROI analysis assumes the a priori justified definition of the target region. Nonetheless, reports often lack details about where in the timeline, ranging from study conception to the data analysis and interpretation of findings, were ROIs selected. Frequently, the rationale for ROI selection is vague or inadequately founded on the existing literature. These shortcomings have important implications for ROI-based studies, augmenting the risk that observed effects are inflated or even false positives. Tools like preregistration and registered reports could address this problem, ensuring the validity of ROI-based studies. The benefits could be enhanced by additional practices such as selection of ROIs using quantitative methods (i.e., meta-analysis) and the sharing of whole-brain unthresholded maps of effect size, as well as of binary ROIs, in publicly accessible repositories.

Shape coding in occipito-temporal cortex relies on object silhouette, curvature, and medial axis.

Object recognition relies on different transformations of the retinal input, carried out by the visual system, that range from local contrast to object shape and category. While some of those transformations are thought to occur at specific stages of the visual hierarchy, the features they represent are correlated (e.g., object shape and identity) and selectivity for the same feature overlaps in many brain regions. This may be explained either by collinearity across representations or may instead reflect the coding of multiple dimensions by the same cortical population. Moreover, orthogonal and shared components may differently impact distinctive stages of the visual hierarchy. We recorded functional MRI activity while participants passively attended to object images and employed a statistical approach that partitioned orthogonal and shared object representations to reveal their relative impact on brain processing. Orthogonal shape representations (silhouette, curvature, and medial axis) independently explained distinct and overlapping clusters of selectivity in the occitotemporal and parietal cortex. Moreover, we show that the relevance of shared representations linearly increases moving from posterior to anterior regions. These results indicate that the visual cortex encodes shared relations between different features in a topographic fashion and that object shape is encoded along different dimensions, each representing orthogonal features.NEW & NOTEWORTHY There are several possible ways of characterizing the shape of an object. Which shape description better describes our brain responses while we passively perceive objects? Here, we employed three competing shape models to explain brain representations when viewing real objects. We found that object shape is encoded in a multidimensional fashion and thus defined by the interaction of multiple features.

Reductions in perceived stress following Transcendental Meditation practice are associated with increased brain regional connectivity at rest.

Transcendental Meditation (TM) is defined as a mental process of transcending using a silent mantra. Previous work showed that relatively brief period of TM practice leads to decreases in stress and anxiety. However, whether these changes are subserved by specific morpho-functional brain modifications (as observed in other meditation techniques) is still unclear. Using a longitudinal design, we combined psychometric questionnaires, structural and resting-state functional magnetic resonance imaging (RS-fMRI) to investigate the potential brain modifications underlying the psychological effects of TM. The final sample included 19 naïve subjects instructed to complete two daily 20-min TM sessions, and 15 volunteers in the control group. Both groups were evaluated at recruitment (T0) and after 3 months (T1). At T1, only meditators showed a decrease in perceived anxiety and stress (t(18) = 2.53, p = 0.02), which correlated negatively with T1-T0 changes in functional connectivity among posterior cingulate cortex (PCC), precuneus and left superior parietal lobule. Additionally, TM practice was associated with increased connectivity between PCC and right insula, likely reflecting changes in interoceptive awareness. No structural changes were observed in meditators or control subjects. These preliminary findings indicate that beneficial effects of TM may be mediated by functional brain changes that take place after a short practice period of 3 months.

To Move or Not to Move? Functional Role of Ventral Premotor Cortex in Motor Monitoring During Limb Immobilization.

Anatomo-clinical evidence from motor-awareness disorders after brain-damages suggests that the premotor cortex (PMC) is involved in motor-monitoring of voluntary actions. Indeed, PMC lesions prevent patients from detecting the mismatch between intended, but not executed, movements with the paralyzed limb. This functional magnetic resonance imaging study compared, in healthy subjects, free movements against blocked movements, precluded by a cast. Cast-related corticospinal excitability changes were investigated by using transcranial magnetic stimulation. Immediately after the immobilization, when the cast prevented the execution of left-hand movements, the contralateral right (ventral) vPMC showed both increased hemodynamic activity and increased functional connectivity with the hand area in the right somatosensory cortex, suggesting a vPMC involvement in detecting the mismatch between planned and executed movements. Crucially, after 1 week of immobilization, when the motor system had likely learned that no movement could be executed and, therefore, predictions about motor consequences were changed, vPMC did not show the enhanced activity as if no incongruence has to be detected. This can be interpreted as a consequence of the plastic changes induced by long-lasting immobilization, as also proved by the cast-related corticospinal excitability modulation in our subjects. The present findings highlight the crucial role of vPMC in the anatomo-functional network generating the human motor-awareness.

