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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.MethodMorphometric 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 (cm3) 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. [ABSTRACT FROM AUTHOR]

This select overview examines the important intersection of adult domestic violence, including intimate partner violence and elder abuse, with brain injury. Despite the high prevalence of domestic violence amongst brain injury patients, there is a notable gap in screening and management training for providers. To provide optimal patient care, brain injury medicine clinicians must screen, recognize, and treat patients who have experienced domestic violence. This select overview highlights barriers to screening, validated screening tools from other medical disciplines, and management considerations for the brain injury clinician. A suggested protocol for domestic violence screening and management, as well as recommended resources for providers and patients, is summarized.

At least one in three women experience intimate partner violence (IPV) in their lifetime. The most commonly sustained IPV-related brain injuries include strangulation-related alterations in consciousness (S-AICs) and traumatic brain injuries (TBIs). Moreover, survivors of IPV-related S-AICs and/or TBIs often demonstrate psychological distress such as depression, anxiety, and post-traumatic stress. However, the co-occurrence of S-AICs and TBIs, and whether such TBIs may be moderate to severe, has not been systematically examined, and most data have been collected from women in North America. The purpose of this study was to examine the co-occurrence of IPV-related S-AICs and TBIs across a range of geographical locations and to determine the extent to which these S-AICs are related to psychological distress. Women who had experienced physical IPV ( n = 213) were included in this secondary analysis of retrospectively collected data across four countries (Canada, the United States, Spain, and Colombia). The Brain Injury Severity Assessment (BISA) was used to assess IPV-related BI across all sites. Because various questionnaires were employed to assess levels of depression, anxiety, and post-traumatic stress disorder at each site, we created a standardized composite score by converting raw scores into Z -scores for analysis. Mann-Whitney U tests and chi-square tests were conducted to examine differences between women with and without experience of S-AICs and to discover if there was a relationship between the occurrence of S-AICs and TBIs. Analysis of variance and analysis of covariance (to control for the potential confounding effects of age, education, and non IPV-related TBI) were used to compare levels of psychological distress in women who had or had not experienced S-AICs. Approximately, 67% of women sustained at least one IPV-related BI (i.e., TBI and/or S-AIC). In a subsample of women who sustained at least one IPV-related BI, approximately 37% sustained both S-AICs and TBIs, 2% sustained only S-AICs (with no TBIs), and 61% sustained TBIs exclusively (with no S-AICs). Furthermore, women who had sustained S-AICs (with or without a TBI) were more likely to have experienced a moderate-to-severe BI than those who had not sustained an S-AIC (BISA severity subscale: U = 3939, p = 0.006). In addition, women who experienced S-AICs (with or without a TBI) reported higher levels of psychological distress compared with women who never experienced S-AICs, irrespective of whether they occurred once or multiple times. These data underscore the importance of assessing for S-AIC in women who have experienced IPV and when present, to also assess for TBIs and the presence of psychological distress. Unfortunately, there were methodological differences across sites precluding cross-site comparisons. Nonetheless, data were collected across four culturally and geographically diverse countries and, therefore, highlight IPV-related BIs as a global issue that needs to be aggressively studied with policies established and then implemented to address findings.

Intimate partner violence (IPV) is a chronic, traumatic stressor related to posttraumatic stress (PTS), depression, and anxiety. As psychological symptoms are exacerbated in those with poor emotional clarity, the present study evaluates the relationship between emotional clarity and PTS, dissociation, depression, and worry in women who experienced at least one instance of physical IPV ( n  = 88). Hierarchical regression analyses, controlling for childhood trauma, IPV abuse severity, and IPV-related brain injury, found that lack of emotional clarity was significantly related to greater PTS, dissociative experiences, depression, and worry. Results suggest that emotional clarity may be a relevant therapeutic target for individuals with a history of IPV and psychological distress., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Intimate partner violence (IPV) is a significant, global public health concern. Women, individuals with historically underrepresented identities, and disabilities are at high risk for IPV and tend to experience severe injuries. There has been growing concern about the risk of exposure to IPV-related head trauma, resulting in IPV-related brain injury (IPV-BI), and its health consequences. Past work suggests that a significant proportion of women exposed to IPV experience IPV-BI, likely representing a distinct phenotype compared with BI of other etiologies. An IPV-BI often co-occurs with psychological trauma and mental health complaints, leading to unique issues related to identifying, prognosticating, and managing IPV-BI outcomes. The goal of this review is to identify important gaps in research and clinical practice in IPV-BI and suggest potential solutions to address them. We summarize IPV research in five key priority areas: (1) unique considerations for IPV-BI study design; (2) understanding non-fatal strangulation as a form of BI; (3) identifying objective biomarkers of IPV-BI; (4) consideration of the chronicity, cumulative and late effects of IPV-BI; and (5) BI as a risk factor for IPV engagement. Our review concludes with a call to action to help investigators develop ecologically valid research studies addressing the identified clinical-research knowledge gaps and strategies to improve care in individuals exposed to IPV-BI. By reducing the current gaps and answering these calls to action, we will approach IPV-BI in a trauma-informed manner, ultimately improving outcomes and quality of life for those impacted by IPV-BI.

