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The field of neuroscience has largely overlooked the impact of motherhood on brain function outside the context of responses to infant stimuli. Here, we apply spectral dynamic causal modelling (spDCM) to resting-state fMRI data to investigate differences in brain function between a group of 40 first-time mothers at 1-year postpartum and 39 age- and education-matched women who have never been pregnant. Using spDCM, we investigate the directionality (top-down vs. bottom-up) and valence (inhibition vs excitation) of functional connections between six key left hemisphere brain regions implicated in motherhood: the dorsomedial prefrontal cortex, ventromedial prefrontal cortex, posterior cingulate cortex, parahippocampal gyrus, amygdala, and nucleus accumbens. We show a selective modulation of inhibitory pathways related to differences between (1) mothers and non-mothers, (2) the interactions between group and cognitive performance and (3) group and social cognition, and (4) differences related to maternal caregiving behaviour. Across analyses, we show consistent disinhibition between cognitive and affective regions suggesting more efficient, flexible, and responsive behaviour, subserving cognitive performance, social cognition, and maternal caregiving. Together our results support the interpretation of these key regions as constituting a parental caregiving network. The nucleus accumbens and the parahippocampal gyrus emerging as 'hub' regions of this network, highlighting the global importance of the affective limbic network for maternal caregiving, social cognition, and cognitive performance in the postpartum period., (© 2023. Crown.)

Functional positron emission tomography (fPET) imaging using continuous infusion of [18F]-fluorodeoxyglucose (FDG) is a novel neuroimaging technique to track dynamic glucose utilization in the brain. In comparison to conventional static or dynamic bolus PET, fPET maintains a sustained supply of glucose in the blood plasma which improves sensitivity to measure dynamic glucose changes in the brain, and enables mapping of dynamic brain activity in task-based and resting-state fPET studies. However, there is a trade-off between temporal resolution and spatial noise due to the low concentration of FDG and the limited sensitivity of multi-ring PET scanners. Images from fPET studies suffer from partial volume errors and residual scatter noise that may cause the cerebral metabolic functional maps to be biased. Gaussian smoothing filters used to denoise the fPET images are suboptimal, as they introduce additional partial volume errors. In this work, a post-processing framework based on a magnetic resonance (MR) Bowsher-like prior was used to improve the spatial and temporal signal to noise characteristics of the fPET images. The performance of the MR guided method was compared with conventional denosing methods using both simulated and in vivo task fPET datasets. The results demonstrate that the MR-guided fPET framework denoises the fPET images and improves the partial volume correction, consequently enhancing the sensitivity to identify brain activation, and improving the anatomical accuracy for mapping changes of brain metabolism in response to a visual stimulation task. The framework extends the use of functional PET to investigate the dynamics of brain metabolic responses for faster presentation of brain activation tasks, and for applications in low dose PET imaging., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Neuropsychiatric disturbance-particularly executive dysfunction and behavioral dysregulation-is a common feature of Huntington's disease (HD), with implications for functional capacity and quality of life. No study to date has ascertained whether longitudinal change in brain activity is associated with neuropsychiatric deficits in HD. We used a set-response-shifting task together with functional magnetic resonance imaging to investigate 30-month longitudinal blood-oxygen level dependent (BOLD) signal changes in the fronto-striatal attentional control network in premanifest and symptomatic HD (pre-HD and symp-HD, respectively), relative to healthy control participants. We also assessed the extent to which changes in the BOLD signal over time were related to neuropsychiatric measures in the domains of executive dysfunction and behavioral dysregulation. Associations were also evaluated with clinical and disease severity. We found no longitudinal BOLD differences between pre-HD and controls over 30 months. In contrast, reduction in BOLD response over time was greater in symp-HD, relative to controls, in task-related areas (e.g., anterior cingulate cortex and striatum) and in regions from the default mode network (e.g., medial prefrontal cortex and posterior cingulate/precuneus). Moreover, when considered across both premanifest and symptomatic stages, longitudinal BOLD signal decline in the right dorsolateral prefrontal cortex and putamen was associated with executive dysfunction and behavioral dysregulation measures. In addition, longitudinal reduction in BOLD signal, in fronto-striatal and default mode networks, correlated with disease severity. These results suggest that longitudinal change in fronto-striatal and default mode networks may be useful in understanding the biological underpinnings of functional decline in HD. Such findings offer new avenues for targeted treatments in terms of minimizing psychiatric impairment and potentially maximizing cognitive function., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Coughing and the urge-to-cough are important mechanisms that protect the patency of the airways, and are coordinated by the brain. Inhaling a noxious substance leads to a widely distributed network of responses in the brain that are likely to reflect multiple functional processes requisite for perceiving, appraising, and behaviorally responding to airway challenge. The broader brain network responding to airway challenge likely contains subnetworks that are involved in the component functions required for coordinated protective behaviors. Functional connectivity analyses were used to determine whether brain responses to airway challenge could be differentiated regionally during inhalation of the tussive substance capsaicin. Seed regions were defined according to outcomes of previous activation studies that identified regional brain responses consistent with cough suppression, stimulus intensity coding, and perception of urge-to-cough. The subnetworks during continuous inhalation of capsaicin recapitulated the distributed regions previously implicated in discrete functional components of airway challenge. The outcomes of this study highlight the central representation of airways defence as a distributed network., (Copyright © 2014 Wiley Periodicals, Inc.)

