Age, Motion, Medical, and Psychiatric Associations With Incidental Findings in Brain MRI.

Importance: Few investigations have evaluated rates of brain-based magnetic resonance imaging (MRI) incidental findings (IFs) in large lifespan samples, their stability over time, or their associations with health outcomes. Objectives: To examine rates of brain-based IFs across the lifespan, their persistence, and their associations with phenotypic indicators of behavior, cognition, and health; to compare quantified motion with radiologist-reported motion and evaluate its associations with IF rates; and to explore IF consistency across multiple visits. Design, Setting, and Participants: This cross-sectional study included participants from the Nathan Kline Institute-Rockland Sample (NKI-RS), a lifespan community-ascertained sample, and the Healthy Brain Network (HBN), a cross-sectional community self-referred pediatric sample focused on mental health and learning disorders. The NKI-RS enrolled participants (ages 6-85 years) between March 2012 and March 2020 and had longitudinal participants followed up for as long as 4 years. The HBN enrolled participants (ages 5-21 years) between August 2015 and October 2021. Clinical neuroradiology MRI reports were coded for radiologist-reported motion as well as presence, type, and clinical urgency (category 1, no abnormal findings; 2, no referral recommended; 3, consider referral; and 4, immediate referral) of IFs. MRI reports were coded from June to October 2021. Data were analyzed from November 2021 to February 2023. Main Outcomes and Measures: Rates and type of IFs by demographic characteristics, health phenotyping, and motion artifacts; longitudinal stability of IFs; and Euler number in projecting radiologist-reported motion. Results: A total of 1300 NKI-RS participants (781 [60.1%] female; mean [SD] age, 38.9 [21.8] years) and 2772 HBN participants (976 [35.2%] female; mean [SD] age, 10.0 [3.5] years) had health phenotyping and neuroradiology-reviewed MRI scans. IFs were common, with 284 of 2956 children (9.6%) and 608 of 1107 adults (54.9%) having IFs, but rarely of clinical concern (category 1: NKI-RS, 619 [47.6%]; HBN, 2561 [92.4%]; category 2: NKI-RS, 647 [49.8%]; HBN, 178 [6.4%]; category 3: NKI-RS, 79 [6.1%]; HBN, 30 [1.1%]; category 4: NKI-RS: 12 [0.9%]; HBN, 6 [0.2%]). Overall, 46 children (1.6%) and 79 adults (7.1%) required referral for their IFs. IF frequency increased with age. Elevated blood pressure and BMI were associated with increased T2 hyperintensities and age-related cortical atrophy. Radiologist-reported motion aligned with Euler-quantified motion, but neither were associated with IF rates. Conclusions and Relevance: In this cross-sectional study, IFs were common, particularly with increasing age, although rarely clinically significant. While T2 hyperintensity and age-related cortical atrophy were associated with BMI and blood pressure, IFs were not associated with other behavioral, cognitive, and health phenotyping. Motion may not limit clinical IF detection.

An open-access dataset of naturalistic viewing using simultaneous EEG-fMRI.

In this work, we present a dataset that combines functional magnetic imaging (fMRI) and electroencephalography (EEG) to use as a resource for understanding human brain function in these two imaging modalities. The dataset can also be used for optimizing preprocessing methods for simultaneously collected imaging data. The dataset includes simultaneously collected recordings from 22 individuals (ages: 23-51) across various visual and naturalistic stimuli. In addition, physiological, eye tracking, electrocardiography, and cognitive and behavioral data were collected along with this neuroimaging data. Visual tasks include a flickering checkerboard collected outside and inside the MRI scanner (EEG-only) and simultaneous EEG-fMRI recordings. Simultaneous recordings include rest, the visual paradigm Inscapes, and several short video movies representing naturalistic stimuli. Raw and preprocessed data are openly available to download. We present this dataset as part of an effort to provide open-access data to increase the opportunity for discoveries and understanding of the human brain and evaluate the correlation between electrical brain activity and blood oxygen level-dependent (BOLD) signals.

Omnipresence of the sensorimotor-association axis topography in the human connectome.

