A network correspondence toolbox for quantitative evaluation of novel neuroimaging results.

Decades of neuroscience research has shown that macroscale brain dynamics can be reliably decomposed into a subset of large-scale functional networks, but the specific spatial topographies of these networks and the names used to describe them can vary across studies. Such discordance has hampered interpretation and convergence of research findings across the field. To address this problem, we have developed the Network Correspondence Toolbox (NCT) to permit researchers to examine and report spatial correspondence between their novel neuroimaging results and sixteen widely used functional brain atlases, consistent with recommended reporting standards developed by the Organization for Human Brain Mapping. The atlases included in the toolbox show some topographical convergence for specific networks, such as those labeled as default or visual. Network naming varies across atlases, particularly for networks spanning frontoparietal association cortices. For this reason, quantitative comparison with multiple atlases is recommended to benchmark novel neuroimaging findings. We provide several exemplar demonstrations using the Human Connectome Project task fMRI results and UK Biobank independent component analysis maps to illustrate how researchers can use the NCT to report their own findings through quantitative evaluation against multiple published atlases. The NCT provides a convenient means for computing Dice coefficients with spin test permutations to determine the magnitude and statistical significance of correspondence among user-defined maps and existing atlas labels. The NCT also includes functionality to incorporate additional atlases in the future. The adoption of the NCT will make it easier for network neuroscience researchers to report their findings in a standardized manner, thus aiding reproducibility and facilitating comparisons between studies to produce interdisciplinary insights.

Age-related differences in resting-state, task-related, and structural brain connectivity: graph theoretical analyses and visual search performance.

Previous magnetic resonance imaging (MRI) research suggests that aging is associated with a decrease in the functional interconnections within and between groups of locally organized brain regions (modules). Further, this age-related decrease in the segregation of modules appears to be more pronounced for a task, relative to a resting state, reflecting the integration of functional modules and attentional allocation necessary to support task performance. Here, using graph-theoretical analyses, we investigated age-related differences in a whole-brain measure of module connectivity, system segregation, for 68 healthy, community-dwelling individuals 18-78 years of age. We obtained resting-state, task-related (visual search), and structural (diffusion-weighted) MRI data. Using a parcellation of modules derived from the participants' resting-state functional MRI data, we demonstrated that the decrease in system segregation from rest to task (i.e., reconfiguration) increased with age, suggesting an age-related increase in the integration of modules required by the attentional demands of visual search. Structural system segregation increased with age, reflecting weaker connectivity both within and between modules. Functional and structural system segregation had qualitatively different influences on age-related decline in visual search performance. Functional system segregation (and reconfiguration) influenced age-related decline in the rate of visual evidence accumulation (drift rate), whereas structural system segregation contributed to age-related slowing of encoding and response processes (nondecision time). The age-related differences in the functional system segregation measures, however, were relatively independent of those associated with structural connectivity.

Controversies and progress on standardization of large-scale brain network nomenclature.

Progress in scientific disciplines is accompanied by standardization of terminology. Network neuroscience, at the level of macroscale organization of the brain, is beginning to confront the challenges associated with developing a taxonomy of its fundamental explanatory constructs. The Workgroup for HArmonized Taxonomy of NETworks (WHATNET) was formed in 2020 as an Organization for Human Brain Mapping (OHBM)-endorsed best practices committee to provide recommendations on points of consensus, identify open questions, and highlight areas of ongoing debate in the service of moving the field toward standardized reporting of network neuroscience results. The committee conducted a survey to catalog current practices in large-scale brain network nomenclature. A few well-known network names (e.g., default mode network) dominated responses to the survey, and a number of illuminating points of disagreement emerged. We summarize survey results and provide initial considerations and recommendations from the workgroup. This perspective piece includes a selective review of challenges to this enterprise, including (1) network scale, resolution, and hierarchies; (2) interindividual variability of networks; (3) dynamics and nonstationarity of networks; (4) consideration of network affiliations of subcortical structures; and (5) consideration of multimodal information. We close with minimal reporting guidelines for the cognitive and network neuroscience communities to adopt.

