Functional connectivity development along the sensorimotor-association axis enhances the cortical hierarchy.

Human cortical maturation has been posited to be organized along the sensorimotor-association axis, a hierarchical axis of brain organization that spans from unimodal sensorimotor cortices to transmodal association cortices. Here, we investigate the hypothesis that the development of functional connectivity during childhood through adolescence conforms to the cortical hierarchy defined by the sensorimotor-association axis. We tested this pre-registered hypothesis in four large-scale, independent datasets (total n = 3355; ages 5-23 years): the Philadelphia Neurodevelopmental Cohort (n = 1207), Nathan Kline Institute-Rockland Sample (n = 397), Human Connectome Project: Development (n = 625), and Healthy Brain Network (n = 1126). Across datasets, the development of functional connectivity systematically varied along the sensorimotor-association axis. Connectivity in sensorimotor regions increased, whereas connectivity in association cortices declined, refining and reinforcing the cortical hierarchy. These consistent and generalizable results establish that the sensorimotor-association axis of cortical organization encodes the dominant pattern of functional connectivity development.

Generalizable Links Between Borderline Personality Traits and Functional Connectivity.

BACKGROUND: Symptoms of borderline personality disorder (BPD) often manifest during adolescence, but the underlying relationship between these debilitating symptoms and the development of functional brain networks is not well understood. Here, we aimed to investigate how multivariate patterns of functional connectivity are associated with borderline personality traits in large samples of young adults and adolescents. METHODS: We used functional magnetic resonance imaging data from young adults and adolescents from the HCP-YA (Human Connectome Project Young Adult) (n = 870, ages 22-37 years, 457 female) and the HCP-D (Human Connectome Project Development) (n = 223, ages 16-21 years, 121 female). A previously validated BPD proxy score was derived from the NEO Five-Factor Inventory. A ridge regression model with cross-validation and nested hyperparameter tuning was trained and tested in HCP-YA to predict BPD scores in unseen data from regional functional connectivity. The trained model was further tested on data from HCP-D without further tuning. Finally, we tested how the connectivity patterns associated with BPD aligned with age-related changes in connectivity. RESULTS: Multivariate functional connectivity patterns significantly predicted out-of-sample BPD scores in unseen data in young adults (HCP-YA ppermuted = .001) and older adolescents (HCP-D ppermuted = .001). Regional predictive capacity was heterogeneous; the most predictive regions were found in functional systems relevant for emotion regulation and executive function, including the ventral attention network. Finally, regional functional connectivity patterns that predicted BPD scores aligned with those associated with development in youth. CONCLUSIONS: Individual differences in functional connectivity in developmentally sensitive regions are associated with borderline personality traits.

Framewise multi-echo distortion correction for superior functional MRI.

Functional MRI (fMRI) data are severely distorted by magnetic field (B0) inhomogeneities which currently must be corrected using separately acquired field map data. However, changes in the head position of a scanning participant across fMRI frames can cause changes in the B0 field, preventing accurate correction of geometric distortions. Additionally, field maps can be corrupted by movement during their acquisition, preventing distortion correction altogether. In this study, we use phase information from multi-echo (ME) fMRI data to dynamically sample distortion due to fluctuating B0 field inhomogeneity across frames by acquiring multiple echoes during a single EPI readout. Our distortion correction approach, MEDIC (Multi-Echo DIstortion Correction), accurately estimates B0 related distortions for each frame of multi-echo fMRI data. Here, we demonstrate that MEDIC's framewise distortion correction produces improved alignment to anatomy and decreases the impact of head motion on resting-state functional connectivity (RSFC) maps, in higher motion data, when compared to the prior gold standard approach (i.e., TOPUP). Enhanced framewise distortion correction with MEDIC, without the requirement for field map collection, furthers the advantage of multi-echo over single-echo fMRI.

XCP-D: A Robust Pipeline for the post-processing of fMRI data.

Functional neuroimaging is an essential tool for neuroscience research. Pre-processing pipelines produce standardized, minimally pre-processed data to support a range of potential analyses. However, post-processing is not similarly standardized. While several options for post-processing exist, they tend not to support output from disparate pre-processing pipelines, may have limited documentation, and may not follow BIDS best practices. Here we present XCP-D, which presents a solution to these issues. XCP-D is a collaborative effort between PennLINC at the University of Pennsylvania and the DCAN lab at the University at Minnesota. XCP-D uses an open development model on GitHub and incorporates continuous integration testing; it is distributed as a Docker container or Singularity image. XCP-D generates denoised BOLD images and functional derivatives from resting-state data in either NifTI or CIFTI files, following pre-processing with fMRIPrep, HCP, and ABCD-BIDS pipelines. Even prior to its official release, XCP-D has been downloaded >3,000 times from DockerHub. Together, XCP-D facilitates robust, scalable, and reproducible post-processing of fMRI data.