Task-evoked changes in cerebral oxygen metabolism can be measured using calibrated functional Magnetic Resonance Imaging (fMRI). This technique requires the use of breathing manipulations such as hypercapnia, hyperoxia or a combination of both to determine a calibration factor M. The M-value is usually obtained by extrapolating the BOLD signal measured during the gas manipulation to its upper theoretical physiological limit using a biophysical model. However, a recently introduced technique uses a combination of increased inspired concentrations of O2 and CO2 to saturate the BOLD signal completely. In this study, we used this BOLD saturation technique to measure M directly at 7Tesla (T). Simultaneous carbogen-7 (7% CO2 in 93% O2) inhalation and visuo-motor task performance were used to elevate venous oxygen saturation in visual and motor areas close to their maximum, and the BOLD signal measured during this manipulation was used as an estimate of M. As accurate estimation of M is crucial for estimation of valid oxidative metabolism values, these directly estimated M-values were assessed and compared with M-values obtained via extrapolation modelling using the generalized calibration model (GCM) on the same dataset. Average M-values measured using both methods were 10.4±3.9% (modelled) and 7.5±2.2% (direct) for a visual-related ROI, and 11.3±5.2% (modelled) and 8.1±2.6% (direct) for a motor-related ROI. Results from this study suggest that, for the CO2 concentration used here, modelling is necessary for the accurate estimation of the M parameter. Neither gas inhalation alone, nor gas inhalation combined with a visuo-motor task, was sufficient to completely saturate venous blood in most subjects. Calibrated fMRI studies should therefore rely on existing models for gas inhalation-based calibration of the BOLD signal., (© 2013 Elsevier Inc. All rights reserved.)

The theoretical basis of linear Gaussian connectivity methods for the analysis of fMRI data is examined in this article, resulting in a clarification of methodological dependencies between techniques. In particular, Granger causality connectivity procedures, which describe instantaneous and directed influence between sets of voxel timeseries, are shown to be remappings of correlation-based metrics. Furthermore, the statistical inference tests applied to pairwise Granger causality measures are theoretically shown to be equivalent to inference tests applied to correlation-based metrics. These results are demonstrated empirically using receiver operating characteristic curves derived from vector autoregressive models of various lags, sample size, and noise covariance values. The equivalence of linear Granger causality and correlation-based methods, in both metric and test statistic, renders linear Granger causality a restatement of traditional data-driven methodologies in the context of brain connectivity studies. Furthermore, the equivalence highlights the centrality of partial correlation and partial variance in linear connectivity analyses and bridges the gap between functional and effective connectivity techniques. Consequently, rather than a distinction rooted in methodological difference, the dichotomy between functional and effective connectivity methods is ultimately a function of model configuration realized in choices such as the selection of nodes, the choice to model instantaneous and/or directed influence, and the choice to employ many bivariate models or a single multivariate model. While these theoretical results may be unsurprising to the reader with advanced statistical knowledge, they highlight the importance of a clear understanding of the theoretical basis of connectivity analysis methods for human brain mapping researchers., (Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.)

