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In the search for brain markers of optimal attentional focus, the mainstream approach has been to first define attentional states based on behavioral performance, and to subsequently investigate "neural correlates" associated with these performance variations. However, this approach constrains the range of contexts in which attentional states can be operationalized by relying on overt behavior, and assumes a one-to-one correspondence between behavior and brain state. Here, we reversed the logic of these previous studies and sought to identify behaviorally-relevant brain states based solely on brain activity, agnostic to behavioral performance. In four independent datasets, we found that the same two brain states were dominant during a sustained attention task. One state was behaviorally optimal, with higher accuracy and stability, but a greater tendency to mind wander (State1). The second state was behaviorally suboptimal, with lower accuracy and instability (State2). We further demonstrate how these brain states were impacted by motivation and attention-deficit/hyperactivity disorder (ADHD). Individuals with ADHD spent more time in suboptimal State2 and less time in optimal State1 than healthy controls. Motivation overcame the suboptimal behavior associated with State2. Our study provides compelling evidence for the existence of two attentional states from the sole viewpoint of brain activity., Competing Interests: Conflict of interest statement The authors declare no competing financial interests., (Copyright © 2021. Published by Elsevier Inc.)

A common behavioral marker of optimal attention focus is faster responses or reduced response variability. Our previous study found two dominant brain states during sustained attention, and these states differed in their behavioral accuracy and reaction time (RT) variability. However, RT distributions are often positively skewed with a long tail (i.e., reflecting occasional slow responses). Therefore, a larger RT variance could also be explained by this long tail rather than the variance around an assumed normal distribution (i.e., reflecting pervasive response instability based on both faster and slower responses). Resolving this ambiguity is important for better understanding mechanisms of sustained attention. Here, using a large dataset of over 20,000 participants who performed a sustained attention task, we first demonstrated the utility of the exGuassian distribution that can decompose RTs into a strategy factor, a variance factor, and a long tail factor. We then investigated which factor(s) differed between the two brain states using fMRI. Across two independent datasets, results indicate unambiguously that the variance factor differs between the two dominant brain states. These findings indicate that 'suboptimal' is different from 'slow' at the behavior and neural level, and have implications for theoretically and methodologically guiding future sustained attention research., (© 2021. The Author(s).)

Sustained attention is a fundamental cognitive process that can be decoupled from distinct external events, and instead emerges from ongoing intrinsic large-scale network interdependencies fluctuating over seconds to minutes. Lapses of sustained attention are commonly associated with the subjective experience of mind wandering and task-unrelated thoughts. Little is known about how fluctuations in information processing underpin sustained attention, nor how mind wandering undermines this information processing. To overcome this, we used fMRI to investigate brain activity during subjects' performance (n=29) of a cognitive task that was optimized to detect and isolate continuous fluctuations in both sustained attention (via motor responses) and task-unrelated thought (via subjective reports). We then investigated sustained attention with respect to global attributes of communication throughout the functional architecture, i.e., by the segregation and integration of information processing across large scale-networks. Further, we determined how task-unrelated thoughts related to these global information processing markers of sustained attention. The results show that optimal states of sustained attention favor both enhanced segregation and reduced integration of information processing in several task-related large-scale cortical systems with concurrent reduced segregation and enhanced integration in the auditory and sensorimotor systems. Higher degree of mind wandering was associated with losses of the favored segregation and integration of specific subsystems in our sustained attention model. Taken together, we demonstrate that intrinsic ongoing neural fluctuations are characterized by two converging communication modes throughout the global functional architecture, which give rise to optimal and suboptimal attention states. We discuss how these results might potentially serve as neural markers for clinically abnormal attention. SIGNIFICANCE STATEMENT: Most of our brain activity unfolds in an intrinsic manner, i.e., is unrelated to immediate external stimuli or tasks. Here we use a gradual continuous performance task to map this intrinsic brain activity to both fluctuations of sustained attention and mind wandering. We show that optimal sustained attention is associated with concurrent segregation and integration of information processing within many large-scale brain networks, while task-unrelated thought is related to sub-optimal information processing in specific subsystems of this sustained attention network model. These findings provide a novel information processing framework for investigating the neural basis of sustained attention, by mapping attentional fluctuations to genuinely global features of intra-brain communication., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Neural substrates of "mind wandering" have been widely reported, yet experiments have varied in their contexts and their definitions of this psychological phenomenon, limiting generalizability. We aimed to develop and test the generalizability, specificity, and clinical relevance of a functional brain network-based marker for a well-defined feature of mind wandering-stimulus-independent, task-unrelated thought (SITUT). Combining functional MRI (fMRI) with online experience sampling in healthy adults, we defined a connectome-wide model of inter-regional coupling-dominated by default-frontoparietal control subnetwork interactions-that predicted trial-by-trial SITUT fluctuations within novel individuals. Model predictions generalized in an independent sample of adults with attention-deficit/hyperactivity disorder (ADHD). In three additional resting-state fMRI studies (total n = 1115), including healthy individuals and individuals with ADHD, we demonstrated further prediction of SITUT (at modest effect sizes) defined using multiple trait-level and in-scanner measures. Our findings suggest that SITUT is represented within a common pattern of brain network interactions across time scales and contexts.