Brain tissue iron neurophysiology and its relationship with the cognitive effects of dopaminergic modulation in children with and without ADHD.

Children with attention-deficit/hyperactivity disorder (ADHD) exhibit impairments in response inhibition. These impairments are ameliorated by modulating dopamine (DA) via the administration of rewards or stimulant medication like methylphenidate (MPH). It is currently unclear whether intrinsic DA availability impacts these effects of dopaminergic modulation on response inhibition. Thus, we estimated intrinsic DA availability using magnetic resonance-based assessments of basal ganglia and thalamic tissue iron in 36 medication-naïve children with ADHD and 29 typically developing (TD) children (8-12 y) who underwent fMRI scans and completed standard and rewarded go/no-go tasks. Children with ADHD additionally participated in a double-blind, randomized, placebo-controlled, crossover MPH challenge. Using linear regressions covarying for age and sex, we determined there were no group differences in brain tissue iron. We additionally found that higher putamen tissue iron was associated with worse response inhibition performance in all participants. Crucially, we observed that higher putamen and caudate tissue iron was associated with greater responsivity to MPH, as measured by improved task performance, in participants with ADHD. These results begin to clarify the role of subcortical brain tissue iron, a measure associated with intrinsic DA availability, in the cognitive effects of reward- and MPH-related dopaminergic modulation in children with ADHD and TD children.

Modeling individual differences in the timing of change onset and offset.

Individual differences in the timing of developmental processes are often of interest in longitudinal studies, yet common statistical approaches to modeling change cannot directly estimate the timing of when change occurs. The time-to-criterion framework was recently developed to incorporate the timing of a prespecified criterion value; however, this framework has difficulty accommodating contexts where the criterion value differs across people or when the criterion value is not known a priori, such as when the interest is in individual differences in when change starts or stops. This article combines aspects of reparameterized quadratic models and multiphase models to provide information on the timing of change. We first consider the more common situation of modeling decelerating change to an offset point, defined as the point in time at which change ceases. For increasing trajectories, the offset occurs when the criterion attains its maximum ("inverted J-shaped" trajectories). For decreasing trajectories, offset instead occurs at the minimum. Our model allows for individual differences in both the timing of offset and ultimate level of the outcome. The same model, reparameterized slightly, captures accelerating change from a point of onset ("J-shaped" trajectories). We then extend the framework to accommodate "S-shaped" curves where both the onset and offset of change are within the observation window. We provide demonstrations that span neuroscience, educational psychology, developmental psychology, and cognitive science, illustrating the applicability of the modeling framework to a variety of research questions about individual differences in the timing of change. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effect of methylphenidate on functional controllability: a preliminary study in medication-naïve children with ADHD.

Methylphenidate (MPH) is the recommended first-line treatment for attention-deficit/hyperactivity disorder (ADHD). While MPH's mechanism of action as a dopamine and noradrenaline transporter blocker is well known, how this translates to ADHD-related symptom mitigation is still unclear. As functional connectivity is reliably altered in ADHD, with recent literature indicating dysfunctional connectivity dynamics as well, one possible mechanism is through altering brain network dynamics. In a double-blind, placebo-controlled MPH crossover trial, 19 medication-naïve children with ADHD underwent two functional MRI scanning sessions (one on MPH and one on placebo) that included a resting state scan and two inhibitory control tasks; 27 typically developing (TD) children completed the same protocol without medication. Network control theory, which quantifies how brain activity reacts to system inputs based on underlying connectivity, was used to assess differences in average and modal functional controllability during rest and both tasks between TD children and children with ADHD (on and off MPH) and between children with ADHD on and off MPH. Children with ADHD on placebo exhibited higher average controllability and lower modal controllability of attention, reward, and somatomotor networks than TD children. Children with ADHD on MPH were statistically indistinguishable from TD children on almost all controllability metrics. These findings suggest that MPH may stabilize functional network dynamics in children with ADHD, both reducing reactivity of brain organization and making it easier to achieve brain states necessary for cognitively demanding tasks.