While schizophrenia is frequently characterized as a disorder of disturbed functional connectivity, the causes and pathophysiological origins of such disturbances remain unclear. The aim of this study was to better elucidate the mechanistic causes of abnormal functional connectivity in schizophrenia, measured as the extent of temporal correlation between endogenous fluctuations recorded at anatomically discrete brain regions during resting-state functional MRI. An approach was developed to perform whole-brain connectivity mapping at the resolution of individual pairs of voxels, without the need for arbitrary parcellation of the cerebrum. Between-group connectivity reductions in 12 people diagnosed with schizophrenia and 15 age-, IQ-, and gender-matched healthy volunteers were localized to a distributed network including frontoparietal and occipitoparietal connections. The gray-matter regions comprising this disturbed network showed evidence of local reductions in both intra-regional homogeneity (29%-33% reduction) and signal power (40%-60% reduction). The extent to which inter-regional correlation was reduced between a pair of gray matter regions was found to be strongly correlated with the extent of local decoherence evident within the gray matter regions per se. This suggests measurement of aberrant functional connectivity in schizophrenia is both a measurement of altered coupling between regions as well as a measurement of local decoherence within regions., (Copyright © 2011 Wiley Periodicals, Inc.)

The C57BL mouse is the centerpiece of efforts to use gene-targeting technology to understand cerebellar pathology, thus creating a need for a detailed magnetic resonance imaging (MRI) atlas of the cerebellum of this strain. In this study we present a methodology for systematic delineation of the vermal and hemispheric lobules of the C57BL/6J mouse cerebellum in magnetic resonance images. We have successfully delineated 38 cerebellar and cerebellar-related structures. The higher signal-to-noise ratio achieved by group averaging facilitated the identification of anatomical structures. In addition, we have calculated average region volumes and created probabilistic maps for each structure. The segmentation method and the probabilistic maps we have created will provide a foundation for future studies of cerebellar disorders using transgenic mouse models., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The perception of airways irritation is represented in a distributed brain network. However, the functional roles of sub-regions of this network are yet to be determined. The aim of this study was to measure brain activation in healthy participants as they inhaled two doses of capsaicin to identify dose-dependent and dose-independent responses. Blood oxygen level-dependent functional magnetic resonance imaging (fMRI) measures of brain responses during inhalation of saline, and a low and high dose of capsaicin were made from 16 healthy participants. Subjective ratings of the urge-to-cough were also made during capsaicin challenges. The majority of brain regions that were activated during capsaicin inhalation, including insula and mid cingulate cortex, showed graduated responses to the two doses of capsaicin. Prefrontal and parietal regions had dose-independent activation, whereas premotor regions and the cerebellum activated exclusively at the high dose of capsaicin. Activation in the somatosensory and mid-cingulate cortices correlated with ratings of urge-to-cough. In the brainstem, capsaicin produced dose-dependent activations in respiratory-related regions of the dorsal pons and lateral medulla. These data show dissociable response patterns to capsaicin inhalation that may represent different regional processes involved in monitoring and assessing stimulus intensity, determining the spatial localization of the stimulus and suppressing motor responses., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The hippocampal formation plays an important role in cognition, spatial navigation, learning, and memory. High resolution magnetic resonance (MR) imaging makes it possible to study in vivo changes in the hippocampus over time and is useful for comparing hippocampal volume and structure in wild type and mutant mice. Such comparisons demand a reliable way to segment the hippocampal formation. We have developed a method for the systematic segmentation of the hippocampal formation using the perfusion-fixed C57BL/6 mouse brain for application in longitudinal and comparative studies. Our aim was to develop a guide for segmenting over 40 structures in an adult mouse brain using 30 μm isotropic resolution images acquired with a 16.4 T MR imaging system and combined using super-resolution reconstruction., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Excessive coughing is one of the most common reasons for seeking medical advice, yet the available therapies for treating cough disorders are inadequate. Humans can voluntarily cough, choose to suppress their cough, and are acutely aware of an irritation that is present in their airways. This indicates a significant level of behavioral and conscious control over the basic cough reflex pathway. However, very little is known about the neural basis for higher brain regulation of coughing. The aim of the present study was to use functional brain imaging in healthy humans to describe the supramedullary control of cough and cough suppression. Our data show that the brain circuitry activated during coughing in response to capsaicin-evoked airways irritation is not simply a function of voluntarily initiated coughing and the perception of airways irritation. Rather, activations in several brain regions, including the posterior insula and posterior cingulate cortex, define the unique attributes of an evoked cough. Furthermore, the active suppression of irritant-evoked coughing is also associated with a unique pattern of brain activity, including an involvement of the anterior insula, anterior mid-cingulate cortex, and inferior frontal gyrus. These data demonstrate for the first time that evoked cough is not solely a brainstem-mediated reflex response to irritation of the airways, but rather requires active facilitation by cortical regions, and is further regulated by distinct higher order inhibitory processes.