ROI and phobias: The effect of ROI approach on an ALE meta-analysis of specific phobias.

About 90% of fMRI findings on specific phobias (SP) include analysis of region of interest (ROI). This approach characterized by higher sensitivity may produce inflated results, particularly when findings are aggregated in meta-analytic maps. Here, we conducted a systematic review and activation likelihood estimation (ALE) meta-analysis on SP, testing the impact of the inclusion of ROI-based studies. ALE meta-analyses were carried out either including ROI-based results or focusing on whole-brain voxelwise studies exclusively. To assess the risk of bias in the neuroimaging field, we modified the Newcastle-Ottawa Scale (NOS) and measured the reliability of fMRI findings. Of the 31 selected investigations (564 patients and 485 controls) one-third did not motivate ROI selection: five studies did not report an explicit rationale, whereas four did not cite any specific reference in this regard. Analyses including ROI-based studies revealed differences between phobics and healthy subjects in several regions of the limbic circuit. However, when focusing on whole-brain analysis, only the anterior midcingulate cortex differentiated SP from controls. Notably, 13 studies were labeled with low risk of bias according to the adapted NOS. The inclusion of ROI-based results artificially inflates group differences in fMRI meta-analyses. Moreover, a priori, well-motivated selection of ROIs is desirable to improve quality and reproducibility in SP neuroimaging studies. Lastly, the use of modified NOS may represent a valuable way to assess and evaluate biases in fMRI studies: "low risk" of bias was reported for less than half of the included studies, indicating the need for better practices in fMRI.

Brain Hemodynamic Intermediate Phenotype Links Vitamin B12 to Cognitive Profile of Healthy and Mild Cognitive Impaired Subjects.

Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0.05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0.0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.

How concepts are encoded in the human brain: A modality independent, category-based cortical organization of semantic knowledge.

How conceptual knowledge is represented in the human brain remains to be determined. To address the differential role of low-level sensory-based and high-level abstract features in semantic processing, we combined behavioral studies of linguistic production and brain activity measures by functional magnetic resonance imaging in sighted and congenitally blind individuals while they performed a property-generation task with concrete nouns from eight categories, presented through visual and/or auditory modalities. Patterns of neural activity within a large semantic cortical network that comprised parahippocampal, lateral occipital, temporo-parieto-occipital and inferior parietal cortices correlated with linguistic production and were independent both from the modality of stimulus presentation (either visual or auditory) and the (lack of) visual experience. In contrast, selected modality-dependent differences were observed only when the analysis was limited to the individual regions within the semantic cortical network. We conclude that conceptual knowledge in the human brain relies on a distributed, modality-independent cortical representation that integrates the partial category and modality specific information retained at a regional level.

Sleep reverts changes in human gray and white matter caused by wake-dependent training.

Learning leads to rapid microstructural changes in gray (GM) and white (WM) matter. Do these changes continue to accumulate if task training continues, and can they be reverted by sleep? We addressed these questions by combining structural and diffusion weighted MRI and high-density EEG in 16 subjects studied during the physiological sleep/wake cycle, after 12 h and 24 h of intense practice in two different tasks, and after post-training sleep. Compared to baseline wake, 12 h of training led to a decline in cortical mean diffusivity. The decrease became even more significant after 24 h of task practice combined with sleep deprivation. Prolonged practice also resulted in decreased ventricular volume and increased GM and WM subcortical volumes. All changes reverted after recovery sleep. Moreover, these structural alterations predicted cognitive performance at the individual level, suggesting that sleep's ability to counteract performance deficits is linked to its effects on the brain microstructure. The cellular mechanisms that account for the structural effects of sleep are unknown, but they may be linked to its role in promoting the production of cerebrospinal fluid and the decrease in synapse size and strength, as well as to its recently discovered ability to enhance the extracellular space and the clearance of brain metabolites.

Progression from Vegetative to Minimally Conscious State Is Associated with Changes in Brain Neural Response to Passive Tasks: A Longitudinal Single-Case Functional MRI Study.