Childhood psychiatric symptoms are often diffuse but can coalesce into discrete mental illnesses during late adolescence. We leveraged polygenic scores (PGSs) to parse genomic risk for childhood symptoms and to uncover related neurodevelopmental mechanisms with transcriptomic and neuroimaging data. In independent samples (Adolescent Brain Cognitive Development, Generation R) a narrow cross-disorder neurodevelopmental PGS, reflecting risk for attention deficit hyperactivity disorder, autism, depression and Tourette syndrome, predicted psychiatric symptoms through early adolescence with greater sensitivity than broad cross-disorder PGSs reflecting shared risk across eight psychiatric disorders, the disorder-specific PGS individually or two other narrow cross-disorder (Compulsive, Mood-Psychotic) scores. Neurodevelopmental PGS-associated genes were preferentially expressed in the cerebellum, where their expression peaked prenatally. Further, lower gray matter volumes in cerebellum and functionally coupled cortical regions associated with psychiatric symptoms in mid-childhood. These findings demonstrate that the genetic underpinnings of pediatric psychiatric symptoms differ from those of adult illness, and implicate fetal cerebellar developmental processes that endure through childhood., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: The aim of this study was to assess the prevalence of brain injury (BI) and its relationship to cognitive and psychological outcomes in women survivors of intimate partner violence (IPV) in Colombia, South America., Setting: Women's shelters and organizations in Barranquilla, Colombia., Participants: Seventy women from the city of Barranquilla, Colombia, who experienced any form of IPV., Design: Cross-sectional, retrospective., Main Measures: Participants were administered the computerized EMBRACED neuropsychological battery to assess learning, working and long-term memory, cognitive flexibility, and processing speed. Participants also completed measures of psychological symptoms. Partner violence severity was assessed with a semistructured interview for survivors of domestic violence. Presence and severity of IPV-related BI were assessed using the Brain Injury Severity Assessment (BISA)., Results: Thirty-one percent of women sustained at least one BI during an abusive relationship, and 10% sustained repetitive BIs. Furthermore, BI was negatively associated with measures of long-term and working memory, cognitive flexibility, as well as a trending ( P = .05) positive association with depression. With the exception of the relationship between BI and cognitive flexibility, which was substantially reduced and no longer significant, all of these relationships were nearly identical in strength when controlling for abuse severity, socioeconomic status, and educational level., Conclusion: These data are the first to specifically examine IPV-related BI in relation to cognitive and psychological functioning in a sample of Colombian women. These data add cross-cultural knowledge to the limited work in this area that has largely focused on women in North America., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Objective: The aim of this work was to examine the relationship between strangulation-related alterations in consciousness (AIC) and cognitive and psychological outcomes in women who have experienced intimate partner violence (IPV)., Setting: Participants were recruited from a variety of settings, including women's shelters and support programs., Participants: A total of 99 women were enrolled in the study. After applying exclusion criteria for factors that could mask or confound the effects of strangulation, 52 women remained for analyses., Design: Cross-sectional, retrospective., Main Measures: We used several cognitive measures to assess learning, long-term and working memory, visuomotor speed, cognitive flexibility, and nonverbal cognitive fluency as well as several psychological measures to assess posttraumatic stress symptomatology, general distress, worry, anhedonic depression, and anxious arousal. We also used the Brain Injury Severity Assessment interview to examine the association between strangulation-related AICs and these measures of cognitive and psychological functioning., Results: Women who had experienced strangulation-related AICs performed more poorly on a test of long-term memory (P < .03) and had higher levels of depression (P < .03) and posttraumatic stress symptomatology (P < .02) than women who had not experienced strangulation-related AIC. When controlling for potential confounding variables, including number of IPV-related traumatic brain injuries, women who had experienced strangulation also performed more poorly on a measure of working memory., Conclusion: This is the first report to assess strangulation in this manner and demonstrate links to cognitive and psychological functioning. These preliminary data contribute to our knowledge of strangulation and its effects on women who have experienced IPV., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

