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A central goal in systems neuroscience is the parcellation of the cerebral cortex into discrete neurobiological "atoms". Resting-state functional magnetic resonance imaging (rs-fMRI) offers the possibility of in vivo human cortical parcellation. Almost all previous parcellations relied on 1 of 2 approaches. The local gradient approach detects abrupt transitions in functional connectivity patterns. These transitions potentially reflect cortical areal boundaries defined by histology or visuotopic fMRI. By contrast, the global similarity approach clusters similar functional connectivity patterns regardless of spatial proximity, resulting in parcels with homogeneous (similar) rs-fMRI signals. Here, we propose a gradient-weighted Markov Random Field (gwMRF) model integrating local gradient and global similarity approaches. Using task-fMRI and rs-fMRI across diverse acquisition protocols, we found gwMRF parcellations to be more homogeneous than 4 previously published parcellations. Furthermore, gwMRF parcellations agreed with the boundaries of certain cortical areas defined using histology and visuotopic fMRI. Some parcels captured subareal (somatotopic and visuotopic) features that likely reflect distinct computational units within known cortical areas. These results suggest that gwMRF parcellations reveal neurobiologically meaningful features of brain organization and are potentially useful for future applications requiring dimensionality reduction of voxel-wise fMRI data. Multiresolution parcellations generated from 1489 participants are publicly available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/brain_parcellation/Schaefer2018_LocalGlobal).

Measurement of correlations between brain regions (functional connectivity) using blood oxygen level dependent (BOLD) fMRI has proven to be a powerful tool for studying the functional organization of the brain. Recently, dynamic functional connectivity has emerged as a major topic in the resting-state BOLD fMRI literature. Here, using simulations and multiple sets of empirical observations, we confirm that imposed task states can alter the correlation structure of BOLD activity. However, we find that observations of "dynamic" BOLD correlations during the resting state are largely explained by sampling variability. Beyond sampling variability, the largest part of observed "dynamics" during rest is attributable to head motion. An additional component of dynamic variability during rest is attributable to fluctuating sleep state. Thus, aside from the preceding explanatory factors, a single correlation structure-as opposed to a sequence of distinct correlation structures-may adequately describe the resting state as measured by BOLD fMRI. These results suggest that resting-state BOLD correlations do not primarily reflect moment-to-moment changes in cognitive content. Rather, resting-state BOLD correlations may predominantly reflect processes concerned with the maintenance of the long-term stability of the brain's functional organization.

Abstract A central goal in systems neuroscience is the parcellation of the cerebral cortex into discrete neurobiological “atoms”. Resting-state functional magnetic resonance imaging (rs-fMRI) offers the possibility of in-vivo human cortical parcellation. Almost all previous parcellations relied on one of two approaches. The local gradient approach detects abrupt transitions in functional connectivity patterns. These transitions potentially reflect cortical areal boundaries defined by histology or visuotopic fMRI. By contrast, the global similarity approach clusters similar functional connectivity patterns regardless of spatial proximity, resulting in parcels with homogeneous (similar) rs-fMRI signals. Here we propose a gradient-weighted Markov Random Field (gwMRF) model integrating local gradient and global similarity approaches. Using task-fMRI and rs-fMRI across diverse acquisition protocols, we found gwMRF parcellations to be more homogeneous than four previously published parcellations. Furthermore, gwMRF parcellations agreed with the boundaries of certain cortical areas defined using histology and visuotopic fMRI. Some parcels captured sub-areal (somatotopic and visuotopic) features that likely reflect distinct computational units within known cortical areas. These results suggest that gwMRF parcellations reveal neurobiologically meaningful features of brain organization and are potentially useful for future applications requiring dimensionality reduction of voxel-wise fMRI data. Multi-resolution parcellations generated from 1489 participants are available ( https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/brain_parcellation/Schaefer2018_LocalGlobal )

Recent functional magnetic resonance imaging-based resting-state functional connectivity analyses of group average data have characterized large-scale systems that represent a high level in the organizational hierarchy of the human brain. These systems are likely to vary spatially across individuals, even after anatomical alignment, but the characteristics of this variance are unknown. Here, we characterized large-scale brain systems across two independent datasets of young adults. In these individuals, we were able to identify brain systems that were similar to those described in the group average, and we observed that individuals had consistent topological arrangement of the system features present in the group average. However, the size of system features varied across individuals in systematic ways, such that expansion of one feature of a given system predicted expansion of other parts of the system. Individual-specific systems also contained unique topological features not present in group average systems; some of these features were consistent across a minority of individuals. These effects were observed even after controlling for data quality and for the accuracy of anatomical registration. The variability characterized here has important implications for cognitive neuroscience investigations, which often assume the functional equivalence of aligned brain regions across individuals.