Low-dimensional representations are increasingly used to study meaningful organizational principles within the human brain. Most notably, the sensorimotor-association axis consistently explains the most variance in the human connectome as its so-called principal gradient, suggesting that it represents a fundamental organizational principle. While recent work indicates these low dimensional representations are relatively robust, they are limited by modeling only certain aspects of the functional connectivity structure. To date, the majority of studies have restricted these approaches to the strongest connections in the brain, treating weaker or negative connections as noise despite evidence of meaningful structure among them. The present work examines connectivity gradients of the human connectome across a full range of connectivity strengths and explores the implications for outcomes of individual differences, identifying potential dependencies on thresholds and opportunities to improve prediction tasks. Interestingly, the sensorimotor-association axis emerged as the principal gradient of the human connectome across the entire range of connectivity levels. Moreover, the principal gradient of connections at intermediate strengths encoded individual differences, better followed individual-specific anatomical features, and was also more predictive of intelligence. Taken together, our results add to evidence of the sensorimotor-association axis as a fundamental principle of the brain's functional organization, since it is evident even in the connectivity structure of more lenient connectivity thresholds. These more loosely coupled connections further appear to contain valuable and potentially important information that could be used to improve our understanding of individual differences, diagnosis, and the prediction of treatment outcomes.

A longitudinal resource for studying connectome development and its psychiatric associations during childhood.

Most psychiatric disorders are chronic, associated with high levels of disability and distress, and present during pediatric development. Scientific innovation increasingly allows researchers to probe brain-behavior relationships in the developing human. As a result, ambitions to (1) establish normative pediatric brain development trajectories akin to growth curves, (2) characterize reliable metrics for distinguishing illness, and (3) develop clinically useful tools to assist in the diagnosis and management of mental health and learning disorders have gained significant momentum. To this end, the NKI-Rockland Sample initiative was created to probe lifespan development as a large-scale multimodal dataset. The NKI-Rockland Sample Longitudinal Discovery of Brain Development Trajectories substudy (N = 369) is a 24- to 30-month multi-cohort longitudinal pediatric investigation (ages 6.0-17.0 at enrollment) carried out in a community-ascertained sample. Data include psychiatric diagnostic, medical, behavioral, and cognitive phenotyping, as well as multimodal brain imaging (resting fMRI, diffusion MRI, morphometric MRI, arterial spin labeling), genetics, and actigraphy. Herein, we present the rationale, design, and implementation of the Longitudinal Discovery of Brain Development Trajectories protocol.

The real-time fMRI neurofeedback based stratification of Default Network Regulation Neuroimaging data repository.

This data descriptor describes a repository of openly shared data from an experiment to assess inter-individual differences in default mode network (DMN) activity. This repository includes cross-sectional functional magnetic resonance imaging (fMRI) data from the Multi Source Interference Task, to assess DMN deactivation, the Moral Dilemma Task, to assess DMN activation, a resting state fMRI scan, and a DMN neurofeedback paradigm, to assess DMN modulation, along with accompanying behavioral and cognitive measures. We report technical validation from n=125 participants of the final targeted sample of 180 participants. Each session includes acquisition of one whole-brain anatomical scan and whole-brain echo-planar imaging (EPI) scans, acquired during the aforementioned tasks and resting state. The data includes several self-report measures related to perseverative thinking, emotion regulation, and imaginative processes, along with a behavioral measure of rapid visual information processing. Technical validation of the data confirms that the tasks deactivate and activate the DMN as expected. Group level analysis of the neurofeedback data indicates that the participants are able to modulate their DMN with considerable inter-subject variability. Preliminary analysis of behavioral responses and specifically self-reported sleep indicate that as many as 73 participants may need to be excluded from an analysis depending on the hypothesis being tested. The present data are linked to the enhanced Nathan Kline Institute, Rockland Sample and builds on the comprehensive neuroimaging and deep phenotyping available therein. As limited information is presently available about individual differences in the capacity to directly modulate the default mode network, these data provide a unique opportunity to examine DMN modulation ability in relation to numerous phenotypic characteristics.

Concordance among indices of intrinsic brain function: Insights from inter-individual variation and temporal dynamics.

Various resting-state fMRI (R-fMRI) measures have been developed to characterize intrinsic brain activity. While each of these measures has gained a growing presence in the literature, questions remain regarding the common and unique aspects these indices capture. The present work provided a comprehensive examination of inter-individual variation and intra-individual temporal variation for commonly used measures, including fractional amplitude of low frequency fluctuations, regional homogeneity, voxel-mirrored homotopic connectivity, network centrality and global signal correlation. Regardless of whether examining intra-individual or inter-individual variation, we found that these definitionally distinct R-fMRI indices tend to exhibit a relatively high degree of covariation, which doesn't exist in phase randomized surrogate data. As a measure of intrinsic brain function, concordance for R-fMRI indices was negatively correlated with age across individuals (i.e., concordance among functional indices decreased with age). To understand the functional significance of concordance, we noted that higher concordance was generally associated with higher strengths of R-fMRI indices, regardless of whether looking through the lens of inter-individual (i.e., high vs. low concordance participants) or intra-individual (i.e., high vs. low concordance states identified via temporal dynamic analyses) differences. We also noted a linear increase in functional concordance together with the R-fMRI indices through the scan, which may suggest a decrease in arousal. The current study demonstrated an enriched picture regarding the relationship among the R-fMRI indices, as well as provided new insights in examining dynamic states within and between individuals.