A large proportion (range of 44-75%) of women who experience intimate-partner violence (IPV) have been shown to sustain repetitive mild traumatic brain injuries (mTBIs) from their abusers. Further, despite requests for research on TBI-related health outcomes, there are currently only a handful of studies addressing this issue and only one prior imaging study that has investigated the neural correlates of IPV-related TBIs. In response, we examined specific regions of white matter microstructure in 20 women with histories of IPV. Subjects were imaged on a 3-Tesla Siemens Magnetom TrioTim scanner using diffusion magnetic resonance imaging. We investigated the association between a score reflecting number and recency of IPV-related mTBIs and fractional anisotropy (FA) in the posterior and superior corona radiata as well as the posterior thalamic radiation, brain regions shown previously to be involved in mTBI. We also investigated the association between several cognitive measures, namely learning, memory, and cognitive flexibility, and FA in the white matter regions of interest. We report a negative correlation between the brain injury score and FA in regions of the posterior and superior corona radiata. We failed to find an association between our cognitive measures and FA in these regions, but the interpretation of these results remains inconclusive due to possible power issues. Overall, these data build upon the small but growing literature demonstrating potential consequences of mTBIs for women experiencing IPV, and further underscore the urgent need for larger and more comprehensive studies in this area.

Human attention is intrinsically dynamic, with focus continuously shifting between elements of the external world and internal, self-generated thoughts. Communication within and between large-scale brain networks also fluctuates spontaneously from moment to moment. However, the behavioral relevance of dynamic functional connectivity and possible link with attentional state shifts is unknown. We used a unique approach to examine whether brain network dynamics reflect spontaneous fluctuations in moment-to-moment behavioral variability, a sensitive marker of attentional state. Nineteen healthy adults were instructed to tap their finger every 600 ms while undergoing fMRI. This novel, but simple, approach allowed us to isolate moment-to-moment fluctuations in behavioral variability related to attention, independent of common confounds in cognitive tasks (e.g., stimulus changes, response inhibition). Spontaneously increasing tap variance ("out-of-the-zone" attention) was associated with increasing activation in dorsal-attention and salience network regions, whereas decreasing tap variance ("in-the-zone" attention) was marked by increasing activation of default mode network (DMN) regions. Independent of activation, tap variance representing out-of-the-zone attention was also time-locked to connectivity both within DMN and between DMN and salience network regions. These results provide novel mechanistic data on the understudied neural dynamics of everyday, moment-to-moment attentional fluctuations, elucidating the behavioral importance of spontaneous, transient coupling within and between attention-relevant networks., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The brain's default mode network (DMN) is highly active during wakeful rest when people are not overtly engaged with a sensory stimulus or externally oriented task. In multiple contexts, increased spontaneous DMN activity has been associated with self-reported episodes of mind-wandering, or thoughts that are unrelated to the present sensory environment. Mind-wandering characterizes much of waking life and is often associated with error-prone, variable behavior. However, increased spontaneous DMN activity has also been reliably associated with stable, rather than variable, behavior. We aimed to address this seeming contradiction and to test the hypothesis that single measures of attentional states, either based on self-report or on behavior, are alone insufficient to account for DMN activity fluctuations. Thus, we simultaneously measured varying levels of self-reported mind-wandering, behavioral variability, and brain activity with fMRI during a unique continuous performance task optimized for detecting attentional fluctuations. We found that even though mind-wandering co-occurred with increased behavioral variability, highest DMN signal levels were best explained by intense mind-wandering combined with stable behavior simultaneously, compared with considering either single factor alone. These brain-behavior-experience relationships were highly consistent within known DMN subsystems and across DMN subregions. In contrast, such relationships were absent or in the opposite direction for other attention-relevant networks (salience, dorsal attention, and frontoparietal control networks). Our results suggest that the cognitive processes that spontaneous DMN activity specifically reflects are only partially related to mind-wandering and include also attentional state fluctuations that are not captured by self-report., Competing Interests: The authors declare no conflict of interest.

