Rockland Sample Research Articles

Cerebrovascular reactivity increases across development in multiple networks as revealed by a breath-holding task: A longitudinal fMRI study.

Functional magnetic resonance imaging (fMRI) has been widely used to understand the neurodevelopmental changes that occur in cognition and behavior across childhood. The blood-oxygen-level-dependent (BOLD) signal obtained from fMRI is understood to be comprised of both neuronal and vascular information. However, it is unclear whether the vascular response is altered across age in studies investigating development in children. Since the breath-hold (BH) task is commonly used to understand cerebrovascular reactivity (CVR) in fMRI studies, it can be used to account for developmental differences in vascular response. This study examines how the cerebrovascular response changes over age in a longitudinal children's BH data set from the Nathan Kline Institute (NKI) Rockland Sample (aged 6-18 years old at enrollment). A general linear model approach was applied to derive CVR from BH data. To model both the longitudinal and cross-sectional effects of age on BH response, we used mixed-effects modeling with the following terms: linear, quadratic, logarithmic, and quadratic-logarithmic, to find the best-fitting model. We observed increased BH BOLD signals in multiple networks across age, in which linear and logarithmic mixed-effects models provided the best fit with the lowest Akaike information criterion scores. This shows that the cerebrovascular response increases across development in a brain network-specific manner. Therefore, fMRI studies investigating the developmental period should account for cerebrovascular changes that occur with age.

94 Digitized Archimedes Spiral Drawing in the NKI-Rockland Sample

Objective:Digital cognitive assessments (DCAs) provide insight into cognition and behavior that remains inaccessible through standard assessment approaches. However, the availability of DCAs and the requisite toolkits to extract and analyze meaningful features from these datasets are largely constrained to technical specialists or through fee-for-service commercial entities. The NKI- Rockland Sample provides a large- scale lifespan data sample featuring DCAs, and also openly shares its DCA tasks through the open-source MindLogger platform along with pipelines for feature extraction and analyses. Here we present normative performance from a digital version of Archimedes Spiral Drawing.Participants and Methods:NKI-RS2 participants were largely drawn from the existing NKI-RS participant pool (n= 1,500), aged 885. The NKI-RS2 is in year 1 of data collection; here, we report on a subset of participants (n= 9) who performed a digitized version of the Archimedes Spiral Drawing task. This graphomotor task with well-established research and clinical utility in movement disordered populations was adapted for use for off-the-shelf tablet devices. The NKI-RS2 implements these tasks on an Apple iPad Pro2, sampling participant drawing at 120Hz, and featuring pixel- and millisecond- level resolution for all tasks. On the Spiral Drawing and Recall Tests participants traced five Archimedes spirals from the center outward through four windings presented on the iPad. They were then asked to replicate the spiral freehand three times. From these spiral drawings, we extracted time to completion, distance covered, speed/ speed variability, rotational smoothness, number of crossings, mean absolute error, bias, and goodness of fit to the ideal Archimedes spiral.Results:Comparing the tracing and recall conditions, participants showed significantly faster drawing speed (t[8]=5.32, p< .001), more variable drawing speed (t[8]=5.93, p< .001), reduced goodness of fit to the template t[8]=4.99, p< .002, and reduced rotational smoothness (t[8]=7.43, p< .0003) in the recall conditions. Collapsing across conditions, age predicted more variable drawing speed: t[8]= 2.77 p< .019, greater tracing error (t[8] = 2.69, p< .0227), and reduced rotational smoothness (t[8] = 2.67, p< .024). Between conditions, age predicts a greater increase in drawing speed variability (t[8] = 9.76, p< .0006).Conclusions:Using the open source MindLogger platform and off-the-shelf digital tablets, we were able to replicate classic paper and pen neuropsychological tests. By adapting these tasks to DCA, we were able to extract meaningful features that are not otherwise accessible (drawing speed, variability, etc.), or that would require additional hardware solutions (e.g., dwell time). By making these tasks and their processing pipelines available, the NKI-RS2 can facilitate the democratization of DCA and DCA analysis to a broader range of researchers and clinicians.