Purpose: The debate regarding how best to model variability of the hemodynamic response function in fMRI data has focussed on the linear vs. nonlinear nature of the optimal signal model, with few studies exploring the deterministic vs. stochastic nature of the dynamics. We propose a stochastic linear model (SLM) of the hemodynamic signal and noise dynamics to more robustly infer fMRI activation estimates., Methods: The SLM models the hemodynamic signal by an exogenous input autoregressive model driven by Gaussian state noise. Activation weights are inferred by a joint state-parameter iterative coordinate descent algorithm based on the Kalman smoother., Results: The SLM produced more accurate parameter estimates than the GLM for event-design simulated data. In application to block-design experimental visuo-motor task fMRI data, the SLM resulted in more punctate and well-defined motor cortex activation maps than the GLM, and was able to track variations in the hemodynamics, as expected from a stochastic model., Conclusions: We demonstrate in application to both simulated and experimental fMRI data that in comparison to the GLM, the SLM produces more flexible, consistent and enhanced fMRI activation estimates.

Mental rotation is a task known to activate the parietal cortical regions. The present study aimed to investigate whether there is differential activation of regions within the parietal lobe and to reveal functional subspecialisation of this region by examining the effects of increasing angle of rotation. Functional magnetic resonance imaging was performed in nine healthy female subjects whilst undertaking a parametric mental rotation task. The task comprised 6 alphanumeric characters presented in their normal or mirror-reversed orientation. Behaviourally, subjects showed increased reaction times with increased angle of rotation, with differential effects between the alphanumeric characters; numbers having greater reaction times than letters. BOLD signal increase was observed bilaterally in the middle occipital gyrus and medial frontal gyrus, in the right superior and inferior parietal lobules and in the left superior temporal gyrus. Parametric increases in activation with increasing angle of rotation were observed bilaterally in the superior and inferior parietal lobules and in the right medial frontal gyrus, with greater parametric effects in the superior parietal lobules compared to the inferior parietal lobules. Our findings suggest subspecialisation of the posterior parietal lobules during mental rotation, with differential responses in the superior and inferior regions., (2009 Elsevier Ltd. All rights reserved.)

Neuroimaging studies of functional activation often only reflect differentiated involvement of brain regions compared between task performance and control states. Signals common for both states are typically not revealed. Previous motor learning studies have shown that extensive motor skill training can induce profound changes in regional activity in both task and control states. To address the issue of brain activity changes in the resting-state, we explored long-term motor training induced neuronal and physiological changes in normal human subjects using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Ten healthy subjects performed a finger movement task daily for four weeks, during which three sessions of fMRI images and two sessions of PET images were acquired. Using a classical data analysis strategy, we found that the brain activation increased first and then returned to the pre-training, replicating previous findings. Interestingly, we also observed that motor skill training induced significant increases in regional cerebral blood flow (rCBF) in both task and resting states as the practice progressed. The apparent decrease in activation may actually result from a greater increase in activity in the resting state, rather than a decrease in the task state. By showing that training can affect the resting state, our findings have profound implications for the interpretation of functional activations in neuroimaging studies. Combining changes in resting state with activation data should greatly enhance our understanding of the mechanisms of motor-skill learning.