Control over behavior is enabled by the brain's control networks, which interact with lower-level sensory motor and default networks to regulate their functions. Such interactions are facilitated by specialized "connector hub" regions that interconnect discrete networks. Previous work has treated hubs as a single category of brain regions, although their unitary nature is dubious when examined in individual brains. Here we investigated the nature of hubs by using fMRI to characterize individual-specific hub regions in two independent datasets. We identified three separable sets of connector hubs that integrate information between specific brain networks. These three hub categories occupy different positions within the brain's network structure; they affect networks differently when artificially lesioned, and they are differentially engaged during cognitive and motor task performance. This work suggests a model of brain organization in which different connector hubs integrate control functions and enable top-down control of separate processing streams.

OBJECTIVES: Impaired social, role, and neurocognitive functioning are preillness characteristics of people who later develop psychosis. In people with schizophrenia, neurocognition and negative symptoms are associated with functional impairment. We examined the relative contributions of neurocognition and symptoms to social and role functioning over time in clinically high-risk (CHR) individuals and determined if negative symptoms mediated the influence of cognition on functioning. METHODS: Social, role, and neurocognitive functioning and positive, negative, and disorganized symptoms were assessed in 167 individuals at CHR for psychosis in the North American Prodrome Longitudinal Study Phase 1 (NAPLS-1), of whom 96 were reassessed at 12 months. RESULTS: Regression analyses indicated that negative symptoms accounted for unique variance in social and role functioning at baseline and follow-up. Composite neurocognition accounted for unique, but modest, variance in social and role functioning at baseline and in role functioning at follow-up. Negative symptoms mediated the relationship between composite neurocognition and social and role functioning across time points. In exploratory analyses, individual tests (IQ estimate, Digit Symbol/Coding, verbal memory) selectively accounted for social and role functioning at baseline and follow-up after accounting for symptoms. When negative symptom items with content overlapping with social and role functioning measures were removed, the relationship between neurocognition and social and role functioning was strengthened. CONCLUSION: The modest overlap among neurocognition, negative symptoms, and social and role functioning indicates that these domains make substantially separate contributions to CHR individuals.

INTRODUCTION: Childhood sexual abuse (CSA) has been identified as a potent risk factor for sexual dysfunction. Certain characteristics of the abuse experience, such as repeated abuse, appear to affect the risk of developing sexual dysfunction. Despite the robust findings that CSA can be detrimental to sexual function, there is little consensus on the exact mechanisms that lead to these difficulties. AIM: To summarize the most up-to-date research on the relation between CSA and women's sexual function. METHODS: The published literature examining the prevalence of sexual dysfunction among women with CSA histories, various types of sexual dysfunctions, and mechanisms proposed to explain the relation between CSA and later sexual difficulties was reviewed. MAIN OUTCOME MEASURES: Review of peer-reviewed literature. RESULTS: Women with abuse histories report higher rates of sexual dysfunction compared with their non-abused peers. The sexual concerns most commonly reported by women with abuse histories include problems with sexual desire and sexual arousal. Mechanisms that have been proposed to explain the relation between CSA and sexual dysfunction include cognitive associations with sexuality, sexual self-schemas, sympathetic nervous system activation, body image and esteem, and shame and guilt. CONCLUSION: Women with CSA histories represent a unique population in the sexual health literature. Review of mechanisms proposed to account for the relation between CSA and sexual health suggests that a lack of positive emotions related to sexuality, rather than greater negative emotions, appears to be more relevant to the sexual health of women with CSA histories. Treatment research has indicated that mindfulness-based sex therapy and expressive writing treatments are particularly effective for this group. Further research is needed to clarify the mechanisms that lead to sexual dysfunction for women with abuse histories to provide more targeted treatments for sexual dysfunction among women with abuse histories. Pulverman CS, Kilimnik CD, Meston CM. The Impact of Childhood Sexual Abuse on Women's Sexual Health: A Comprehensive Review. Sex Med Rev 2018;6:188-200.