34 Attention-Deficit/Hyperactivity Disorder, Emotion Regulation, and Executive Functioning Associated with Educational and Occupational Outcomes in Adults

Objective:While attention-deficit/hyperactivity disorder (ADHD) symptoms, including inattention, hyperactivity, and impulsivity, are normally distributed within the population, features of ADHD have been associated with poor functional outcomes across various domains of life, such as academic achievement and occupational status. However, some individuals with even strong ADHD features show normal or above-average success within these functional domains. Executive dysfunction and emotion regulation abilities are associated with educational attainment and occupational status and may therefore explain some of the heterogeneity in functional outcomes in individuals with mild, moderate, and high levels of ADHD symptoms. In this study, we investigated whether emotion regulation strategy use (i.e., emotion suppression or cognitive reappraisal) and executive function abilities moderate the relationship between ADHD symptoms and occupational status and education attainment in adults.Participants and Methods:Data were collected from 109 adults aged 18 - 85 (M = 38.08, SD = 15.54; 70.6% female) from the Nathan Kline Institute Rockland Sample. All participants completed measures of ADHD symptoms (Conners Adult ADHD Rating Scale), emotion regulation strategy use (Emotion Regulation Questionnaire), and executive functioning (composite scores of inhibition, shifting and fluency from the standardized Delis-Kaplan Executive Function System). In this study, executive function abilities and emotion regulation strategy use were tested as potential moderators of the relationship between ADHD symptoms and functional outcomes using hierarchical regression models.Results:Several two- and three-way interactions predicting occupational status and educational attainment were observed. Education attainment was predicted by hyperactivity and reappraisal (ß = -0.26, p = .006); inattention, shifting, and reappraisal (ß = -0.52, p = .029); inattention, shifting, and suppression (ß = -0.40, p = .049); inattention, fluency, and reappraisal (ß = 0.24, p = .038); hyperactivity, fluency, and reappraisal (ß = 0.27, p = .034); and impulsivity, fluency, and reappraisal (ß = 0.44, p = .004). Occupational status was predicted by inattention and reappraisal, (ß = -0.27, p = .032), hyperactivity and reappraisal (ß = -0.26, p = .004); and impulsivity, fluency, and reappraisal (ß = 0.35, p = .031). Fluency was positively associated with educational attainment when controlling for inattention and impulsivity.Conclusions:Consistent with the hypothesis, the association between ADHD symptoms and both occupational status and educational attainment were moderated by the interaction between emotion regulation strategy use, executive function abilities domains. The observed interactions suggest that both occupational status and educational attainment may depend heavily on one’s intrinsic abilities and traits. Contrary to previous literature, we found no evidence that ADHD symptoms, emotional regulation strategies were independently associated with either educational attainment or occupational status, but this should be validated in a sample with greater representation of adults with clinically significant ADHD.

B - 63 Relationship between Executive Functioning and Trauma Symptom Report in Healthy Older Adults.

The study investigated the relationship between trauma symptoms and executive functioning (EF) in healthy older adults, emphasizing the importance of assessing the trauma history of those with subclinical trauma and stressor-related disorders in neuropsychological evaluations. It was hypothesized that age is negatively correlated with trauma symptoms, and trauma symptoms are negatively correlated with EF performance. This cross-sectional investigation included 520 adults ages 50-85 (67.9% Female; Education: 15.95(2.31); 87.9% White, 7.7% Black, 3.3% Asian, 0.6% Native American, 0.6% Other) from the Nathan Kline Institute's Rockland Sample. Trauma was measured by the total raw score of the Trauma Symptom Checklist-40 (TSC-40) and six subscale scores. EF was measured by performance on selected D-KEFS measures. Separate Pearson correlations were used to compare age to trauma scores, and EF performance to trauma scores. The anxiety subscale of TSC-40 showed a significant weak correlation with age, r (518) = -0.138, p = 0.001. Age was not correlated with any other TSC-40 subscales. The TSC-40 sexual abuse (SA) subscale showed a significant weak correlation with Color-Word Inhibition r(518) = -0.096, p = 0.031 and Trail Making-Switching r(518) = -0.106, p = 0.016. The remaining TSC-40 subscales were not correlated with other EF measures. The study demonstrated that the overall severity of trauma symptoms is not associated with age in older adults. Older adults with fewer symptoms associated with SA showed higher EF abilities. Future investigations will assess how gender and socioeconomic status affect the association between trauma and EF in older adults.