FMRI has revealed the presence of correlated low-frequency cerebro-vascular oscillations within functional brain systems, which are thought to reflect an intrinsic feature of large-scale neural activity. The spatial correlations shown by these fluctuations has been their identifying feature, distinguishing them from fluctuations associated with other processes. Major analysis methods characterize these correlations, identifying networks and their interactions with various factors. However, other analysis approaches are required to fully characterize the regional signal dynamics contributing to these correlations between regions. In this study we show that analysis of the power spectral density (PSD) of regional signals can identify changes in oscillatory dynamics across conditions, and is able to characterize the nature and spatial extent of signal changes underlying changes in measures of connectivity. We analyzed spectral density changes in sessions consisting of both resting-state scans and scans recording 2 min blocks of continuous unilateral finger tapping and rest. We assessed the relationship of PSD and connectivity measures by additionally tracking correlations between selected motor regions. Spectral density gradually increased in gray and white matter during the experiment. Finger tapping produced widespread decreases in low-frequency spectral density. This change was symmetric across the cortex, and extended beyond both the lateralized task-related signal increases, and the established "resting-state" motor network. Correlations between motor regions also reduced with task performance. In conclusion, analysis of PSD is a sensitive method for detecting and characterizing BOLD signal oscillations that can enhance the analysis of network connectivity., ((c) 2008 Wiley-Liss, Inc.)

Objective: Previous research has provided conflicting information regarding the pattern of brain activation associated with cognitive performance in depressed people. We aimed to assess brain activation related to cognitive performance during planning and working memory tasks., Method: fMRI scans were conducted using a modified Tower of London task and a 2-back task in 13 patients with major depressive disorder and a matched control group., Results: Task performance was impaired in the depressed group on the Tower of London task but there were no differences between the groups in task performance on the n-back task. The patient group showed widespread increased brain activation in both tasks. There was considerable overlap in increased activation between the two tasks, especially in right prefrontal cortical regions., Conclusions: Patients with depression exhibit increased brain activation, especially in right prefrontal regions, across several types of cognitive task activity. Patients with depression may recruit greater brain regions to achieve similar or even poorer task performance than control subjects., ((c) 2007 Wiley-Liss, Inc.)

Using high-resolution MRI, it is now possible to examine the living human cortex down to a resolution of less than 300 mum. Thus, in vivo imaging is now approaching the resolution that has been successfully used in histological analysis of the cerebral cortex for many years, e.g., low-magnification light microscopy. This allows unprecedented views of cortical microstructure that reflect defined histological features, specifically, individual cortical layers. As in histological brain mapping, it is possible to use the changes in the cortical lamination patterns to define individual cortical areas. This allows in vivo neuroanatomical maps to be generated for individual subjects and precise correlation of the results from functional imaging studies in these subjects with their own microanatomical information. To this end, we adapted the well-established observer-independent cytoarchitectonic mapping techniques for defining cortical borders based on changes in cortical lamination for in vivo parcellation of high-resolution structural MR images.

Objective: To characterize the evolution of brain activation in stroke patients with variable motor recovery and quantify changes relative to healthy controls., Methods: Serial PET activation studies, using a simple finger-tapping task, and quantitative measures of motor performance were obtained in 9 patients (2-7 weeks poststroke and 6 months later) and compared with serial healthy volunteer data., Results: Patients with moderate impairment and good recovery (n = 5) activated the primary sensorimotor cortex (SM1) contralateral to the paretic hand moved, bilateral supplementary motor area (SMA), contralateral cingulate gyrus, and ipsilateral lateral premotor cortex. Activation in the bilateral SMA was greater at the initial study but reduced over time compared to healthy controls and poor recoverers. Patients with severe impairment and poor recovery (n =4) showed limited activation of contralateral SM1 and SMA at both studies and no significant change over time. A posterior shift in SM1 activation was evident in good and poor recoverers., Conclusions: Activation of typical motor regions and recruitment of additional sites occur subacutely poststroke, with evolution to normal patterns in moderately impaired patients who recover well. In comparison, severely impaired, poor-recovery patients show persistent, reduced activation. Dynamic changes in SMA, differentially observed in good recoverers over 6 months, highlight its importance in recovery.