The network organization of the human brain varies across individuals, changes with development and aging, and differs in disease. Discovering the major dimensions along which this variability is displayed remains a central goal of both neuroscience and clinical medicine. Such efforts can be usefully framed within the context of the brain's modular network organization, which can be assessed quantitatively using computational techniques and extended for the purposes of multi-scale analysis, dimensionality reduction, and biomarker generation. Although the concept of modularity and its utility in describing brain network organization is clear, principled methods for comparing multi-scale communities across individuals and time are surprisingly lacking. Here, we present a method that uses multi-layer networks to simultaneously discover the modular structure of many subjects at once. This method builds upon the well-known multi-layer modularity maximization technique, and provides a viable and principled tool for studying differences in network communities across individuals and within individuals across time. We test this method on two datasets and identify consistent patterns of inter-subject community variability, demonstrating that this variability - which would be undetectable using past approaches - is associated with measures of cognitive performance. In general, the multi-layer, multi-subject framework proposed here represents an advance over current approaches by straighforwardly mapping community assignments across subjects and holds promise for future investigations of inter-subject community variation in clinical populations or as a result of task constraints.

The effects of the antidepressant venlafaxine (VEN-225 mg daily) and transdiagnostic cognitive behavioral treatment (CBT) alone and in combination on alcohol intake in subjects with co-morbid alcohol use disorders (AUDs) and anxiety disorders were compared. Drinking outcomes and anxiety were assessed for 81 subjects treated for 11 weeks with one of 4 conditions: 1) VEN-CBT, 2) VEN-Progressive Muscle Relaxation therapy (PMR), 3) Placebo (PLC)-CBT and 4) a comparison group of PLC-PMR. For subjects who reported taking at least one dose of study medication, the Time×Group interaction was significant for percent days of heavy drinking and drinks consumed per day. For the measure of percent days heavy drinking, the paired comparison of PLC-CBT versus PLC-PMR group indicated that the PLC-CBT group had greater drinking reductions, whereas other groups were not superior to the comparison group. In Week 11, the proportion of subjects in the PLC-CBT group that had a 50% reduction from baseline in percent days heavy drinking was significantly greater than those in the comparison group. Of the 3 "active treatment" groups only the PLC-CBT group had significantly decreased heavy drinking when contrasted to the comparison group. This finding suggests that the transdiagnostic CBT approach of Barlow and colleagues may have value in the management of heavy drinking in individuals with co-morbid alcoholism and anxiety.

CONTEXT: Virtual reality exposure therapy (VRET) is an extension of traditional exposure therapy and has been used to treat a variety of anxiety disorders. VRET utilizes a computer-generated virtual environment to present fear-relevant stimuli. Recent studies have evaluated the use of VRET for treatment of PTSD; however, a systematic evaluation of the methodological quality of these studies has yet to be conducted. OBJECTIVES: This review aims to (a) identify treatment outcome studies examining the use of VRET for the treatment of PTSD and (b) appraise the methodological quality of each study using the 2010 Consolidating Standards of Reporting Trials (CONSORT) Statement and its 2008 extension for nonpharmacologic interventions. METHODS: Two independent assessors conducted a database search (PsycINFO, Medline, CINAHL, Google Scholar) of studies published between January 1990 and June 2013 that reported outcome data comparing VRET with another type of treatment or a control condition. Next, a CONSORT quality appraisal of each study was completed. RESULTS: The search yielded nine unique studies. The CONSORT appraisal revealed that the methodological quality of studies examining VRET as a treatment for PTSD was variable. CONCLUSION: Although preliminary findings suggest some positive results for VRET as a form of exposure treatment for PTSD, additional research using well-specified randomization procedures, assessor blinding, and monitoring of treatment adherence is warranted. Movement toward greater standardization of treatment manuals, virtual environments, and equipment would further facilitate interpretation and consolidation of this literature.