Graded functional organization in the left inferior frontal gyrus: evidence from task-free and task-based functional connectivity.

The left inferior frontal gyrus has been ascribed key roles in numerous cognitive domains, such as language and executive function. However, its functional organization is unclear. Possibilities include a singular domain-general function, or multiple functions that can be mapped onto distinct subregions. Furthermore, spatial transition in function may be either abrupt or graded. The present study explored the topographical organization of the left inferior frontal gyrus using a bimodal data-driven approach. We extracted functional connectivity gradients from (i) resting-state fMRI time-series and (ii) coactivation patterns derived meta-analytically from heterogenous sets of task data. We then sought to characterize the functional connectivity differences underpinning these gradients with seed-based resting-state functional connectivity, meta-analytic coactivation modeling and functional decoding analyses. Both analytic approaches converged on graded functional connectivity changes along 2 main organizational axes. An anterior-posterior gradient shifted from being preferentially associated with high-level control networks (anterior functional connectivity) to being more tightly coupled with perceptually driven networks (posterior). A second dorsal-ventral axis was characterized by higher connectivity with domain-general control networks on one hand (dorsal functional connectivity), and with the semantic network, on the other (ventral). These results provide novel insights into an overarching graded functional organization of the functional connectivity that explains its role in multiple cognitive domains.

Acculturative Orientations Among Hispanic/Latinx Caregivers in the ABCD Study: Associations With Caregiver and Youth Mental Health and Youth Brain Function.

Background: Population-based neuroscience offers opportunities to examine important but understudied sociocultural factors such as acculturation. Acculturation refers to the extent to which an individual retains their cultural heritage and/or adopts the receiving society's culture and is particularly salient among Hispanic/Latinx immigrants. Specific acculturative orientations have been linked to vulnerability to substance use, depression, and suicide and are known to influence family dynamics between caregivers and their children. Methods: Using data from first- and second-generation Hispanic/Latinx caregivers in the Adolescent Brain Cognitive Development (ABCD) Study (N = 1057), we examined how caregivers' acculturative orientation affects their mental health, as well as the mental health and brain function of their children. Neuroimaging analyses focused on regions associated with self- and affiliation-based social processing (ventromedial prefrontal cortex, insula, and temporoparietal junction). Results: We identified 2 profiles of caregiver acculturation: bicultural (retains heritage culture while adopting U.S. culture) and detached (discards heritage culture and rejects U.S. culture). Bicultural caregivers exhibited fewer internalizing and externalizing problems than detached caregivers; furthermore, youth exhibited similar internalizing effects across caregiver profiles. In addition, youth with bicultural caregivers displayed increased resting-state brain activity (i.e., fractional amplitude of low-frequency fluctuations and regional homogeneity) in the left insula, which has been linked to psychopathology; however, differences in long-range functional connectivity were not significant. Conclusions: Caregiver acculturation is an important familial factor that has been linked to significant differences in youth mental health and insula activity. Future work should examine sociocultural and neurodevelopmental changes across adolescence to assess health outcomes and determine whether localized, corticolimbic brain effects are ultimately translated into long-range connectivity differences.

Generalizable links between symptoms of borderline personality disorder and functional connectivity.

Background |: Symptoms of borderline personality disorder (BPD) often manifest in adolescence, yet the underlying relationship between these debilitating symptoms and the development of functional brain networks is not well understood. Here we aimed to investigate how multivariate patterns of functional connectivity are associated with symptoms of BPD in a large sample of young adults and adolescents. Methods |: We used high-quality functional Magnetic Resonance Imaging (fMRI) data from young adults from the Human Connectome Project: Young Adults (HCP-YA; N = 870, ages 22-37 years, 457 female) and youth from the Human Connectome Project: Development (HCP-D; N = 223, age range 16-21 years, 121 female). A previously validated BPD proxy score was derived from the NEO Five Factor Inventory (NEO-FFI). A ridge regression model with 10-fold cross-validation and nested hyperparameter tuning was trained and tested in HCP-YA to predict BPD scores in unseen data from regional functional connectivity, while controlling for in-scanner motion, age, and sex. The trained model was further tested on data from HCP-D without further tuning. Finally, we tested how the connectivity patterns associated with BPD aligned with age-related changes in connectivity. Results |: Multivariate functional connectivity patterns significantly predicted out-of-sample BPD proxy scores in unseen data in both young adults (HCP-YA; pperm = 0.001) and older adolescents (HCP-D; pperm = 0.001). Predictive capacity of regions was heterogeneous; the most predictive regions were found in functional systems relevant for emotion regulation and executive function, including the ventral attention network. Finally, regional functional connectivity patterns that predicted BPD proxy scores aligned with those associated with development in youth. Conclusion |: Individual differences in functional connectivity in developmentally-sensitive regions are associated with the symptoms of BPD.