Effects of a single-dose methylphenidate challenge on resting-state functional connectivity in stimulant-treatment naive children and adults with ADHD.

Prior studies suggest that methylphenidate, the primary pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), alters functional brain connectivity. As the neurotransmitter systems targeted by methylphenidate undergo significant alterations throughout development, the effects of methylphenidate on functional connectivity may also be modulated by age. Therefore, we assessed the effects of a single methylphenidate challenge on brain network connectivity in stimulant-treatment naïve children and adults with ADHD. We obtained resting-state functional MRI from 50 boys (10-12 years of age) and 49 men (23-40 years of age) with ADHD (DSM IV, all subtypes), before and after an oral challenge with 0.5 mg/kg methylphenidate; and from 11 boys and 12 men as typically developing controls. Connectivity strength (CS), eigenvector centrality (EC), and betweenness centrality (BC) were calculated for the striatum, thalamus, dorsal anterior cingulate cortex (dACC), and prefrontal cortex (PFC). In line with our hypotheses, we found that methylphenidate decreased measures of connectivity and centrality in the striatum and thalamus in children with ADHD, but increased the same metrics in adults with ADHD. Surprisingly, we found no major effects of methylphenidate in the dACC and PFC in either children or adults. Interestingly, pre-methylphenidate, participants with ADHD showed aberrant connectivity and centrality compared to controls predominantly in frontal regions. Our findings demonstrate that methylphenidate's effects on connectivity of subcortical regions are age-dependent in stimulant-treatment naïve participants with ADHD, likely due to ongoing maturation of dopamine and noradrenaline systems. These findings highlight the importance for future studies to take a developmental perspective when studying the effects of methylphenidate treatment.

Altered neural flexibility in children with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood, and is often characterized by altered executive functioning. Executive function has been found to be supported by flexibility in dynamic brain reconfiguration. Thus, we applied multilayer community detection to resting-state fMRI data in 180 children with ADHD and 180 typically developing children (TDC) to identify alterations in dynamic brain reconfiguration in children with ADHD. We specifically evaluated MR derived neural flexibility, which is thought to underlie cognitive flexibility, or the ability to selectively switch between mental processes. Significantly decreased neural flexibility was observed in the ADHD group at both the whole brain (raw p = 0.0005) and sub-network levels (p < 0.05, FDR corrected), particularly for the default mode network, attention-related networks, executive function-related networks, and primary networks. Furthermore, the subjects with ADHD who received medication exhibited significantly increased neural flexibility (p = 0.025, FDR corrected) when compared to subjects with ADHD who were medication naïve, and their neural flexibility was not statistically different from the TDC group (p = 0.74, FDR corrected). Finally, regional neural flexibility was capable of differentiating ADHD from TDC (Accuracy: 77% for tenfold cross-validation, 74.46% for independent test) and of predicting ADHD severity using clinical measures of symptom severity (R2: 0.2794 for tenfold cross-validation, 0.156 for independent test). In conclusion, the present study found that neural flexibility is altered in children with ADHD and demonstrated the potential clinical utility of neural flexibility to identify children with ADHD, as well as to monitor treatment responses and disease severity.

Lower Socioeconomic Position Is Associated with Greater Activity in and Integration within an Allostatic-Interoceptive Brain Network in Response to Affective Stimuli.