While initial reports have emphasized a global rise in the frequency of intimate partner violence following COVID-19, emerging data are now showing a concerning surge in the severity of COVID-19-induced physical intimate partner violence. One of the most dangerous, frequent, yet hidden consequences of severe physical intimate partner violence is acquired brain injury, including repetitive mild traumatic brain injury and hypoxic brain injury. Although the increase in high-risk physical abuse during COVID-19 is gaining recognition, what still remains absent is the urgent discussion on intimate partner violence-related acquired brain injury during these times. The potential analogous surge in intimate partner violence-related acquired brain injury may have implications for both healthcare providers and healthcare actions/policies as repeated brain injuries have been associated with residual functional deficits and chronic disability. In addition, even in the pre-pandemic times, intimate partner violence-related acquired brain injury is likely unrecognized and/or misclassified due to overlap in symptoms with other comorbid disorders. This review aimed to raise awareness about intimate partner violence-related acquired brain injury within the context of COVID-19. Health actions and policies that should be considered as part of the pandemic response to minimize adverse outcomes associated with intimate partner violence-related acquired brain injury have also been discussed., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

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.)

Compared to healthy controls (HCs), individuals with attention-deficit/hyperactivity disorder (ADHD) exhibit more symptoms of sensory processing disorder (SPD), which is associated with difficulties in educational and social activities. Most studies examining comorbid SPD-ADHD have been conducted with children and have not explored relations to brain volumes. In this pilot study, we assessed a subtype of SPD, sensory modulation disorder (SMD), and its relation to select brain volumes in adults with ADHD. We administered part of the Sensory Processing 3-Dimensions Scale (SP3D) to assess subtypes of SMD and collected structural imaging scans from 25 adults with ADHD and 29 healthy controls (HCs). Relative to HCs, subjects with ADHD scored higher on sensory craving (SC) and sensory under-responsivity (SUR) subscales. Although sensory over-responsivity (SOR) was marginally higher, this was no longer true when accounting for co-occurring anxiety. In individuals with ADHD, both SC and SUR were positively associated with amygdalar volume, SUR was also positively associated with striatal volume, whereas SOR was negatively associated with posterior ventral diencephalon volume. These preliminary findings suggest that SC and SUR may be characteristic of ADHD while SOR may be driven by co-occurring anxiety. Because different modalities were associated with different brain volumes, our findings also suggest that the modalities may involve unique neural circuits, but with a partial overlap between SC and SUR. These pilot data provide support for conducting studies examining SMD in larger samples of adults with ADHD to determine reproducibility, applicability and implications of these findings.

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.

In this report, we identify existing issues and challenges related to research on traumatic brain injury (TBI) in females and provide future directions for research. In 2017, the National Institutes of Health, in partnership with the Center for Neuroscience and Regenerative Medicine and the Defense and Veterans Brain Injury Center, hosted a workshop that focused on the unique challenges facing researchers, clinicians, patients, and other stakeholders regarding TBI in women. The goal of this "Understanding TBI in Women" workshop was to bring together researchers and clinicians to identify knowledge gaps, best practices, and target populations in research on females and/or sex differences within the field of TBI. The workshop, and the current literature, clearly highlighted that females have been underrepresented in TBI studies and clinical trials and have often been excluded (or ovariectomized) in preclinical studies. Such an absence in research on females has led to an incomplete, and perhaps inaccurate, understanding of TBI in females. The presentations and discussions centered on the existing knowledge regarding sex differences in TBI research and how these differences could be incorporated in preclinical and clinical efforts going forward. Now, a little over 2 years later, we summarize the issues and state of the science that emerged from the "Understanding TBI in Women" workshop while incorporating updates where they exist. Overall, despite some progress, there remains an abundance of research focused on males and relatively little explicitly on females., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: None

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.