Task-based attentional and default mode connectivity associated with science and math anxiety profiles among university physics students.

PURPOSE: Attentional control theory (ACT) posits that elevated anxiety increases the probability of re-allocating cognitive resources needed to complete a task to processing anxiety-related stimuli. This process impairs processing efficiency and can lead to reduced performance effectiveness. Science, technology, engineering, and math (STEM) students frequently experience anxiety about their coursework, which can interfere with learning and performance and negatively impact student retention and graduation rates. The objective of this study was to extend the ACT framework to investigate the neurobiological associations between science and math anxiety and cognitive performance among 123 physics undergraduate students. PROCEDURES: Latent profile analysis (LPA) identified four profiles of science and math anxiety among STEM students, including two profiles that represented the majority of the sample (Low Science and Math Anxiety; 59.3% and High Math Anxiety; 21.9%) and two additional profiles that were not well represented (High Science and Math Anxiety; 6.5% and High Science Anxiety; 4.1%). Students underwent a functional magnetic resonance imaging (fMRI) session in which they performed two tasks involving physics cognition: the Force Concept Inventory (FCI) task and the Physics Knowledge (PK) task. FINDINGS: No significant differences were observed in FCI or PK task performance between High Math Anxiety and Low Science and Math Anxiety students. During the three phases of the FCI task, we found no significant brain connectivity differences during scenario and question presentation, yet we observed significant differences during answer selection within and between the dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN). Further, we found significant group differences during the PK task were limited to the DAN, including DAN-VAN and within-DAN connectivity. CONCLUSIONS: These results highlight the different cognitive processes required for physics conceptual reasoning compared to physics knowledge retrieval, provide new insight into the underlying brain dynamics associated with anxiety and physics cognition, and confirm the relevance of ACT theory for science and math anxiety.

Methods for decoding cortical gradients of functional connectivity.

Macroscale gradients have emerged as a central principle for understanding functional brain organization. Previous studies have demonstrated that a principal gradient of connectivity in the human brain exists, with unimodal primary sensorimotor regions situated at one end and transmodal regions associated with the default mode network and representative of abstract functioning at the other. The functional significance and interpretation of macroscale gradients remains a central topic of discussion in the neuroimaging community, with some studies demonstrating that gradients may be described using meta-analytic functional decoding techniques. However, additional methodological development is necessary to fully leverage available meta-analytic methods and resources and quantitatively evaluate their relative performance. Here, we conducted a comprehensive series of analyses to investigate and improve the framework of data-driven, meta-analytic methods, thereby establishing a principled approach for gradient segmentation and functional decoding. We found that a two-segment solution determined by a k-means segmentation approach and an LDA-based meta-analysis combined with the NeuroQuery database was the optimal combination of methods for decoding functional connectivity gradients. Finally, we proposed a method for decoding additional components of the gradient decomposition. The current work aims to provide recommendations on best practices and flexible methods for gradient-based functional decoding of fMRI data.

A reproducible and generalizable software workflow for analysis of large-scale neuroimaging data collections using BIDS Apps.

Neuroimaging research faces a crisis of reproducibility. With massive sample sizes and greater data complexity, this problem becomes more acute. Software that operates on imaging data defined using the Brain Imaging Data Structure (BIDS) - BIDS Apps - have provided a substantial advance. However, even using BIDS Apps, a full audit trail of data processing is a necessary prerequisite for fully reproducible research. Obtaining a faithful record of the audit trail is challenging - especially for large datasets. Recently, the FAIRly big framework was introduced as a way to facilitate reproducible processing of large-scale data by leveraging DataLad - a version control system for data management. However, the current implementation of this framework was more of a proof of concept, and could not be immediately reused by other investigators for different use cases. Here we introduce the BIDS App Bootstrap (BABS), a user-friendly and generalizable Python package for reproducible image processing at scale. BABS facilitates the reproducible application of BIDS Apps to large-scale datasets. Leveraging DataLad and the FAIRly big framework, BABS tracks the full audit trail of data processing in a scalable way by automatically preparing all scripts necessary for data processing and version tracking on high performance computing (HPC) systems. Currently, BABS supports jobs submissions and audits on Sun Grid Engine (SGE) and Slurm HPCs with a parsimonious set of programs. To demonstrate its scalability, we applied BABS to data from the Healthy Brain Network (HBN; n=2,565). Taken together, BABS allows reproducible and scalable image processing and is broadly extensible via an open-source development model.