Distinct neurocognitive fingerprints reflect differential associations with risky and impulsive behavior in a neurotypical sample

Engagement in risky and impulsive behavior has long been associated with deficits in neurocognition. However, we have a limited understanding of how multiple subfunctions of neurocognition co-occur within individuals and which combinations of neurocognitive subfunctions are most relevant for risky and impulsive behavior. Using the neurotypical Nathan Kline Institute Rockland Sample (N = 673), we applied a Bayesian latent feature learning model—the Indian Buffet Process—to identify nuanced, individual-specific profiles of multiple neurocognitive subfunctions and examine their relationship to risky and impulsive behavior. All features were within a relatively normative range of neurocognition; however, there was subtle variability related to risky and impulsive behaviors. The relatively overall poorer neurocognition feature correlated with greater affective impulsivity and substance use patterns/problems. The poorer episodic memory and emotion feature correlated with greater trait externalizing and sensation-seeking. The poorer attention feature correlated with increased trait externalizing and negative urgency but decreased positive urgency and substance use. Finally, the average or mixed features negatively correlated with various risky and impulsive behaviors. Estimating nuanced patterns of co-occurring neurocognitive functions can inform our understanding of a continuum of risky and impulsive behaviors.

Basal forebrain functional connectivity as a mediator of associations between cardiorespiratory fitness and cognition in healthy older women.

Age-related cholinergic dysfunction within the basal forebrain (BF) is one of the key hallmarks for age-related cognitive decline. Given that higher cardiorespiratory fitness (CRF) induces neuroprotective effects that may differ by sex, we investigated the moderating effects of sex on the associations between CRF, BF cholinergic function, and cognitive function in older adults. 176 older adults (68.5years) were included from the Nathan Kline Institute Rockland Sample. Functional connectivity (rsFC) of the BF subregions including the medial septal nucleus/diagonal band of Broca (MS/DB) and nucleus basalis of Meynert (NBM) were computed from resting-sate functional MRI. Modified Astrand-Ryhming submaximal cycle ergometer protocol was used to estimate CRF. Trail making task and inhibition performance during the color word interference test from the Delis-Kaplan Executive Function System and Rey Auditory Verbal Learning Test were used to examine cognitive function. Linear regression models were used to assess the associations between CRF, BF rsFC, and cognitive performance after controlling for age, sex, and years of education. Subsequently, we measured the associations between the variables in men and women separately to investigate the sex differences. There was an association between higher CRF and greater rsFC between the NBM and right middle frontal gyrus in older men and women. There were significant associations between CRF, NBM rsFC, and trail making task number-letter switching performance only in women. In women, greater NBM rsFC mediated the association between higher CRF and better trail making task number-letter switching performance. These findings provide evidence that greater NBM rsFC, particularly in older women, may be an underlying neural mechanism for the relationship between higher CRF and better executive function.

(039) Social Support Significantly Mediates the Relationship Between Gender Role Nonconformity and Sexual Dysfunction