Despite substantial efforts to counter sexual assault and harassment in the military, both remain persistent in the Armed Services. In February 2021, President Biden directed the U.S. Department of Defense to establish a 90-day Independent Review Commission on Sexual Assault in the Military (IRC) to assess the department's efforts and make actionable recommendations. As servicemembers discharge from the military, effects of military sexual trauma (MST) are often seen in the Veterans Health Administration (VA). In response to an IRC inquiry about VA MST research, we organized an overview on prevalence, adverse consequences, and evidence-based treatments targeting the sequelae of MST. Women are significantly more likely to experience MST than their male counterparts. Other groups with low societal and institutional power (e.g., lower rank) are also at increased risk. Although not all MST survivors experience long-term adverse consequences, for many, they can be significant, chronic, and enduring and span mental and physical health outcomes, as well as cumulative impairments in functioning. Adverse consequences of MST come with commonalities shared with sexual trauma in other settings (e.g., interpersonal betrayal, victim-blaming) as well as unique aspects of the military context, where experiences of interpersonal betrayal may be compounded by perceptions of institutional betrayal (e.g., fear of reprisal or ostracism, having to work/live alongside a perpetrator). MST's most common mental health impact is posttraumatic stress disorder, which rarely occurs in isolation, and may coincide with major depression, anxiety, eating disorders, substance use disorders, and increased suicidality. Physical health impacts include greater chronic disease burden (e.g., hypertension), and impaired reproductive health and sexual functioning. Advances in treatment include evidence-based psychotherapies and novel approaches relying on mind-body interventions and peer support. Nonetheless, much work is needed to enhance detection, access, care, and support or even the best interventions will not be effective.

Despite decades of effort to improve quality and safety in health care, this goal feels increasingly elusive. Successful examples of improvement are infrequently replicated. This scoping review synthesizes 76 empirical or conceptual studies (out of 1208 originally screened) addressing learning in quality or safety improvement, that were published in selected health care and management journals between January 2000 and December 2014 to deepen understanding of the role that collective learning plays in quality and safety improvement. We categorize learning activities using a theoretical model that shows how leadership and environmental factors support collective learning processes and practices, and in turn team and organizational improvement outcomes. By focusing on quality and safety improvement, our review elaborates the premise of learning theory that leadership, environment, and processes combine to create conditions that promote learning. Specifically, we found that learning for quality and safety improvement includes experimentation (including deliberate experimentation, improvisation, learning from failures, exploration, and exploitation), internal and external knowledge acquisition, performance monitoring and comparison, and training. Supportive learning environments are characterized by team characteristics like psychological safety, appreciation of differences, openness to new ideas social motivation, and team autonomy; team contextual factors including learning resources like time for reflection, access to knowledge, organizational capabilities; incentives; and organizational culture, strategy, and structure; and external environmental factors including institutional pressures, environmental dynamism and competitiveness and learning collaboratives. Lastly learning in the context of quality and safety improvement requires leadership that reinforces learning through actions and behaviors that affect people, such as coaching and trust building, and through influencing contextual factors, including providing resources, developing culture, and taking strategic actions that support improvement. Our review highlights the importance of leadership in both promoting a supportive learning environment and implementing learning processes.

In the present study, the authors explored gender differences in attitudinal barriers to and facilitators of care for Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans and examined the relationship of those factors with VA mental health service use among female and male veterans with probable mental health conditions. Data were collected as part of a national cross-sectional survey of OEF/OIF veterans; the current sample was limited to participants with a probable diagnosis of posttraumatic stress disorder, depression, or alcohol abuse (N = 278). Although negligible gender differences were observed in attitudes about VA care and perceived fit in the VA setting, men reported slightly more negative beliefs about mental illness and mental health treatment than women. In addition, logistic regressions revealed different associations with VA mental health service use for women and men. For women only, positive perceptions of VA care were associated with increased likelihood of seeking mental health treatment. For men only, perceived similarity to other VA care users and negative beliefs about mental health treatment were associated with increased likelihood of service use, whereas negative beliefs about mental illness were associated with lower likelihood of service use. For both women and men, perceived entitlement to VA care was associated with increased likelihood of service use and negative beliefs about treatment-seeking were associated with a reduced likelihood of seeking mental health care in the past 6 months. Results support the need for tailored outreach to address unique barriers to mental health treatment for female and male OEF/OIF veterans.