Graded functional organisation in the left inferior frontal gyrus: evidence from task-free and task-based functional connectivity.

The left inferior frontal gyrus (LIFG) has been ascribed key roles in numerous cognitive domains, including language, executive function and social cognition. However, its functional organisation, and how the specific areas implicated in these cognitive domains relate to each other, is unclear. Possibilities include that the LIFG underpins a domain-general function or, alternatively, that it is characterized by functional differentiation, which might occur in either a discrete or a graded pattern. The aim of the present study was to explore the topographical organisation of the LIFG using a bimodal data-driven approach. To this end, we extracted functional connectivity (FC) gradients from 1) the resting-state fMRI time-series of 150 participants (77 female), and 2) patterns of co-activation derived meta-analytically from task data across a diverse set of cognitive domains. We then sought to characterize the FC differences driving these gradients with seed-based resting-state FC and meta-analytic co-activation modelling analyses. Both analytic approaches converged on an FC profile that shifted in a graded fashion along two main organisational axes. An anterior-posterior gradient shifted from being preferentially associated with high-level control networks (anterior LIFG) to being more tightly coupled with perceptually-driven networks (posterior). A second dorsal-ventral axis was characterized by higher connectivity with domain-general control networks on one hand (dorsal LIFG), and with the semantic network, on the other (ventral). These results provide novel insights into a graded functional organisation of the LIFG underpinning both task-free and task-constrained mental states, and suggest that the LIFG is an interface between distinct large-scale functional networks.

Neural systems underlying RDoC social constructs: An activation likelihood estimation meta-analysis.

Neuroscientists have sought to identify the underlying neural systems supporting social processing that allow interaction and communication, forming social relationships, and navigating the social world. Through the use of NIMH's Research Domain Criteria (RDoC) framework, we evaluated consensus among studies that examined brain activity during social tasks to elucidate regions comprising the "social brain". We examined convergence across tasks corresponding to the four RDoC social constructs, including Affiliation and Attachment, Social Communication, Perception and Understanding of Self, and Perception and Understanding of Others. We performed a series of coordinate-based meta-analyses using the activation likelihood estimate (ALE) method. Meta-analysis was performed on whole-brain coordinates reported from 864 fMRI contrasts using the NiMARE Python package, revealing convergence in medial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, temporoparietal junction, bilateral insula, amygdala, fusiform gyrus, precuneus, and thalamus. Additionally, four separate RDoC-based meta-analyses revealed differential convergence associated with the four social constructs. These outcomes highlight the neural support underlying these social constructs and inform future research on alterations among neurotypical and atypical populations.

Extended functional connectivity of convergent structural alterations among individuals with PTSD: a neuroimaging meta-analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a debilitating disorder defined by the onset of intrusive, avoidant, negative cognitive or affective, and/or hyperarousal symptoms after witnessing or experiencing a traumatic event. Previous voxel-based morphometry studies have provided insight into structural brain alterations associated with PTSD with notable heterogeneity across these studies. Furthermore, how structural alterations may be associated with brain function, as measured by task-free and task-based functional connectivity, remains to be elucidated. METHODS: Using emergent meta-analytic techniques, we sought to first identify a consensus of structural alterations in PTSD using the anatomical likelihood estimation (ALE) approach. Next, we generated functional profiles of identified convergent structural regions utilizing resting-state functional connectivity (rsFC) and meta-analytic co-activation modeling (MACM) methods. Finally, we performed functional decoding to examine mental functions associated with our ALE, rsFC, and MACM brain characterizations. RESULTS: We observed convergent structural alterations in a single region located in the medial prefrontal cortex. The resultant rsFC and MACM maps identified functional connectivity across a widespread, whole-brain network that included frontoparietal and limbic regions. Functional decoding revealed overlapping associations with attention, memory, and emotion processes. CONCLUSIONS: Consensus-based functional connectivity was observed in regions of the default mode, salience, and central executive networks, which play a role in the tripartite model of psychopathology. Taken together, these findings have important implications for understanding the neurobiological mechanisms associated with PTSD.