Differential profiles in auditory social cognition deficits between adults with autism and schizophrenia spectrum disorders: A preliminary analysis.

Impairment in social cognition, including emotion recognition, has been extensively studied in both Autism Spectrum Disorders (ASD) and Schizophrenia (SZ). However, the relative patterns of deficit between disorders have been studied to a lesser degree. Here, we applied a social cognition battery incorporating both auditory (AER) and visual (VER) emotion recognition measures to a group of 19 high-functioning individuals with ASD relative to 92 individuals with SZ, and 73 healthy control adult participants. We examined group differences and correlates of basic auditory processing and processing speed. Individuals with SZ were impaired in both AER and VER while ASD individuals were impaired in VER only. In contrast to SZ participants, those with ASD showed intact basic auditory function. Our finding of a dissociation between AER and VER deficits in ASD relative to Sz support modality-specific theories of emotion recognition dysfunction. Future studies should focus on visual system-specific contributions to social cognitive impairment in ASD.

An open science resource for establishing reliability and reproducibility in functional connectomics.

Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics. Specifically, CoRR has aggregated 1,629 typical individuals' resting state fMRI (rfMRI) data (5,093 rfMRI scans) from 18 international sites, and is openly sharing them via the International Data-sharing Neuroimaging Initiative (INDI). To allow researchers to generate various estimates of reliability and reproducibility, a variety of data acquisition procedures and experimental designs are included. Similarly, to enable users to assess the impact of commonly encountered artifacts (for example, motion) on characterizations of inter-individual variation, datasets of varying quality are included.

Relationship of trauma symptoms to amygdala-based functional brain changes in adolescents.

In this pilot study, amygdala connectivity related to trauma symptoms was explored using resting-state functional magnetic resonance imaging (R-fMRI) in 23 healthy adolescents ages 13-17 years with no psychiatric diagnoses. Adolescents completed a self-report trauma symptom checklist and a R-fMRI scan. We examined the relationship of trauma symptoms to resting-state functional connectivity of the amygdala. Increasing self-report of trauma symptoms by adolescents was associated with increasing functional connectivity with the right amygdala and a local limbic cluster and decreasing functional connectivity with the amygdala and a long-range frontoparietal cluster to the left amygdala, which can be a hallmark of immaturity. These pilot findings in adolescents provide preliminary evidence that even mild trauma symptoms can be linked to the configuration of brain networks associated with the amygdala.

The NKI-Rockland Sample: A Model for Accelerating the Pace of Discovery Science in Psychiatry.

The National Institute of Mental Health strategic plan for advancing psychiatric neuroscience calls for an acceleration of discovery and the delineation of developmental trajectories for risk and resilience across the lifespan. To attain these objectives, sufficiently powered datasets with broad and deep phenotypic characterization, state-of-the-art neuroimaging, and genetic samples must be generated and made openly available to the scientific community. The enhanced Nathan Kline Institute-Rockland Sample (NKI-RS) is a response to this need. NKI-RS is an ongoing, institutionally centered endeavor aimed at creating a large-scale (N > 1000), deeply phenotyped, community-ascertained, lifespan sample (ages 6-85 years old) with advanced neuroimaging and genetics. These data will be publically shared, openly, and prospectively (i.e., on a weekly basis). Herein, we describe the conceptual basis of the NKI-RS, including study design, sampling considerations, and steps to synchronize phenotypic and neuroimaging assessment. Additionally, we describe our process for sharing the data with the scientific community while protecting participant confidentiality, maintaining an adequate database, and certifying data integrity. The pilot phase of the NKI-RS, including challenges in recruiting, characterizing, imaging, and sharing data, is discussed while also explaining how this experience informed the final design of the enhanced NKI-RS. It is our hope that familiarity with the conceptual underpinnings of the enhanced NKI-RS will facilitate harmonization with future data collection efforts aimed at advancing psychiatric neuroscience and nosology.

Extracting information from functional connectivity maps via function-on-scalar regression.