Abstract Introduction Uncertainty remains about the psychological and sexual implications of gender role nonconformity (GRNC), generally defined as men endorsing or performing femininity, and women endorsing or performing masculinity. Previous studies have demonstrated that variance in gender presentation is associated with negative psychological consequences. Homophobic stigmatization and internalized homophobia partially mediate this association, suggesting it is not the practice of GRNC that causes distress, but internal or external reactions to it. Objective Here, we test the hypothesis that people reporting higher levels of GRNC will have more sexual dysfunction, and that social support will mediate this relationship. Methods We analyzed data from the Nathan Kline Institute Rockland Sample. The sample we selected includes 781 subjects (age= 48.99 ± 17.42, sex= 67% female). All subjects completed the Sex Role Identity Scale (SRIS) and the Trauma Symptom Checklist (TSC-40). GRNC was quantified by SRIS questions-subjective GRNC was assessed using the question “How feminine/masculine do you think you are?”, behavioral GRNC was assessed with “How feminine/masculine do you act or behave?”, and perceived GRNC with “How feminine/masculine do you think you appear and come across to others?” A composite variable was created to assess overall GRNC. Sexual dysfunction was measured with the relevant TSC-40 subscale. Because the distribution of GRNC scores were not normally distributed, we performed a quantile regression analysis using the quantreg and mediation packages in R to understand the mediation effect of social support on the relationship between GRNC and sexual dysfunction, while controlling for sex, age, sexual orientation, and socioeconomic status. Results In the quantile regression model, GRNC significantly predicted sexual dysfunction (β = 0.86, 95%CI [0.52, 1.20]) and social support significantly predicted sexual dysfunction (β = -3.63, 95%CI [-4.30, -2.42]). In the mediation analysis, there was a significant mediation effect of social support on the relationship between GRNC and sexual dysfunction (β = 0.17, 95%CI [0.04, 0.31], p<0.001), controlling for sex, age, sexual orientation, and socioeconomic status. The mediation effect accounted for 16.56% (95%CI [0.05-0.28], p<0.001) of the variance in sexual dysfunction. Conclusions GRNC significantly predicts sexual dysfunction, and social support significantly mediates this relationship, accounting for a substantial percentage of its variance. These results suggest that although GRNC can be associated with negative psychological and sexual consequences, the impacts are significantly mediated by the quality and strength of social relationships. This supports previous literature suggesting that negative reactions to nonconformity, both personal and systemic, may account for decreased well-being in people exhibiting GRNC. Although the findings are limited by the nature of secondary analyses, these results highlight the clinical significance of understanding GRNC to better treat patients with sexual dysfunction and promote healthy sexual functioning for all individuals. Disclosure No

Visualization of latent components assessed in O*Net occupations (VOLCANO): A robust method for standardized conversion of occupational labels to ratio scale format.

Occupations are typically characterized in nominal form, a format that limits options for hypothesis testing and data analysis. We drew upon ratings of knowledge, skills, and abilities for 966 occupations listed in the US Department of Labor's Occupational Classification Network (O*NET) database to create an accessible, standardized multidimensional space in which occupations can be quantitatively localized and compared. Principal component analysis revealed that the occupation space comprises three main dimensions that correspond to (1) the required amount of education and training, (2) the degree to which an occupation falls within a science, technology, engineering, and mathematics (STEM) discipline versus social sciences and humanities, and (3) whether occupations are more mathematically or health related. Additional occupational spaces reflecting cognitive versus labor-oriented categories were created for finer-grained characterization of dimensions within occupational sets defined by higher or lower required educational preparation. Data-driven groupings of related occupations were obtained with hierarchical cluster analysis (HCA). Proof-of-principle was demonstrated with a real-world dataset (470 participants from the Nathan Kline Institute - Rockland Sample; NKI-RS), whereby verbal and non-verbal abilities-as assessed by standardized testing-were related to the STEM versus social sciences and humanities dimension. Visualization of Latent Components Assessed in O*Net Occupations (VOLCANO) is provided to the research community as a freely accessible tool, along with a Shiny app for users to extract quantitative scores along the relevant dimensions. VOLCANO brings much-needed standardization to unwieldy occupational data. Moreover, it can be used to create new occupational spaces customized to specific research domains.

Cross-cohort replicability and generalizability of connectivity-based psychometric prediction patterns

An increasing number of studies have investigated the relationships between inter-individual variability in brain regions’ connectivity and behavioral phenotypes, making use of large population neuroimaging datasets. However, the replicability of brain-behavior associations identified by these approaches remains an open question. In this study, we examined the cross-dataset replicability of brain-behavior association patterns for fluid cognition and openness predictions using a previously developed region-wise approach, as well as using a standard whole-brain approach. Overall, we found moderate similarity in patterns for fluid cognition predictions across cohorts, especially in the Human Connectome Project Young Adult, Human Connectome Project Aging, and Enhanced Nathan Kline Institute Rockland Sample cohorts, but low similarity in patterns for openness predictions. In addition, we assessed the generalizability of prediction models in cross-dataset predictions, by training the model in one dataset and testing in another. Making use of the region-wise prediction approach, we showed that first, a moderate extent of generalizability could be achieved with fluid cognition prediction, and that, second, a set of common brain regions related to fluid cognition across cohorts could be identified. Nevertheless, the moderate replicability and generalizability could only be achieved in specific contexts. Thus, we argue that replicability and generalizability in connectivity-based prediction remain limited and deserve greater attention in future studies.