Convergent gray matter alterations across drugs of abuse and network-level implications: A meta-analysis of structural MRI studies.

BACKGROUND: Neuroimaging studies often consider brain alterations linked with substance abuse within the context of individual drugs (e.g., nicotine), while neurobiological theories of addiction emphasize common brain network-level alterations across drug classes. Using emergent meta-analytic techniques, we identified common structural brain alterations across drugs and characterized the functionally-connected networks with which such structurally altered regions interact. METHODS: We identified 82 articles characterizing gray matter (GM) volume differences for substance users vs. controls. Using the anatomical likelihood estimation algorithm, we identified convergent GM reductions across drug classes. Next, we performed resting-state and meta-analytic functional connectivity analyses using each structurally altered region as a seed and computed whole-brain functional connectivity profiles as the union of both maps. We characterized an "extended network" by identifying brain areas demonstrating the highest degree of functional coupling with structurally impacted regions. Finally, hierarchical clustering was performed leveraging extended network nodes' functional connectivity profiles to delineate subnetworks. RESULTS: Across drug classes, we identified medial frontal/ventromedial prefrontal, and multiple regions in anterior cingulate (ACC) and insula as regions displaying convergent GM reductions among users. Overlap of these regions' functional connectivity profiles identified ACC, inferior frontal, PCC, insula, superior temporal, and putamen as regions of an impacted extended network. Hierarchical clustering revealed 3 subnetworks closely corresponding to default mode (PCC, angular), salience (dACC, caudate), and executive control networks (dlPFC and parietal). CONCLUSIONS: These outcomes suggest that substance-related structural brain alterations likely have implications for the functioning of canonical large-scale networks and the perpetuation of substance use and neurocognitive alterations.

qMRI-BIDS: An extension to the brain imaging data structure for quantitative magnetic resonance imaging data.

The Brain Imaging Data Structure (BIDS) established community consensus on the organization of data and metadata for several neuroimaging modalities. Traditionally, BIDS had a strong focus on functional magnetic resonance imaging (MRI) datasets and lacked guidance on how to store multimodal structural MRI datasets. Here, we present and describe the BIDS Extension Proposal 001 (BEP001), which adds a range of quantitative MRI (qMRI) applications to the BIDS. In general, the aim of qMRI is to characterize brain microstructure by quantifying the physical MR parameters of the tissue via computational, biophysical models. By proposing this new standard, we envision standardization of qMRI through multicenter dissemination of interoperable datasets. This way, BIDS can act as a catalyst of convergence between qMRI methods development and application-driven neuroimaging studies that can help develop quantitative biomarkers for neural tissue characterization. In conclusion, this BIDS extension offers a common ground for developers to exchange novel imaging data and tools, reducing the entrance barrier for qMRI in the field of neuroimaging.

Risky decision-making strategies mediate the relationship between amygdala activity and real-world financial savings among individuals from lower income households: A pilot study.

Lower financial savings among individuals experiencing adverse social determinants of health (SDoH) increases vulnerabilities during times of crisis. SDoH including low socioeconomic status (low-SES) influence cognitive abilities as well as health and life outcomes that may perpetuate poverty and disparities. Despite evidence suggesting a role for financial growth in minimizing SDoH-related disparities and vulnerabilities, neurobiological mechanisms linked with financial behavior remain to be elucidated. As such, we examined the relationships between brain activity during decision-making (DM), laboratory-based task performance, and money savings behavior. Participants (N = 24, 14 females) from low-SES households (income<$20,000/year) underwent fMRI scanning while performing the Balloon Analogue Risk Task (BART), a DM paradigm probing risky- and strategic-DM processes. Participants also completed self-report instruments characterizing relevant personality characteristics and then engaged in a community outreach financial program where amount of money saved was tracked over a 6-month period. Regarding BART-related brain activity, we observed expected activity in regions implicated in reward and emotional processing including the amygdala. Regarding brain-behavior relationships, we found that laboratory-based BART performance mediated the impact of amygdala activity on real-world behavior. That is, elevated amygdala activity was linked with BART strategic-DM which, in turn, was linked with more money saved after 6 months. In exploratory analyses, this mediation was moderated by emotion-related personality characteristics such that, only individuals reporting lower alexithymia demonstrated a relationship between amygdala activity and savings. These outcomes suggest that DM-related amygdala activity and/or emotion-related personality characteristics may provide utility as an endophenotypic marker of individual's financial savings behavior.