Functional Magnetic Resonance imaging studies analyse sequences of brain volumes whose intensity changes predominantly reflect blood oxygenation level dependent (BOLD) effects. The most comprehensive signal model to date of the BOLD effect is formulated as a continuous-time system of nonlinear stochastic differential equations. In this paper we present a particle filtering method for the analysis of the BOLD system, and demonstrate it to be both accurate and robust in estimating the hidden physiological states including cerebral blood flow, cerebral blood volume, total deoxyhemoglobin content, and the flow inducing signal, from functional imaging data.

Maps of cytoarchitectonically defined cortical areas have proven to be a valuable tool for anatomic localization of activated brain regions revealed by functional imaging studies. However, architectonic data require observations in a sample of postmortem brains. They can only be used reliably for comparison with functional data as probabilistic maps after spatial normalization to a common reference space. The complete architectonic analysis of an individual living brain has not been achievable to date, because the relationship remains unclear between laminar gray value changes of cerebral cortex in magnetic resonance (MR) images and those of cyto- and myeloarchitectonic histologic sections. We examined intensity profiles through the cortex in five imaging modalities: in vivo T1 and postmortem T2 MRI, one cell body stain, and two myelin stains. After visualizing the dissimilarities in the shapes of these profiles using a canonical analysis, differences between the profiles from the different image modalities were compared quantitatively. Subsequently, the profiles extracted from the in vivo T1-weighted images were estimated from profiles extracted from cyto- and myeloarchitectonic sections using linear combinations. We could verify statistically the mixed nature of the cortical T1 signal obtained in vivo: The MR intensity profiles were significantly more similar to myeloarchitectonic than to cytoarchitectonic profiles, but a weighted sum of both fitted the T1 profiles best., (Copyright 2004 Wiley-Liss, Inc.)

Functional magnetic resonance imaging was performed in 16 healthy subjects while they undertook orientation discrimination tasks of real rotating and mentally rotating alphanumeric characters. Perception of rotating and stationary abstract characters was also performed. Mental rotation and the perception of alphanumeric characters undergoing real rotation activated equivalent cortical areas, in keeping with the analogue hypothesis of mental rotation. In addition, areas along the dorsal stream, including the V5/middle temporal complex and the intraparietal sulcus (IPS), were activated during both the real and imaginary rotary conditions. Within the parietal lobe there were areas of convergence (i.e., recruited by all three motion conditions) and areas of divergence (i.e., selectively activated by a particular condition). Tasks requiring canonical-mirror orientation discrimination revealed involvement of neural substrates localized to the ventrolateral bank of the IPS. Tasks in which this judgment was not performed and during which the subject viewed rotary motion of abstract stimuli recruited activity in the medial bank of the IPS. These results indicate subspecialization of the human posterior parietal lobe according to function.

This study used positron-emission tomography to establish the patterns of brain activity involved in the isolated and concurrent experiences of thirst and pain. Ten subjects were scanned while experiencing pain evoked with noxious pressure, while experiencing thirst after the infusion of hypertonic saline, and while experiencing pain when thirsty. After the onset of thirst, noxious pressure evoked more intense sensations of pain. Noxious pressure did not change subjective ratings of thirst. Thirst caused activation in the anterior cingulate (Brodmann area 32) and the insula. Enhanced pain responses were associated with increased activity in cortical regions that are known to correlate with pain intensity, and also with unique activity in the pregenual anterior cingulate and ventral orbitofrontal cortex. These findings suggest a role for limbic and prefrontal cortices in the modulation of pain during the experience of thirst. interoception | neuroimaging