The interhemispheric auditory white matter tract is associated with impulsivity

The association between auditory processing and impulsivity has been consistently shown. However, the exact mechanism and pathological relations are not clear. The bilateral auditory cortices are interhemispherically connected through the corpus callosum. We hypothesized that this Interhemispheric Auditory white matter Tract (IAT) is associated with impulsivity. We first isolated the IAT and tested the association between IAT’s integrity and impulsivity using diffusion tensor imaging (DTI) data from Nathan Kline Institute – Rockland Sample. Fractional Anisotropy (FA) was used as an index of white matter integrity. Out of 446 individuals, probabilistic tractography of IAT was successful in 390 individuals. FA of the IAT showed positive association with impulsivity scale, measured by UPPS (urgency, premeditation, perseverance, and sensation seeking) Impulsive Behavior Scale total score. Among five UPPS subscales, sensation seeking showed positive association with IAT FA. Our results showed that higher IAT FA is associated with higher impulsivity, especially with higher sensation seeking. It is suggested that stronger interhemispheric auditory integration is associated with greater impulsivity and sensation seeking.

Morphometric similarity deviations in stimulant use disorder point towards abnormal brain ageing

Chronic drug use negatively impacts ageing, resulting in diminished health and quality of life. However, little is known about biomarkers of abnormal ageing in stimulant drug users. Using morphometric similarity network mapping, a novel approach to structural connectomics, we first mapped cross-sectional morphometric similarity trajectories of ageing in the publicly available Rockland Sample (20–80 years of age, n = 665). We then compared morphometric similarity and neuropsychological function between non-treatment-seeking, actively using patients with stimulant use disorder (n = 183, mean age: 35.6 years) and healthy control participants (n = 148, mean age: 36.0 years). The significantly altered mean regional morphometric similarity was found in 43 cortical regions including the inferior and orbital frontal gyri, pre/postcentral gyri and anterior temporal, superior parietal and occipital areas. Deviations from normative morphometric similarity trajectories in patients with stimulant use disorder suggested abnormal brain ageing. Furthermore, deficits in paired associates learning were consistent with neuropathology associated with both ageing and stimulant use disorder. Morphometric similarity mapping provides a promising biomarker for ageing in health and disease and may complement existing neuropsychological markers of age-related cognitive decline. Neuropathological ageing mechanisms in stimulant use disorder warrant further investigation to develop more age-appropriate treatments for older people addicted to stimulant drugs.

Tract-specific statistics based on diffusion-weighted probabilistic tractography

Diffusion-weighted neuroimaging approaches provide rich evidence for estimating the structural integrity of white matter in vivo, but typically do not assess white matter integrity for connections between two specific regions of the brain. Here, we present a method for deriving tract-specific diffusion statistics, based upon predefined regions of interest. Our approach derives a population distribution using probabilistic tractography, based on the Nathan Kline Institute (NKI) Enhanced Rockland sample. We determine the most likely geometry of a path between two regions and express this as a spatial distribution. We then estimate the average orientation of streamlines traversing this path, at discrete distances along its trajectory, and the fraction of diffusion directed along this orientation for each participant. The resulting participant-wise metrics (tract-specific anisotropy; TSA) can then be used for statistical analysis on any comparable population. Based on this method, we report both negative and positive associations between age and TSA for two networks derived from published meta-analytic studies (the “default mode” and “what-where” networks), along with more moderate sex differences and age-by-sex interactions. The proposed method can be applied to any arbitrary set of brain regions, to estimate both the spatial trajectory and DWI-based anisotropy specific to those regions.

Mean arterial pressure, fitness, and executive function in middle age and older adults.