Control of goal-directed tasks is putatively carried out via the cinguloopercular (CO) and frontoparietal (FP) systems. However, it remains unclear whether these systems show dissociable moment-to-moment processing during distinct stages of a trial. Here, we characterize dynamics in the CO and FP networks in a meta-analysis of 5 decision-making tasks using fMRI, with a specialized “slow reveal” paradigm which allows us to measure the temporal characteristics of trial responses. We find that activations in left FP, right FP, and CO systems form separate clusters, pointing to distinct roles in decision-making. Left FP shows early “accumulator-like” responses, suggesting a role in pre-decision processing. CO has a late onset and transient response linked to the decision event, suggesting a role in performance reporting. The majority of right FP regions show late onsets with prolonged responses, suggesting a role in post-recognition processing. These findings expand upon past models, arguing that the CO and FP systems relate to distinct stages of processing within a trial. Furthermore, the findings provide evidence for a heterogeneous profile in the FP network, with left and right FP taking on specialized roles. This evidence informs our understanding of how distinct control networks may coordinate moment-to-moment components of complex actions.

BACKGROUND: The influence of psychotherapy on neurocognition in post-traumatic stress disorder (PTSD) has not been examined methodically. This is despite evidence that pre-treatment learning and memory has been associated with treatment success and that executive function theories emphasize weak executive functions (especially inhibition/switching) are associated with PTSD. OBJECTIVES: To determine (1) if higher pre-treatment learning/memory, inhibition/switching, or both predict treatment success; and (2) if treatment success is associated with specific improvement in inhibition/switching and not learning/memory or working memory, another aspect of executive function. METHODS: Pre-treatment neurocognition and neurocognitive changes (inhibition/switching, learning/memory, working memory) were examined in female veterans with PTSD. They were evaluated before and after 16-weeks of group psychotherapy for PTSD that included three counterbalanced modules (cognitive restructuring therapy, exposure therapy, skills training) with fidelity checks for therapist adherence. RESULTS: Only pre-treatment learning/memory predicted better treatment outcome. Treatment success was associated with improvement in inhibition/switching only, even after controlling for mild traumatic brain injury, and changes in depressive symptoms, working memory, and learning/memory. CONCLUSIONS: Our finding that learning/memory predicted treatment success is consistent with previous studies. We extended these studies by showing that the effect was restricted to learning/memory, which is contrary to the executive function theory of PTSD. In contrast, the fact that only inhibition/switching significantly improved with better treatment success is consistent with its potential importance in maintaining PTSD symptoms. Future research should determine whether inhibition/switching abilities are a risk for development and maintenance of PTSD or whether such abilities have a broader reciprocal relationship with PTSD symptom change. (JINS, 2016, 22, 643-651).

OBJECTIVE: Women with histories of childhood sexual abuse (CSA) are at a higher risk for sexual dysfunction, and show a differential response to sex therapy, than women without abuse histories. The factors underlying those differences have yet to be clearly articulated by the literature. This study examined potential mechanisms of action to account for the relationship between CSA and sexual function. METHOD: Participants were 120 adult women recruited from the local community. Women completed a single laboratory session in which they viewed a short erotic film and completed a battery of questionnaires on sexual health. Data were analyzed with structural equation modeling mediation, an approach that enables comparison between groups of women. RESULTS: Sexual shame completely mediated the relationship between history of CSA and sexual function, and explained this relationship better than any of the other candidate mechanisms. CONCLUSIONS: Several differences have been noted between the sexual function of women with and without histories of CSA. Results suggest that differences in sexual shame may contribute to differences in sexual function between these groups. For women with CSA histories treatments that aim to reduce sexual shame may improve sexual function. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

People differ in how quickly they learn information and how long they remember it, yet individual differences in learning abilities within healthy adults have been relatively neglected. In two studies, we examined the relation between learning rate and subsequent retention using a new foreign-language paired-associates task (the learning-efficiency task), which was designed to eliminate ceiling effects that often accompany standardized tests of learning and memory in healthy adults. A key finding was that quicker learners were also more durable learners (i.e., exhibited better retention across a delay), despite studying the material for less time. Additionally, measures of learning and memory from this task were reliable in Study 1 ( N = 281) across 30 hr and Study 2 ( N = 92; follow-up n = 46) across 3 years. We conclude that people vary in how efficiently they learn, and we describe a reliable and valid method for assessing learning efficiency within healthy adults.