Socioeconomic inequities shape physical health and emotional well-being. As such, recent work has examined the neural mechanisms through which socioeconomic position (SEP) may influence health. However, there remain critical gaps in knowledge regarding the relationships between SEP and brain function. These gaps include a lack of research on: (1) the association between SEP and brain functioning in later life, (2) relationships between SEP and functioning of the whole brain beyond specific regions of interest, and (3) how neural responses to positive affective stimuli differ by SEP. The current study addressed these gaps by examining the association between SEP (i.e., education, income) and neural responses to affective stimuli among 122 mid- to late-life adults. During MRI scanning, participants viewed 30 positive, 30 negative, and 30 neutral images; activation and network connectivity analyses explored associations between SEP and neural responses to these affective stimuli. Analyses revealed that those with lower SEP showed greater neural activity to both positive and negative images in regions within the allostatic-interoceptive network, a system of regions implicated in representing and regulating physiological states of the body and the external environment. There were no positive associations between SEP and neural responses to negative or positive images. In addition, graph-theory network analyses showed that individuals with lower SEP demonstrated greater global efficiency within the allostatic-interoceptive network and executive control network, across all task conditions. The findings suggest that lower SEP is associated with enhanced neural sensitivity to affective cues that may be metabolically costly to maintain over time and suggest a mechanism by which SEP might get "under the skull" to influence mental and physical well-being.

The Stressed Brain: Neural Underpinnings of Social Stress Processing in Humans.

As humans, we face a variety of social stressors on a regular basis. Given the established role of social stress in influencing physical and psychological functioning, researchers have focused immense efforts on understanding the psychological and physiological changes induced by exposure to acute social stressors. With the advancement of functional magnetic resonance imaging (fMRI), more recent work has sought to identify the neural correlates of processing acute social stress. In this review, we provide an overview of research on the neural underpinnings of social stress processing to date. Specifically, we summarize research that has examined the neural underpinnings of three types of social stressors commonly studied in the literature: social rejection, social evaluation, and racism-related stress. Within our discussion of each type of social stressor, we describe the methods used to induce stress, the brain regions commonly activated among studies investigating that type of stress, and recommendations for future work. This review of the current literature identifies activity in midline regions in both prefrontal and parietal cortices, as well as lateral prefrontal regions, as being associated with processing social rejection. Activity in the insula, thalamus, and inferior frontal gyrus is often found in studies using social evaluation tasks. Finally, racism-related stress is associated with activity in the ventrolateral prefrontal cortex and rostral anterior cingulate cortex. We conclude by taking a "30,000-foot view" of this area of research to provide suggestions for the future of research on the neuroscience of social stress.

Increased integration between default mode and task-relevant networks in children with ADHD is associated with impaired response control.

Default mode network (DMN) dysfunction is theorized to play a role in attention lapses and task errors in children with attention-deficit/hyperactivity disorder (ADHD). In ADHD, the DMN is hyperconnected to task-relevant networks, and both increased functional connectivity and reduced activation are related to poor task performance. The current study extends existing literature by considering interactions between the DMN and task-relevant networks from a brain network perspective and by assessing how these interactions relate to response control. We characterized both static and time-varying functional brain network organization during the resting state in 43 children with ADHD and 43 age-matched typically developing (TD) children. We then related aspects of network integration to go/no-go performance. We calculated participation coefficient (PC), a measure of a region's inter-network connections, for regions of the DMN, canonical cognitive control networks (fronto-parietal, salience/cingulo-opercular), and motor-related networks (somatomotor, subcortical). Mean PC was higher in children with ADHD as compared to TD children, indicating greater integration across networks. Further, higher and less variable PC was related to greater commission error rate in children with ADHD. Together, these results inform our understanding of the role of the DMN and its interactions with task-relevant networks in response control deficits in ADHD.

The maturation and cognitive relevance of structural brain network organization from early infancy to childhood.