Previous literature suggests that higher fitness is related to better executive function in older adulthood, but the mechanisms underlying this association are poorly understood. While many studies have focused on these associations in older adulthood, recent evidence suggests the importance of cardiorespiratory fitness (CRF) and long-term blood pressure control on cognitive functioning. The purpose of the current study was to examine whether mean arterial pressure (MAP) mediated the association between CRF and executive function in middle age and older adults. Participants were adults (age 40+) without any self-reported psychiatric and neurological disorders or cognitive impairment from the Nathan Kline Institute Rockland Sample (N=224, M age=56). CRF was defined by V̇O2max estimated via a bike test, neuropsychological testing was used to examine executive functioning, and MAP was calculated from systolic and diastolic blood pressure recordings. Mediation models were analyzed controlling for age, sex, and education. Results indicated that higher CRF was associated with better inhibition (B=-0.0048, t=-2.16, p=0.03) and there was a significant indirect effect of greater CRF on better inhibition through lower MAP (B=-0.0011; CI [-0.0026, -0.0002]). There were additional significant indirect effects of greater CRF and better fluency (B=0.0028; CI [.0009, 0.0053]) and planning (B=0.0037; CI [.0014, 0.0074]) through lower MAP. This suggests that MAP may be an underlaying physiological mechanism by which CRF influences executive function in mid- and older adulthood.

Contribution of vascular risk factors to the relationship between ADHD symptoms and cognition in adults and seniors

Symptoms of attention-deficit/hyperactivity disorder (ADHD) in childhood have been found to be predictive of compromised cognitive function, and possibly even dementia, in later adulthood. This study aimed to test vascular risk as a hypothesized moderator or mediator of this association, because individuals with elevated ADHD symptoms frequently have comorbid vascular disease or risk factors which are recognized to contribute to later-life cognitive decline. Data from 1,092 adults aged 18–85 were drawn from the Enhanced Nathan Kline Institute Rockland Sample. Childhood ADHD symptoms (assessed using the Adult ADHD Clinical Diagnostic Scale) were assessed as predictors of cognitive functioning in adulthood (assessed using subtests from the University of Pennsylvania Computerized Neurocognitive Battery, the Delis-Kaplan Executive Functioning System, and the Wechsler Memory Scale). Vascular risk factors (including diabetes, tobacco use, obesity, hypertension, and hypercholesterolemia) were tested as both a moderator and mediator of this relationship. Childhood ADHD symptoms and vascular risk factors were both independently associated with later-life cognition, but vascular risk was not a significant moderator or mediator of relationships between ADHD symptoms and cognition in statistical models. Results from this large community sample suggest that the relationship between ADHD symptoms and cognition is not accounted for by vascular risk. This question should also be investigated in clinical samples.

Age-dependent relationship of cardiorespiratory fitness and white matter integrity

Growing evidence has linked cardiorespiratory fitness (CRF) to more conserved white matter (WM) microstructure. Additional research is needed to determine which WM tracts are most strongly related to CRF and if the neuroprotective effects of CRF are age-dependent. Participants were community-dwelling adults (N = 499; ages 20−85) from the open-access Nathan Kline Institute – Rockland Sample (NKI-RS) with CRF (bike test) and diffusion tensor imaging (DTI) data. Mixed-effect modeling tested the interaction between CRF and age on global (main effect across 9 tracts) and local (individual tract effects) WM microstructure. Among older participants (age ≥ 60), CRF was significantly related to whole-brain (z-score slope = 0.11) and local WM microstructure within several tracts (| z-score slope | range = 0.13 – 0.27). Significant interactions with age indicated that the CRF–WM relationship was weaker (z-score slope ≤ 0.11) and more limited (one WM tract) in younger adults. The findings highlight the importance of aerobic exercise to maintain brain health into senescence. CRF may preferentially preserve a collection of anterior and posterior WM connections related to visuomotor function.

The Temporal Dynamics of Spontaneous Emotional Brain States and Their Implications for Mental Health.