Objective: We assessed the neural correlates of adult ADHD in treatment-naïve participants, an approach necessary for identifying neural substrates unconfounded by medication effects., Method: The sample consisted of 24 medication-naïve adults with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnosed ADHD and 24 healthy controls, comparable on age, sex, handedness, reading achievement, IQ, and psychiatric comorbidity. All participants were assessed with structured diagnostic interviews. Magnetic resonance imaging (MRI)-based regional voxel-based morphometry (r-VBM) was used to assess volumetric differences in a priori defined brain regions of interest., Results: VBM analysis revealed group differences in the hypothesized cortical and subcortical areas; however, only cerebellar volume reductions in ADHD retained significance (p < .05) after corrections for multiple comparisons., Conclusion: These results support the notion that medication-naïve ADHD as expressed in adulthood, manifests subtle brain volume reductions from normal in the cerebellum, and possibly in other syndrome-congruent gray-matter structures. Larger samples are required to confirm these findings., (© The Author(s) 2013.)

Objective: To evaluate the impact of therapeutic oral doses of stimulants on the brains of ADHD subjects as measured by magnetic resonance imaging (MRI)-based neuroimaging studies (morphometric, functional, spectroscopy)., Data Sources: We searched PubMed and ScienceDirect through the end of calendar year 2011 using the keywords (1) psychostimulants or methylphenidate or amphetamine, and (2) neuroimaging or MRI or fMRI, and (3) ADHD or ADD or attention-deficit/hyperactivity disorder or attention deficit hyperactivity disorder., Study Selection: We included only English language articles with new data from case-control or placebo controlled studies that examined attention-deficit/hyperactivity disorder (ADHD) subjects on and off psychostimulants (as well as 5 relevant review articles)., Data Extraction: We combined details of study design and medication effects in each imaging modality., Results: We found 29 published studies that met our criteria. These included 6 structural MRI, 20 functional MRI studies, and 3 spectroscopy studies. Methods varied widely in terms of design, analytic technique, and regions of the brain investigated. Despite heterogeneity in methods, however, results were consistent. With only a few exceptions, the data on the effect of therapeutic oral doses of stimulant medication suggest attenuation of structural and functional alterations found in unmedicated ADHD subjects relative to findings in controls., Conclusions: Despite the inherent limitations and heterogeneity of the extant MRI literature, our review suggests that therapeutic oral doses of stimulants decrease alterations in brain structure and function in subjects with ADHD relative to unmedicated subjects and controls. These medication-associated brain effects parallel, and may underlie, the well-established clinical benefits., (© Copyright 2013 Physicians Postgraduate Press, Inc.)

Background: Gray and white matter volume deficits have been reported in many structural magnetic resonance imaging (MRI) studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural MRI studies of adults with ADHD. This study used voxel based morphometry and applied an a priori region of interest approach based on our previous work, as well as from well-developed neuroanatomical theories of ADHD., Methods: Seventy-four adults with DSM-IV ADHD and 54 healthy control subjects comparable on age, sex, race, handedness, IQ, reading achievement, frequency of learning disabilities, and whole brain volume had an MRI on a 1.5T Siemens scanner. A priori region of interest hypotheses focused on reduced volumes in ADHD in dorsolateral prefrontal cortex, anterior cingulate cortex, caudate, putamen, inferior parietal lobule, and cerebellum. Analyses were carried out by FSL-VBM 1.1., Results: Relative to control subjects, ADHD adults had significantly smaller gray matter volumes in parts of six of these regions at p ≤ .01, whereas parts of the dorsolateral prefrontal cortex and inferior parietal lobule were significantly larger in ADHD at this threshold. However, a number of other regions were smaller and larger in ADHD (especially fronto-orbital cortex) at this threshold. Only the caudate remained significantly smaller at the family-wise error rate., Conclusions: Adults with ADHD have subtle volume reductions in the caudate and possibly other brain regions involved in attention and executive control supporting frontostriatal models of ADHD. Modest group brain volume differences are discussed in the context of the nature of the samples studied and voxel based morphometry methodology., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Timing abilities are critical to the successful management of everyday activities and personal safety, and timing abnormalities have been argued to be fundamental to impulsiveness, a core symptom of attention-deficit/hyperactivity disorder (ADHD). Despite substantial evidence of timing deficits in ADHD youth, only two studies have explicitly examined timing in ADHD adults and only at the suprasecond time scale. Also, the neural substrates of these deficits are largely unknown for both youth and adults with ADHD. The present study examined subsecond sensorimotor timing and its neural substrates in ADHD adults., Methods: Using functional magnetic resonance imaging, we examined paced and unpaced finger tapping in a sample of 20 unmedicated adults with ADHD and 19 control subjects comparable on age, sex, and estimated IQ. The blood oxygenation level-dependent contrast response was used to estimate task-related neural activity., Results: Behavioral data showed no between-group differences in mean tapping rates but greater within-subject variability in tap-to-tap intervals for ADHD adults relative to control subjects. Importantly, ADHD adults had greater clock rather than motor variability, consistent with a central timing locus for the atypical movements. The imaging results demonstrated that, relative to control subjects, ADHD adults showed less activity in a number of regions associated with sensorimotor timing, including prefrontal and precentral gyri, basal ganglia, cerebellum, inferior parietal lobule, superior temporal gyri, and insula., Conclusions: Our findings show that subsecond timing abnormalities in ADHD youth persist into adulthood and suggest that abnormalities in the temporal structure of behavior observed in ADHD adults result from atypical function of corticocerebellar and corticostriatal timing systems., (Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Although attention deficit hyperactivity disorder (ADHD) in adults is associated with significant morbidity and dysfunction and afflicts both sexes, relatively few imaging studies have examined female subjects and none have had sufficient power to adequately examine sex differences. The authors examined sex differences in the neural functioning of adults with ADHD during performance of a verbal working memory task., Method: The participants were 44 adults with ADHD matched on age, sex, and estimated IQ to 49 comparison subjects. Accuracy and reaction time on an N-back task were measured to assess working memory. The blood-oxygen-level-dependent functional MRI response was used as a measure of neural activity., Results: A group-by-sex analysis of variance showed no between-group differences in either reaction time or percent correct for the working memory task. For both sexes combined, the adults with ADHD showed less activity than comparison subjects in prefrontal regions. However, sex-by-group analyses revealed an interaction, such that male ADHD subjects showed significantly less activity in right frontal, temporal, and subcortical regions and left occipital and cerebellar regions relative to male comparison subjects, whereas female ADHD subjects showed no differences from female comparison subjects. Exploratory correlation analyses revealed negative associations between working-memory-related activation and number of hyperactive symptoms for men and number of inattentive symptoms for women., Conclusions: Male but not female adults with ADHD showed significantly altered patterns of neural activity during a verbal working memory task. Men and women showed different associations between neural activity and ADHD symptoms.