This Special Issue of Human Brain Mapping is dedicated to a 10‐year anniversary of the Enhancing NeuroImaging Genetics through Meta‐Analysis (ENIGMA) Consortium. It reports updates from a broad range of international neuroimaging projects that pool data from around the world to answer fundamental questions in neuroscience. Since ENIGMA was formed in December 2009, the initiative grew into a worldwide effort with over 2,000 participating scientists from 45 countries, and over 50 working groups leading large‐scale studies of human brain disorders. Over the last decade, many lessons were learned on how best to pool brain data from diverse sources. Working groups were created to develop methods to analyze worldwide data from anatomical and diffusion magnetic resonance imaging (MRI), resting state and task‐based functional MRI, electroencephalography (EEG), magnetoencephalography (MEG), and magnetic resonance spectroscopy (MRS). The quest to understand genetic effects on human brain development and disease also led to analyses of brain scans on an unprecedented scale. Genetic roadmaps of the human cortex were created by researchers worldwide who collaborated to perform statistically well‐powered analyses of common and rare genetic variants on brain measures and rates of brain development and aging. Here, we summarize the 31 papers in this Special Issue, covering: (a) technical approaches to harmonize analysis of different types of brain imaging data, (b) reviews of the last decade of work by several of ENIGMA's clinical and technical working groups, and (c) new empirical papers reporting large‐scale international brain mapping analyses in patients with substance use disorders, schizophrenia, bipolar disorders, major depression, posttraumatic stress disorder, obsessive compulsive disorder, epilepsy, and stroke. [ABSTRACT FROM AUTHOR]

Objectives The onset of many illnesses is confounded with age and sex. Increasing age is a risk factor for the development of many illnesses, and sexual dimorphism influences brain anatomy, function, and cognition. Here, we examine frequency-specific connectivity in resting-state networks in a large sample (n = 406) of healthy aged adults. Method We quantify frequency-specific connectivity in three resting-state networks known to be implicated in age-related decline: the default mode, dorsal attention, and salience networks, using multiband functional magnetic resonance imaging. Frequency-specific connectivity was quantified in four bands: low (0.015–0.027 Hz), moderately low (0.027–0.073 Hz), moderately high (0.073–0.198 Hz), and high (0.198–0.5 Hz) frequency bands, using mean intensity and spatial extent. Differences in connectivity between the sexes in each of the three networks were examined. Results Each network showed the largest intensity and spatial extent at low frequencies and smallest extent at high frequencies. Males showed greater connectivity than females in the salience network. Females showed greater connectivity than males in the default mode network. Discussion Results in this healthy aged cohort are compatible with those obtained in young samples, suggesting that frequency-specific connectivity, and differences between the sexes, are maintained into older age. Our results indicate that sex should be considered as an influencing factor in studies of resting-state connectivity. [ABSTRACT FROM AUTHOR]

Abstract: Correlation-based functional MRI connectivity methods typically impose a temporal sample independence assumption on the data. However, the conventional use of temporal filtering to address the high noise content of fMRI data may introduce sample dependence. Violation of the independence assumption has ramifications for the distribution of sample correlation which, if unaccounted for, may invalidate connectivity results. To enable the use of temporal filtering for noise suppression while maintaining the integrity of connectivity results, we derive the distribution of sample correlation between filtered timeseries as a function of the filter frequency response. Corrected distributions are also derived for statistical inference tests of sample correlation between filtered timeseries, including Fisher''s z-transformation and the Student''s t-test. Crucially, the proposed corrections are valid for any unknown true correlation and arbitrary filter specifications. Empirical simulations demonstrate the potential for temporal filtering to artificially induce connectivity by introducing sample dependence, and verify the utility of the proposed corrections in mitigating this effect. The importance of our corrections is exemplified in a resting state fMRI connectivity analysis: seed–voxel correlation maps generated from filtered data using uncorrected test variates yield an unfeasible number of connections to the left primary motor cortex, suggesting artificially induced connectivity, while maps acquired from filtered data using corrected test variates exhibit bilateral connectivity in the primary motor cortex, in conformance with expected results as seen in the literature. [Copyright &y& Elsevier]