Temporal processes play an important role in elaborating and regulating emotional responding during routine mind wandering. However, it is unknown whether the human brain reliably transitions among multiple emotional states at rest and how psychopathology alters these affect dynamics. Here, we combined pattern classification and stochastic process modeling to investigate the chronometry of spontaneous brain activity indicative of six emotions (anger, contentment, fear, happiness, sadness, and surprise) and a neutral state. We modeled the dynamic emergence of these brain states during resting-state fMRI and validated the results across two population cohorts-the Duke Neurogenetics Study and the Nathan Kline Institute Rockland Sample. Our findings indicate that intrinsic emotional brain dynamics are effectively characterized as a discrete-time Markov process, with affective states organized around a neutral hub. The centrality of this network hub is disrupted in individuals with psychopathology, whose brain state transitions exhibit greater inertia and less frequent resetting from emotional to neutral states. These results yield novel insights into how the brain signals spontaneous emotions and how alterations in their temporal dynamics contribute to compromised mental health.

Automatic parcellation of resting-state cortical dynamics by iterative community detection and similarity measurements.

To investigate the properties of a large-scale brain network, it is a common practice to reduce the dimension of resting state functional magnetic resonance imaging (rs-fMRI) data to tens to hundreds of nodes. This study presents an analytic streamline that incorporates modular analysis and similarity measurements (MOSI) to fulfill functional parcellation (FP) of the cortex. MOSI is carried out by iteratively dividing a module into sub-modules (via the Louvain community detection method) and unifying similar neighboring sub-modules into a new module (adjacent sub-modules with a similarity index <0.05) until the brain modular structures of successive runs become constant. By adjusting the gamma value, a parameter in the Louvain algorithm, MOSI may segment the cortex with different resolutions. rs-fMRI scans of 33 healthy subjects were selected from the dataset of the Rockland sample. MOSI was applied to the rs-fMRI data after standardized pre-processing steps. The results indicate that the parcellated modules by MOSI are more homogeneous in content. After reducing the grouped voxels to representative neural nodes, the network structures were explored. The resultant network components were comparable with previous reports. The validity of MOSI in achieving data reduction has been confirmed. MOSI may provide a novel starting point for further investigation of the network properties of rs-fMRI data. Potential applications of MOSI are discussed.

Brain anatomical covariation patterns linked to binge drinking and age at first full drink

Binge drinking and age at first full drink (AFD) of alcohol prior to 21 years (AFD < 21) have been linked to neuroanatomical differences in cortical and subcortical grey matter (GM) volume, cortical thickness, and surface area. Despite the importance of understanding network-level relationships, structural covariation patterns among these morphological measures have yet to be examined in relation to binge drinking and AFD < 21. Here, we used the Joint and Individual Variance Explained (JIVE) method to characterize structural covariation patterns common across and specific to morphological measures in 293 participants (149 individuals with past-12-month binge drinking and 144 healthy controls) from the Human Connectome Project (HCP). An independent dataset (Nathan Kline Institute Rockland Sample; NKI-RS) was used to examine reproducibility/generalizability. We identified a reproducible joint component dominated by structural covariation between GM volume in the brainstem and thalamus proper, and GM volume and surface area in prefrontal cortical regions. Using linear mixed regression models, we found that participants with AFD < 21 showed lower joint component scores in both the HCP (beta = 0.059, p-value = 0.016; Cohen’s d = 0.441) and NKI-RS (beta = 0.023, p-value = 0.040, Cohen’s d = 0.216) datasets, whereas the individual thickness component associated with binge drinking (p-value = 0.02) and AFD < 21 (p-value < 0.001) in the HCP dataset was not statistically significant in the NKI-RS sample. Our findings were also generalizable to the HCP full sample (n = 880 participants). Taken together, our results show that use of JIVE analysis in high-dimensional, large-scale, psychiatry-related datasets led to discovery of a reproducible cortical and subcortical structural covariation pattern involving brain regions relevant to thalamic-PFC-brainstem neural circuitry which is related to AFD < 21 and suggests a possible extension of existing addiction neurocircuitry in humans.