Altered large-scale brain network interactions associated with HIV infection and error processing.

Altered activity within and between large-scale brain networks has been implicated across various neuropsychiatric conditions. However, patterns of network dysregulation associated with human immunodeficiency virus (HIV), and further impacted by cannabis (CB) use, remain to be delineated. We examined the impact of HIV and CB on resting-state functional connectivity (rsFC) between brain networks and associations with error awareness and error-related network responsivity. Participants (N = 106), stratified into four groups (HIV+/CB+, HIV+/CB-, HIV-/CB+, HIV-/CB-), underwent fMRI scanning while completing a resting-state scan and a modified Go/NoGo paradigm assessing brain responsivity to errors and explicit error awareness. We examined separate and interactive effects of HIV and CB on resource allocation indexes (RAIs), a measure quantifying rsFC strength between the default mode network (DMN), central executive network (CEN), and salience network (SN). We observed reduced RAIs among HIV+ (vs. HIV-) participants, which was driven by increased SN-DMN rsFC. No group differences were detected for SN-CEN rsFC. Increased SN-DMN rsFC correlated with diminished error awareness, but not with error-related network responsivity. These outcomes highlight altered network interactions among participants with HIV and suggest such rsFC dysregulation may persist during task performance, reflecting an inability to disengage irrelevant mental operations, ultimately hindering error processing.

Interactive Effects of HIV Infection and Cannabis Use on Insula Subregion Functional Connectivity.

Chronic inflammation in the central nervous system is one mechanism through which human immunodeficiency virus (HIV) may lead to progressive cognitive decline. Given cannabis's (CB's) anti-inflammatory properties, use prevalence among people living with HIV (PLWH), and evidence implicating the insula in both, we examined independent and interactive effects of HIV and CB on insular circuitry, cognition, and immune function. We assessed resting-state functional connectivity (rsFC) of three insula subregions among 106 participants across four groups (co-occurring: HIV+/CB+; HIV-only: HIV+/CB-; CB-only: HIV-/CB+; controls: HIV-/CB-). Participants completed a neurocognitive battery assessing functioning across multiple domains and self-reported somatic complaints. Blood samples quantified immune function (T-cell counts) and inflammation (tumor necrosis factor alpha [TNF-α]). We observed interactive HIV × CB effects on rsFC strength between two anterior insula (aI) subregions and sensorimotor cortices such that, CB appeared to normalize altered rsFC among non-using PLWH. Specifically, compared to controls, HIV-only and CB-only groups displayed decreased dorsal anterior insula (DI) - postcentral gyrus rsFC and increased ventral anterior insula (VI) - supplementary motor area rsFC, whereas the co-occurring group displayed DI and VI rsFC more akin to that of controls. Altered DI - postcentral rsFC correlated with decreased processing speed and somatic complaints, but did not significantly correlate with inflammation (TNF-α). These outcomes implicate insula - sensorimotor neurocircuitries in HIV and CB and are consistent with prior work suggesting that CB use may normalize insula functioning among PLWH.

The cue-reactivity paradigm: An ensemble of networks driving attention and cognition when viewing drug and natural reward-related stimuli.

The cue-reactivity paradigm is a widely adopted neuroimaging probe engendering brain activity linked with attentional, affective, and reward processes following presentation of appetitive stimuli. Given the multiple mental operations invoked, we sought to decompose cue-related brain activity into constituent components employing emergent meta-analytic techniques when considering drug and natural reward-related cues. We conducted coordinate-based meta-analyses delineating common and distinct brain activity convergence across cue-reactivity studies (N = 196 articles) involving drug (n = 133) or natural (n = 63) visual stimuli. Across all studies, convergence was observed in limbic, cingulate, insula, and fronto-parieto-occipital regions. Drug-distinct convergence was observed in posterior cingulate, dorsolateral prefrontal, and temporo-parietal regions, whereas distinct-natural convergence was observed in thalamic, insular, orbitofrontal, and occipital regions. We characterized connectivity profiles of identified regions by leveraging task-independent and task-dependent MRI datasets, grouped these profiles into subnetworks, and linked each with putative mental operations. Outcomes suggest multifaceted brain activity during cue-reactivity can be decomposed into elemental processes and indicate that while drugs of abuse usurp the brain's natural-reward-processing system, some regions appear distinct to drug cue-reactivity.