The interactions of brain regions with other regions at the network level likely provide the infrastructure necessary for cognitive processes to develop. Specifically, it has been theorized that in infancy brain networks become more modular, or segregated, to support early cognitive specialization, before integration across networks increases to support the emergence of higher-order cognition. The present study examined the maturation of structural covariance networks (SCNs) derived from longitudinal cortical thickness data collected between infancy and childhood (0-6 years). We assessed modularity as a measure of network segregation and global efficiency as a measure of network integration. At the group level, we observed trajectories of increasing modularity and decreasing global efficiency between early infancy and six years. We further examined subject-based maturational coupling networks (sbMCNs) in a subset of this cohort with cognitive outcome data at 8-10 years, which allowed us to relate the network organization of longitudinal cortical thickness maturation to cognitive outcomes in middle childhood. We found that lower global efficiency of sbMCNs throughout early development (across the first year) related to greater motor learning at 8-10 years. Together, these results provide novel evidence characterizing the maturation of brain network segregation and integration across the first six years of life, and suggest that specific trajectories of brain network maturation contribute to later cognitive outcomes.

Differential contributions of static and time-varying functional connectivity to human behavior.

Measures of human brain functional connectivity acquired during the resting-state track critical aspects of behavior. Recently, fluctuations in resting-state functional connectivity patterns-typically averaged across in traditional analyses-have been considered for their potential neuroscientific relevance. There exists a lack of research on the differences between traditional "static" measures of functional connectivity and newly considered "time-varying" measures as they relate to human behavior. Using functional magnetic resonance imagining (fMRI) data collected at rest, and a battery of behavioral measures collected outside the scanner, we determined the degree to which each modality captures aspects of personality and cognitive ability. Measures of time-varying functional connectivity were derived by fitting a hidden Markov model. To determine behavioral relationships, static and time-varying connectivity measures were submitted separately to canonical correlation analysis. A single relationship between static functional connectivity and behavior existed, defined by measures of personality and stable behavioral features. However, two relationships were found when using time-varying measures. The first relationship was similar to the static case. The second relationship was unique, defined by measures reflecting trialwise behavioral variability. Our findings suggest that time-varying measures of functional connectivity are capable of capturing unique aspects of behavior to which static measures are insensitive.

Detecting Task-Dependent Functional Connectivity in Group Iterative Multiple Model Estimation with Person-Specific Hemodynamic Response Functions.

Introduction: Group iterative multiple model estimation (GIMME) has proven to be a reliable data-driven method to arrive at functional connectivity maps that represent associations between brain regions across time in groups and individuals. However, to date, GIMME has not been able to model time-varying task-related effects. This article introduces HRF-GIMME, an extension of GIMME that enables the modeling of the direct and modulatory effects of a task on functional magnetic resonance imaging data collected by using event-related designs. Critically, hemodynamic response function (HRF)-GIMME incorporates person-specific modeling of the HRF to accommodate known variability in onset delay and shape. Methods: After an introduction of the technical aspects of HRF-GIMME, the performance of HRF-GIMME is evaluated via both a simulation study and application to empirical data. The simulation study assesses the sensitivity and specificity of HRF-GIMME by using data simulated from one slow and two rapid event-related designs, and HRF-GIMME is then applied to two empirical data sets from similar designs to evaluate performance in recovering known neural circuitry. Results: HRF-GIMME showed high sensitivity and specificity across all simulated conditions, and it performed well in the recovery of expected relations between convolved task vectors and brain regions in both simulated and empirical data, particularly for the slow event-related design. Conclusion: Results from simulated and empirical data indicate that HRF-GIMME is a powerful new tool for obtaining directed functional connectivity maps of intrinsic and task-related connections that is able to uncover what is common across the sample as well as crucial individual-level path connections and estimates. Impact statement Group iterative multiple model estimation (GIMME) is a reliable method for creating functional connectivity maps of the connections between brain regions across time, and it is able to detect what is common across the sample and what is shared between subsets of participants, as well as individual-level path estimates. However, historically, GIMME does not model task-related effects. The novel HRF-GIMME algorithm enables the modeling of direct and modulatory task effects through individual-level estimation of the hemodynamic response function (HRF), presenting a powerful new tool for assessing task effects on functional connectivity networks in functional magnetic resonance imaging data.