Automated age- and sex-specific volumetric estimation of regional brain atrophy: workflow and feasibility

ObjectivesAn automated workflow for age- and sex-specific estimation of regional brain volume changes from structural MRI relative to a standard population is presented and evaluated for feasibility.MethodsT1w MRI scans are preprocessed in a standardized way comprising gray matter (GM) segmentation, normalization, modulation, and spatial smoothing. Resulting GM images are then compared to precomputed age- and sex-specific GM templates derived from the population-based Nathan Kline Institute Rockland Sample, and voxel-wise z-maps are compiled. z-maps are color-coded and fused with the subject’s T1w images. The rate of technical success of the proposed workflow was evaluated in 1330 subjects of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Furthermore, medial temporal atrophy (MTA) was assessed using the color-coded maps and with the MTA visual rating scale in these subjects. Sensitivities and specificity of color-coded maps and MTA scale were compared using McNemar’s test.ResultsOne test dataset was excluded due to severe motion artifacts. Out of the remaining 1329 datasets, atrophy map generation was successful in 1323 ADNI subjects (99.5%). Sensitivity for AD diagnosis (71.4 % vs. 53.3%, p < 0.0001 for left; 70.4% vs. 55.3%, p < 0.0001 for right hemisphere) and for MCI (45.4% vs. 17.4, p < 0.0001 for left; 43.5% vs. 14.6%, p < 0.0001 for right hemisphere) based on medial temporal atrophy assessment in color-coded maps was significantly higher than for MTA visual rating scale, while specificity was lower (78.4% vs. 93.8%, p < 0.0001 for left; 79.4% vs. 95.8%, p < 0.0001 for right hemisphere). The workflow is named veganbagel and is published as open-source software with an integrated PACS interface.ConclusionsAutomated brain volume change estimation with the proposed workflow is feasible and technically dependable. It provides high potential for radiologic assessment of brain volume changes and neurodegenerative diseases.Key Points• A workflow combining techniques from voxel-based morphometry and population-based neuroimaging data is feasible and technically highly dependable.• The workflow is provided as open-source software, named veganbagel.• Sensitivity of medial temporal atrophy assessment in atrophy maps from veganbagel exceeds the sensitivity of MTA visual rating scale for the diagnosis of Alzheimer’s disease.

Estimated Prevalence of Nonverbal Learning Disability Among North American Children and Adolescents

Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial processing but not in reading or verbal ability; in addition, problems in math calculation, visual executive functioning, fine-motor skills, and social skills are often present. To our knowledge, there are no population-based estimates of the prevalence of NVLD in community samples. To estimate the prevalence of the NVLD cognitive profile in 3 independent samples of children and adolescents from studies centered around brain imaging in the US and Canada. This cross-sectional study used data from 2 samples recruited from the community and overselected for children with psychiatric disorders (Healthy Brain Network [HBN], January 1, 2015, to December 31, 2019, and Nathan Kline Institute-Rockland Sample [NKI], January 1, 2011, to December 31, 2018) and 1 community-ascertained population sample (Saguenay Youth Study [SYS], January 1, 2003, to December 31, 2012) overselected for active maternal smoking during pregnancy. Prevalence of NVLD. Criteria for NVLD were based on clinical records of deficits in visual-spatial reasoning and impairment in 2 of 4 domains of function (fine-motor skills, math calculation, visual executive functioning, and social skills). Sample weighting procedures adjusted for demographic differences in sample frequencies compared with underlying target populations. Inflation factor weights accounted for overrepresentation of psychiatric disorders (HBN and NKI samples). Across 3 independent samples, the prevalence of NVLD was estimated among 2596 children and adolescents aged 6 to 19 years (mean [SD] age, 12.5 [3.4] years; 1449 male [55.8%]). After sample and inflation weights were applied, the prevalence of NVLD was 2.78% (95% CI, 2.03%-3.52%) in the HBN sample and 3.9% (95% CI, 1.96%-5.78%) in the NKI sample. In the SYS sample, the prevalence of NVLD was 3.10% (95% CI, 1.93%-4.27%) after applying the sample weight. Across samples and estimation strategies, the population prevalence of NVLD was estimated to range from 3% to 4%. When applied to the US population younger than 18 years, 2.2 million to 2.9 million children and adolescents were estimated to have NVLD. The findings suggest that the prevalence of NVLD in children and adolescents may be 3% to 4%. Given that few youths are diagnosed with NVLD and receive treatment, increased awareness, identification of the underlying neurobiological mechanisms, and development and testing interventions for the disorder are needed.