Functional connectivity of an individual human brain is often studied by acquiring a resting state functional magnetic resonance imaging scan, and mapping the correlation of each voxel's BOLD time series with that of a seed region. As large collections of such maps become available, including multisite data sets, there is an increasing need for ways to distill the information in these maps in a readily visualized form. Here we propose a two-step analytic strategy. First, we construct connectivity-distance profiles, which summarize the connectivity of each voxel in the brain as a function of distance from the seed, a functional relationship that has attracted much recent interest. Next, these profile functions are regressed on predictors of interest, whether categorical (e.g., acquisition site or diagnostic group) or continuous (e.g., age). This procedure can provide insight into the roles of multiple sources of variation, and detect large-scale patterns not easily available from conventional analyses. We illustrate the proposed methods with a resting state data set pooled across four imaging sites.

Age-related differences in the involvement of the prefrontal cortex in attentional control.

We investigated the relative involvement of cortical regions supporting attentional control in older and younger adults during performance on a modified version of the Stroop task. Participants were exposed to two different types of incongruent trials. One of these, an incongruent-ineligible condition, produces conflict at the non-response level, while the second, an incongruent-eligible condition, produces conflict at both non-response and response levels of information processing. Greater attentional control is needed to perform the incongruent-eligible condition compared to other conditions. We examined the cortical recruitment associated with this task in an event-related functional magnetic resonance imaging paradigm in 25 older and 25 younger adults. Our results indicated that while younger adults demonstrated an increase in the activation of cortical regions responsible for maintaining attentional control in response to increased levels of conflict, such sensitivity and flexibility of the cortical regions to increased attentional control demands was absent in older adults. These results suggest a limitation in older adults' capabilities for flexibly recruiting the attentional network in response to increasing attentional demands.

Top-down attentional control in spatially coincident stimuli enhances activity in both task-relevant and task-irrelevant regions of cortex.

Models of selective attention predict that focused attention to spatially contiguous stimuli may result in enhanced activity in areas of cortex specialized for processing task-relevant and task-irrelevant information. We examined this hypothesis by localizing color-sensitive areas (CSA) and word and letter sensitive areas of cortex and then examining modulation of these regions during performance of a modified version of the Stroop task in which target and distractors are spatially coincident. We report that only the incongruent condition with the highest cognitive demand showed increased activity in CSA relative to other conditions, indicating an attentional enhancement in target processing areas. We also found an enhancement of activity in one region sensitive to word/letter processing during the most cognitively demanding incongruent condition indicating greater processing of the distractor dimension. Correlations with performance revealed that top-down modulation during the task was critical for effective filtering of irrelevant information in conflict conditions. These results support predictions made by models of selective attention and suggest an important mechanism of top-down attentional control in spatially contiguous stimuli.

Dedifferentiation in the visual cortex: an fMRI investigation of individual differences in older adults.

Dedifferentiation, or decreased processing specificity, has been suggested to represent a ubiquitous characteristic of cognitive aging. In this study, we examined both age-related differences and intra-group differences in neural specificity in the ventral visual cortex for color, words, faces and places. Our results demonstrated that neural dedifferentiation was not ubiquitous across stimulus categories. Neural dedifferentiation was also relatively stable, across age, in a group of older adults. Older adults with more overall gray matter showed less neural dedifferentiation in the visual cortex. However, regional gray matter volume was not associated with neural dedifferentiation. We illustrate these effects using a discriminability metric, a signal detection theory measure, for neural dedifferentiation that takes into account both magnitude and variance of brain activation. The dedifferentiation measure provides a quantitative means to examine activation patterns and individual difference factors associated with neural dedifferentiation, and to test theories of behavioral dedifferentiation in cognitive aging literature.

Cortical recruitment during selective attention in multiple sclerosis: an fMRI investigation of individual differences.

Recent studies with multiple sclerosis (MS) participants have provided evidence for cortical reorganization. Greater recruitment of task-related areas and additional brain regions are thought to play an adaptive role in the performance of cognitive tasks. In this study, we compared cortical circuitry recruited by MS patients and controls during a selective attention task that requires both focusing attention on task-relevant information and ignoring or inhibiting task-irrelevant information. Despite comparable behavioral performance, MS patients demonstrated increased neural recruitment of task-related areas along with additional activation of the prefrontal cortices. However, this additional activation was associated with poor behavioral performance, thereby providing evidence against compensatory brain reorganization. Future studies specifically investigating the nature of additional activation seen in MS patients in a wider variety of cognitive tasks would provide insight into the specific cognitive decline in MS.

Greater intake of vitamins B6 and B12 spares gray matter in healthy elderly: a voxel-based morphometry study.