Children with attention-deficit/hyperactivity disorder spend more time in hyperconnected network states and less time in segregated network states as revealed by dynamic connectivity analysis.

Previous studies in children with attention-deficit/hyperactivity disorder (ADHD) have observed functional brain network disruption on a whole-brain level, as well as on a sub-network level, particularly as related to the default mode network, attention-related networks, and cognitive control-related networks. Given behavioral findings that children with ADHD have more difficulty sustaining attention and more extreme moment-to-moment fluctuations in behavior than typically developing (TD) children, recently developed methods to assess changes in connectivity over shorter time periods (i.e., "dynamic functional connectivity"), may provide unique insight into dysfunctional network organization in ADHD. Thus, we performed a dynamic functional connectivity (FC) analysis on resting state fMRI data from 38 children with ADHD and 79 TD children. We used Hidden semi-Markov models (HSMMs) to estimate six network states, as well as the most probable sequence of states for each participant. We quantified the dwell time, sojourn time, and transition probabilities across states. We found that children with ADHD spent less total time in, and switched more quickly out of, anticorrelated states involving the default mode network and task-relevant networks as compared to TD children. Moreover, children with ADHD spent more time in a hyperconnected state as compared to TD children. These results provide novel evidence that underlying dynamics may drive the differences in static FC patterns that have been observed in ADHD and imply that disrupted FC dynamics may be a mechanism underlying the behavioral symptoms and cognitive deficits commonly observed in children with ADHD.

Resting-state EEG Connectivity in Young Children with ADHD.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing neurodevelopmental disorder. While early childhood is a crucial time for early intervention, it is characterized by instability of ADHD diagnosis. Neural correlates of ADHD have potential to improve diagnostic accuracy; however, minimal research has focused on early childhood. Research indicates that disrupted neural connectivity is associated with ADHD in older children. Here, we explore network connectivity as a potential neural correlate of ADHD diagnosis in early childhood.Method: We collected EEG data in 52 medication-naïve children with ADHD and in 77 typically developing controls (3-7 years). Data was collected with the EGI 128 HydroCel Sensor Net System, but to optimize the ICA, the data was down sampled to the 10-10 system. Connectivity was measured as the synchronization of the time series of each pair of electrodes. Subsequent analyses utilized graph theoretical methods to further characterize network connectivity.Results: Increased global efficiency, which measures the efficiency of information transfer across the entire brain, was associated with increased inattentive symptom severity. Further, this association was robust to controls for age, IQ, SES, and internalizing psychopathology.Conclusions: Overall, our findings indicate that increased global efficiency, which suggests a hyper-connected neural network, is associated with elevated ADHD symptom severity. These findings extend previous work reporting disruption of neural network connectivity in older children with ADHD into early childhood.

Influence of structural and functional brain connectivity on age-related differences in fluid cognition.

We used graph theoretical measures to investigate the hypothesis that structural brain connectivity constrains the influence of functional connectivity on the relation between age and fluid cognition. Across 143 healthy, community-dwelling adults 19-79 years of age, we estimated structural network properties from diffusion-weighted imaging and functional network properties from resting-state functional magnetic resonance imaging. We confirmed previous reports of age-related decline in the strength and efficiency of structural networks, as well as in the connectivity strength within and between structural network modules. Functional networks, in contrast, exhibited age-related decline only in system segregation, a measure of the distinctiveness among network modules. Aging was associated with decline in a composite measure of fluid cognition, particularly tests of executive function. Functional system segregation was a significant mediator of age-related decline in executive function. Structural network properties did not directly influence the age-related decline in functional system segregation. The raw correlational data underlying the graph theoretical measures indicated that structural connectivity exerts a limited constraint on age-related decline in functional connectivity.

The emergence of a functionally flexible brain during early infancy.