Background: Although attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) co-occur frequently and represent a particularly morbid clinical form of both disorders, neuroimaging research addressing this co-morbidity is scarce. Our aim was to evaluate the morphometric magnetic resonance imaging (MRI) underpinnings of the co-morbidity of ADHD with BPD, testing the hypothesis that subjects with this co-morbidity would have neuroanatomical correlates of both disorders., Method: Morphometric MRI findings were compared between 31 adults with ADHD and BPD and with those of 18 with BPD, 26 with ADHD, and 23 healthy controls. The volumes (cm(3)) of our regions of interest (ROIs) were estimated as a function of ADHD status, BPD status, age, sex, and omnibus brain volume using linear regression models., Results: When BPD was associated with a significantly smaller orbital prefrontal cortex and larger right thalamus, this pattern was found in co-morbid subjects with ADHD plus BPD. Likewise, when ADHD was associated with significantly less neocortical gray matter, less overall frontal lobe and superior prefrontal cortex volumes, a smaller right anterior cingulate cortex and less cerebellar gray matter, so did co-morbid ADHD plus BPD subjects., Conclusions: Our results support the hypothesis that ADHD and BPD independently contribute to volumetric alterations of selective and distinct brain structures. In the co-morbid state of ADHD plus BPD, the profile of brain volumetric abnormalities consists of structures that are altered in both disorders individually. Attention to co-morbidity is necessary to help clarify the heterogeneous neuroanatomy of both BPD and ADHD.

Many investigators have hypothesized that attention-deficit/hyperactivity disorder (ADHD) involves structural and functional brain abnormalities in frontal-striatal circuitry. Although our review suggests that there is substantial support for this hypothesis, a growing literature demonstrates widespread abnormalities affecting other cortical regions and the cerebellum. Because there is only one report studying adults with ADHD, this summary is based on children. A key limitation of the literature is that most of the studies until recently have been underpowered, using samples of fewer than 20 subjects per group. Nevertheless, these studies are largely consistent with the most comprehensive and definitive study (Castellanos et al 2002). Moreover, studies differ in the degree to which they address the influence of medications, comorbidities, or gender, and most have not addressed potentially important sources of heterogeneity such as family history of ADHD, subtype, or perinatal complications. Despite these limitations, a relatively consistent picture has emerged. The most replicated alterations in ADHD in childhood include significantly smaller volumes in the dorsolateral prefrontal cortex, caudate, pallidum, corpus callosum, and cerebellum. These results suggest that the brain is altered in a more widespread manner than has been previously hypothesized. Developmental studies are needed to address the evolution of this brain disorder into adulthood.

Cross-sectional data suggest that brain dysfunctions are a central component of attention-deficit/hyperactivity disorder (ADHD) in children, and a growing literature is suggesting the same for adults. This article reviews the current state of the literature pertaining to the structural and functional brain abnormalities that are found in adults with ADHD. Because the literature on ADHD in children is more extensive than that reported heretofore in ADHD in adults,the authors include brief summaries of the child literature to help inform that found in adults.