OBJECTIVES: Functional magnetic resonance imaging (fMRI) may be adopted as a complementary tool for bedside observation in the disorders of consciousness (DOC). However, the diagnostic value of this technique is still debated because of the lack of accuracy in determining levels of consciousness within a single patient. Recently, Giacino and colleagues (2014) hypothesized that a longitudinal fMRI evaluation may provide a more informative assessment in the detection of residual awareness. The aim of this study was to measure the correspondence between clinically defined level of awareness and neural responses within a single DOC patient. METHODS: We used a follow-up fMRI design in combination with a passive speech-processing task. Patient's consciousness was measured through time by using the Coma Recovery Scale. RESULTS: The patient progressed from a vegetative state (VS) to a minimally conscious state (MCS). Patient's task-related neural responses mirrored the clinical change from a VS to an MCS. Specifically, while in an MCS, but not a VS, the patient showed a selective recruitment of the left angular gyrus when he listened to a native speech narrative, as compared to the reverse presentation of the same stimulus. Furthermore, the patient showed an increased response in the language-related brain network and a greater deactivation in the default mode network following his progression to an MCS. CONCLUSIONS: Our findings indicate that longitudinal assessment of brain responses to passive stimuli can contribute to the definition of the clinical status in individual patients with DOC and represents an adequate counterpart of the bedside assessment during the diagnostic decision-making process. (JINS, 2016, 22, 620-630).

Machine learning and the prediction of suicide in psychiatric populations: a systematic review.

Machine learning (ML) has emerged as a promising tool to enhance suicidal prediction. However, as many large-sample studies mixed psychiatric and non-psychiatric populations, a formal psychiatric diagnosis emerged as a strong predictor of suicidal risk, overshadowing more subtle risk factors specific to distinct populations. To overcome this limitation, we conducted a systematic review of ML studies evaluating suicidal behaviors exclusively in psychiatric clinical populations. A systematic literature search was performed from inception through November 17, 2022 on PubMed, EMBASE, and Scopus following the PRISMA guidelines. Original research using ML techniques to assess the risk of suicide or predict suicide attempts in the psychiatric population were included. An assessment for bias risk was performed using the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines. About 1032 studies were retrieved, and 81 satisfied the inclusion criteria and were included for qualitative synthesis. Clinical and demographic features were the most frequently employed and random forest, support vector machine, and convolutional neural network performed better in terms of accuracy than other algorithms when directly compared. Despite heterogeneity in procedures, most studies reported an accuracy of 70% or greater based on features such as previous attempts, severity of the disorder, and pharmacological treatments. Although the evidence reported is promising, ML algorithms for suicidal prediction still present limitations, including the lack of neurobiological and imaging data and the lack of external validation samples. Overcoming these issues may lead to the development of models to adopt in clinical practice. Further research is warranted to boost a field that holds the potential to critically impact suicide mortality.

Virtual Reality Exposure Therapy for Treating Fear of Contamination Disorders: A Systematic Review of Healthy and Clinical Populations.

Virtual Reality Exposure Therapy (VRET), particularly immersive Virtual Reality Exposure Therapy (iVRET), has gained attraction as an innovative approach in exposure therapy (ET), notably for some anxiety disorders with a fear of contamination component, such as spider phobia (SP) and obsessive-compulsive disorder (OCD). This systematic work investigates iVRET's effectiveness in modulating disgust emotion-a shared aberrant feature across these disorders. Recent reviews have evaluated VRET's efficacy against in vivo ET. However, emerging evidence also highlights iVRET's potential in diminishing atypical disgust and related avoidance behaviors, expanding beyond traditional fear-focused outcomes. Our systematic synthesis, adhering to PRISMA guidelines, aims to fill this gap by assessing iVRET's efficacy in regulating disgust emotion within both clinical and at-risk populations, identified through standardized questionnaires and subjective disgust ratings. This research analyzes data from eight studies on clinical populations and five on healthy populations, offering an insight into iVRET's potential to mitigate the aberrant disgust response, a common transdiagnostic feature in varied psychopathologies. The findings support iVRET's clinical relevance in disgust management, providing evidence for a broader therapeutic application of iVRET and pointing out the need for more focused and complete investigations in this emergent field.

Evolution of Severe Closed Head Injury: Assessing Ventricular Volume and Behavioral Measures at 30 and 90 Days Post-Injury.