Adult brains are functionally flexible, a unique characteristic that is thought to contribute to cognitive flexibility. While tools to assess cognitive flexibility during early infancy are lacking, we aimed to assess the spatiotemporal developmental features of "neural flexibility" during the first 2 y of life. Fifty-two typically developing children 0 to 2 y old were longitudinally imaged up to seven times during natural sleep using resting-state functional MRI. Using a sliding window approach, MR-derived neural flexibility, a quantitative measure of the frequency at which brain regions change their allegiance from one functional module to another during a given time period, was used to evaluate the temporal emergence of neural flexibility during early infancy. Results showed that neural flexibility of whole brain, motor, and high-order brain functional networks/regions increased significantly with age, while visual regions exhibited a temporally stable pattern, suggesting spatially and temporally nonuniform developmental features of neural flexibility. Additionally, the neural flexibility of the primary visual network at 3 mo of age was significantly and negatively associated with cognitive ability evaluated at 5/6 y of age. The "flexible club," comprising brain regions with neural flexibility significantly higher than whole-brain neural flexibility, were consistent with brain regions known to govern cognitive flexibility in adults and exhibited unique characteristics when compared to the functional hub and diverse club regions. Thus, MR-derived neural flexibility has the potential to reveal the underlying neural substrates for developing a cognitively flexible brain during early infancy.

Network organization during probabilistic learning via taste outcomes.

Reinforcement learning guides food decisions, yet how the brain learns from taste in humans is not fully understood. Existing research examines reinforcement learning from taste using passive condition paradigms, but response-dependent instrumental conditioning better reflects natural eating behavior. Here, we examined brain response during a taste-motivated reinforcement learning task and how measures of task-based network structure were related to behavioral outcomes. During a functional MRI scan, 85 participants completed a probabilistic selection task with feedback via sweet taste or bitter taste. Whole brain response and functional network topology measures, including identification of communities and community segregation, were examined during choice, sweet taste, and bitter taste conditions. Relative to the bitter taste, sweet taste was associated with increased whole brain response in the hippocampus, oral somatosensory cortex, and orbitofrontal cortex. Sweet taste was also related to differential community assignment of the ventromedial prefrontal cortex and ventrolateral prefrontal cortex compared to bitter taste. During choice, increasing segregation of a community containing the amygdala, hippocampus, and right fusiform gyrus was associated with increased sensitivity to punishment on the task's posttest. Further, normal BMI was associated with differential community structure compared to overweight and obese BMI, where high BMI reflected increased connectivity of visual regions. Together, results demonstrate that network topology of learning and memory regions during choice is related to avoiding a bitter taste, and that BMI is associated with increased connectivity of area involved in processing external stimuli. Network organization and topology provide unique insight into individual differences in brain response to instrumental conditioning via taste reinforcers.

Bridging global and local topology in whole-brain networks using the network statistic jackknife.

Whole-brain network analysis is commonly used to investigate the topology of the brain using a variety of neuroimaging modalities. This approach is notable for its applicability to a large number of domains, such as understanding how brain network organization relates to cognition and behavior and examining disrupted brain network organization in disease. A benefit to this approach is the ability to summarize overall brain network organization with a single metric (e.g., global efficiency). However, important local differences in network structure might exist without any corresponding observable differences in global topology, making a whole-brain analysis strategy unlikely to detect relevant local findings. Conversely, using local network metrics can identify local differences, but are not directly informative of differences in global topology. Here, we propose the network statistic (NS) jackknife framework, a simulated lesioning method that combines the utility of global network analysis strategies with the ability to detect relevant local differences in network structure. We evaluate the NS jackknife framework with a simulation study and an empirical example comparing global efficiency in children with attention-deficit/hyperactivity disorder (ADHD) and typically developing (TD) children. The NS jackknife framework has been implemented in a public, open-source R package, netjack, available at https://cran.r-project.org/package=netjack.