Distinguishing individuals from brain connectivity, and studying the genetic influences on that identification across different ages, improves our basic understanding of functional brain network organization. We applied support vector machine classifiers to two datasets of twins (adult, pediatric) and two datasets of repeat-scan individuals (adult, pediatric). Classifiers were trained on resting state functional connectivity magnetic resonance imaging (rs-fcMRI) data and used to predict individuals and co-twin pairs from independent data. The classifiers successfully identified individuals from a previous scan with 100% accuracy, even when scans were separated by months. In twin samples, classifier accuracy decreased as genetic similarity decreased. Our results demonstrate that classification is stable within individuals, similar within families, and contains similar representations of functional connections over a few decades of life. Moreover, the degree to which these patterns of connections predict siblings' data varied by genetic relatedness, suggesting that genetic influences on rs-fcMRI connectivity are established early in life.

Noninvasive brain stimulation (NIBS) is a promising treatment for psychiatric and neurologic conditions, but outcomes are variable across treated individuals. In principle, precise targeting of individual-specific features of functional brain networks could improve the efficacy of NIBS interventions. Network theory predicts that the role of a node in a network can be inferred from its connections; as such, we hypothesized that targeting individual-specific "hub" brain areas with NIBS should impact cognition more than nonhub brain areas. Here, we first demonstrate that the spatial positioning of hubs is variable across individuals but reproducible within individuals upon repeated imaging. We then tested our hypothesis in healthy individuals using a prospective, within-subject, double-blind design. Inhibition of a hub with continuous theta burst stimulation disrupted information processing during working-memory more than inhibition of a nonhub area, despite targets being separated by only a few centimeters on the right middle frontal gyrus of each subject. Based upon these findings, we conclude that individual-specific brain network features are functionally relevant and could leveraged as stimulation sites in future NIBS interventions.

BACKGROUND: Primary care clinics present challenges to implementing evidence-based psychotherapies (EBPs) for depression and anxiety, and frontline providers infrequently adopt these treatments. The current study explored providers' perspectives on fidelity to a manualized brief cognitive behavioral therapy (CBT) as delivered in primary care clinics as part of a pragmatic randomized trial. Data from the primary study demonstrated the clinical effectiveness of the treatment and indicated that providers delivered brief CBT with high fidelity, as evaluated by experts using a standardized rating form. Data presented here explore challenges providers faced during implementation and how they adapted nonessential intervention components to make the protocol "fit" into their clinical practice. METHODS: A multiprofessional group of providers (n = 18) completed a one-time semi-structured interview documenting their experiences using brief CBT in the primary care setting. Data were analyzed via directed content analysis, followed by inductive sorting of interview excerpts to identify key themes agreed upon by consensus. The Dynamic Adaptation Process model provided an overarching framework to allow better understanding and contextualization of emergent themes. RESULTS: Providers described a variety of adaptations to the brief CBT to better enable its implementation. Adaptations were driven by provider skills and abilities (i.e., using flexible content and delivery options to promote treatment engagement), patient-emergent issues (i.e., addressing patients' broader life and clinical concerns), and system-level resources (i.e., maximizing the time available to provide treatment). CONCLUSIONS: The therapeutic relationship, individual patient factors, and system-level factors were critical drivers guiding how providers adapted EBP delivery to improve the "fit" into their clinical practice. Adaptations were generally informed by tensions between the EBP protocol and patient and system needs and were largely not addressed in the EBP protocol itself. Adaptations were generally viewed as acceptable by study fidelity experts and helped to more clearly define delivery procedures to improve future implementation efforts. It is recommended that future EBP implementation efforts examine the concept of fidelity on a continuum rather than dichotomized as adherent/not adherent with focused efforts to understand the context of EBP delivery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01149772.