Background: Assessing functional outcomes in Severe Closed Head Injury (SCHI) is complex due to brain parenchymal changes. This study examines the Ventricles to Intracranial Volume Ratio (VBR) as a metric for these changes and its correlation with behavioral scales. Methods: Thirty-one SCHI patients were included. VBR was derived from CT scans at 3, 30, and 90 days post-injury and compared with Levels of Cognitive Functioning (LCF), Disability Rating Scale (DRS), and Early Rehabilitation Barthel Index (ERBI) assessments at 30 and 90 days. Results: Ten patients were excluded post-decompressive craniectomy or ventriculoperitoneal shunt. Findings indicated a VBR decrease at 3 days, suggesting acute phase compression, followed by an increase from 30 to 90 days, indicative of post-acute brain atrophy. VBR correlated positively with the Marshall score in the initial 72 h, positioning it as an early indicator of subsequent brain atrophy. Nevertheless, in contrast to the Marshall score, VBR had stronger associations with DRS and ERBI at 90 days. Conclusions: VBR, alongside behavioral assessments, presents a robust framework for evaluating SCHI progression. It supports early functional outcome correlations informing therapeutic approaches. VBR's reliability underscores its utility in neurorehabilitation for ongoing SCHI assessment and aiding clinical decisions.

Dissecting abstract, modality-specific and experience-dependent coding of affect in the human brain.

Emotion and perception are tightly intertwined, as affective experiences often arise from the appraisal of sensory information. Nonetheless, whether the brain encodes emotional instances using a sensory-specific code or in a more abstract manner is unclear. Here, we answer this question by measuring the association between emotion ratings collected during a unisensory or multisensory presentation of a full-length movie and brain activity recorded in typically developed, congenitally blind and congenitally deaf participants. Emotional instances are encoded in a vast network encompassing sensory, prefrontal, and temporal cortices. Within this network, the ventromedial prefrontal cortex stores a categorical representation of emotion independent of modality and previous sensory experience, and the posterior superior temporal cortex maps the valence dimension using an abstract code. Sensory experience more than modality affects how the brain organizes emotional information outside supramodal regions, suggesting the existence of a scaffold for the representation of emotional states where sensory inputs during development shape its functioning.

Optimal encoding of interval timing in expert percussionists.

We measured temporal reproduction in human subjects with various levels of musical expertise: expert drummers, string musicians, and non-musicians. While duration reproduction of the non-percussionists showed a characteristic central tendency or regression to the mean, drummers responded veridically. Furthermore, when the stimuli were auditory tones rather than flashes, all subjects responded veridically. The behavior of all three groups in both modalities is well explained by a Bayesian model that seeks to minimize reproduction errors by incorporating a central tendency prior, a probability density function centered at the mean duration of the sample. We measured separately temporal precision thresholds with a bisection task; thresholds were twice as low in drummers as in the other two groups. These estimates of temporal precision, together with an adaptable Bayesian prior, predict well the reproduction results and the central tendency strategy under all conditions and for all subject groups. These results highlight the efficiency and flexibility of sensorimotor mechanisms estimating temporal duration.

Megakaryocytes differentially sort mRNAs for matrix metalloproteinases and their inhibitors into platelets: a mechanism for regulating synthetic events.

Megakaryocytes transfer a diverse and functional transcriptome to platelets during the final stages of thrombopoiesis. In platelets, these transcripts reflect the expression of their corresponding proteins and, in some cases, serve as a template for translation. It is not known, however, if megakaryocytes differentially sort mRNAs into platelets. Given their critical role in vascular remodeling and inflammation, we determined whether megakaryocytes selectively dispense transcripts for matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) into platelets. Next-generation sequencing (RNA-Seq) revealed that megakaryocytes express mRNA for 10 of the 24 human MMP family members. mRNA for all of these MMPs are present in platelets with the exception of MMP-2, 14, and 15. Megakaryocytes and platelets also express mRNA for TIMPs 1-3, but not TIMP-4. mRNA expression patterns predicted the presence and, in most cases, the abundance of each corresponding protein. Nonetheless, exceptions were observed: MMP-2 protein is present in platelets but not its transcript. In contrast, quiescent platelets express TIMP-2 mRNA but only traces of TIMP-2 protein. In response to activating signals, however, platelets synthesize significant amounts of TIMP-2 protein. These results demonstrate that megakaryocytes differentially express mRNAs for MMPs and TIMPs and selectively transfer a subset of these into platelets. Among the platelet messages, TIMP-2 serves as a template for signal-dependent translation.