Previous studies have reported that high concentrations of homocysteine and lower concentrations of vitamins B6, B12, and folate increase the risk for cognitive decline and pathology in aging populations. In this cross-sectional study, high resolution magnetic resonance imaging (MRI) scans and a 3-day food diary were collected on 32 community-dwelling adults between the ages of 59 and 79. We examined the relation between vitamins B6, B12, and folate intake on cortical volume using an optimized voxel-based morphometry (VBM) method and global gray and white matter volume after correcting for age, sex, body mass index, calorie intake, and education. All participants met or surpassed the recommended daily intake for these vitamins. In the VBM analysis, we found that adults with greater vitamin B6 intake had greater gray matter volume along the medial wall, anterior cingulate cortex, medial parietal cortex, middle temporal gyrus, and superior frontal gyrus, whereas people with greater B12 intake had greater volume in the left and right superior parietal sulcus. These effects were driven by vitamin supplementation and were negated when only examining vitamin intake from diet. Folate had no effect on brain volume. Furthermore, there was no relationship between vitamins B6, B12, or folate intake on global brain volume measures, indicating that VBM methods are more sensitive for detecting localized differences in gray matter volume than global measures. These results are discussed in relation to a growing literature on vitamin intake on age-related neurocognitive deterioration.

The neural correlates of an expanded functional field of view.

The size of the functional field of view (FFOV) predicts driving safety in older adults ( Owsley et al., 1998), and practice-related changes in the FFOV may transfer to driving safety ( Roenker, Cissell, Ball, Wadley, & Edwards, 2003). We used functional magnetic resonance imaging (fMRI) and behavioral measures to examine how practice with the FFOV task changes older adults' attentional function. Behavioral data collected outside of the MRI revealed that participants in the training group showed larger improvements across conditions than did those in the control group. fMRI data revealed training-related changes in activation in a number of brain regions. In the right precentral gyrus and right inferior frontal gyrus, increases in activation between fMRI sessions correlated positively with increases in accuracy between behavioral sessions. Practice with the FFOV task improves older adults' attentional function by increasing their recruitment of regions traditionally associated with orienting visual attention.

Interactive effects of fitness and hormone treatment on brain health in postmenopausal women.

Recent research in rodents suggests that extended and chronic hormone therapy can exacerbate memory impairments and irreversibly damage cells. However, aerobic fitness regimens have been shown to spare brain tissue and cognitive function. In addition, interactions between estrogen treatment and exercise have been reported in rodents. However, whether aerobic fitness and hormone treatments show interactive effects on human brain tissue and cognition has yet to be determined. Here we report two unique and important results: (a) HRT treatment up to 10 years in duration spares gray matter in prefrontal cortex and is associated with better performance on measures of executive function, whereas HRT treatment beyond 10 years in duration increases the degree of prefrontal deterioration and amplifies the decline on measures of executive functioning (b) higher fitness levels augment the effects of shorter durations of hormone treatment and ameliorate the declines associated with prolonged hormone treatment.

Training-induced functional activation changes in dual-task processing: an FMRI study.

Although training-induced changes in brain activity have been previously examined, plasticity associated with executive functions remains understudied. In this study, we examined training-related changes in cortical activity during a dual task requiring executive control. Two functional magnetic resonance imaging (fMRI) sessions, one before training and one after training, were performed on both a control group and a training group. Using a region-of-interest analysis, we examined Time x Group and Time x Group x Condition interactions to isolate training-dependent changes in activation. We found that most regions involved in dual-task processing before training showed reductions in activation after training. Many of the decreases in activation were correlated with improved performance on the task. We also found an area in the dorsolateral prefrontal cortex that showed an increase in activation for the training group for the dual-task condition, which was also correlated with improved performance. These results are discussed in relation to the efficacy of training protocols for modulating attention and executive functions, dual-task processing, and fMRI correlates of plasticity.

Training-induced plasticity in older adults: effects of training on hemispheric asymmetry.

The extent to which cortical plasticity is retained in old age remains an understudied question, despite large social and scientific implications of such a result. Neuroimaging research reports individual differences in age-related activation, thereby educing speculation that some degree of plasticity may remain throughout life. We conducted a randomized longitudinal dual-task training study to investigate if performance improvements (a) change the magnitude or pattern of fMRI activation, thereby suggesting some plasticity retention in old age and (b) result in a reduction in asymmetry and an increase in age differences in fMRI activation as a compensatory model of performance-related activation predicts. Performance improvements were correlated with an increase in hemispheric asymmetry and a reduction in age differences in ventral and dorsal prefrontal activation. These results provide evidence for plasticity in old age and are discussed in relation to an alternative argument for the role of reduced asymmetry in performance improvements.