Sensorimotor timing deficits are considered central to attention-deficit/hyperactivity disorder (ADHD). However, the tasks establishing timing impairments often involve interconnected processes, including low-level sensorimotor timing and higher level executive processes such as attention. Thus, the source of timing deficits in ADHD remains unclear. Low-level sensorimotor timing can be isolated from higher level processes in a finger-tapping task that examines the motor response to unexpected shifts of metronome onsets. In this study, adults with ADHD and ADHD-like symptoms (n = 25) and controls (n = 26) performed two finger-tapping tasks. The first assessed tapping variability in a standard tapping task (metronome-paced and unpaced). In the other task, participants tapped along with a metronome that contained unexpected shifts (±15, 50 ms); the timing adjustment on the tap following the shift captures pre-attentive sensorimotor timing (i.e., phase correction) and thus should be free of potential higher order confounds (e.g., attention). In the standard tapping task, as expected, the ADHD group had higher timing variability in both paced and unpaced tappings. However, in the pre-attentive task, performance did not differ between the ADHD and control groups. Together, results suggest that low-level sensorimotor timing and phase correction are largely preserved in ADHD and that some timing impairments observed in ADHD may stem from higher level factors (such as sustained attention).

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.

Background: Alcoholism has been linked to deficits in cognitive, behavioral, and emotional functions, and the cerebellum is important for optimal functioning of these abilities. However, little is known about how individual differences such as gender and drinking history might influence regional cerebellar abnormalities., Methods: Volumetric analyses of the cerebellum and its subregions were performed in relation to the interaction of gender and measures of drinking history. Structural magnetic resonance imaging scans of 44 alcoholic individuals (23 men) and 39 nonalcoholic controls (18 men) were obtained. In addition to measuring total cerebellar gray and white matter volumes, we measured 64 individual cerebellar parcellation units, as well as functionally defined a priori regions of interest that have been shown to correspond to functions impaired in alcoholism., Results: Total cerebellar white matter volume was smaller in alcoholic relative to nonalcoholic participants. Moreover, volumes of parcellation units varied with drinking history, showing negative associations between years of heavy drinking and the anterior lobe, the vestibulocerebellar lobe, and the spinocerebellar subdivision. The negative association between anterior volume and years of heavy drinking was driven primarily by alcoholic men. Additionally, we observed larger white and gray matter volumes for alcoholic women than for alcoholic men., Conclusions: The identification of drinking-related abnormalities in cerebellar subregions lays a foundation that can be utilized to inform how cerebro-cerebellar networks are perturbed in this pathological condition. These results also provide estimates of how gender and individual differences in drinking history can predict cerebellar volumes., (Copyright © 2016 by the Research Society on Alcoholism.)

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.)

Attention-deficit/hyperactivity disorder (ADHD) is increasingly understood as a disorder of spontaneous brain-network interactions. The default mode network (DMN), implicated in ADHD-linked behaviors including mind-wandering and attentional fluctuations, has been shown to exhibit abnormal spontaneous functional connectivity (FC) within-network and with other networks (salience, dorsal attention and frontoparietal) in ADHD. Although the cerebellum has been implicated in the pathophysiology of ADHD, it remains unknown whether cerebellar areas of the DMN (CerDMN) exhibit altered FC with cortical networks in ADHD. Here, 23 adults with ADHD and 23 age-, IQ-, and sex-matched controls underwent resting state fMRI. The mean time series of CerDMN areas was extracted, and FC with the whole brain was calculated. Whole-brain between-group differences in FC were assessed. Additionally, relationships between inattention and individual differences in FC were assessed for between-group interactions. In ADHD, CerDMN areas showed positive FC (in contrast to average FC in the negative direction in controls) with widespread regions of salience, dorsal attention and sensorimotor networks. ADHD individuals also exhibited higher FC (more positive correlation) of CerDMN areas with frontoparietal and visual network regions. Within the control group, but not in ADHD, participants with higher inattention had higher FC between CerDMN and regions in the visual and dorsal attention networks. This work provides novel evidence of impaired CerDMN coupling with cortical networks in ADHD and highlights a role of cerebro-cerebellar interactions in cognitive function. These data provide support for the potential targeting of CerDMN areas for therapeutic interventions in ADHD., (© 2015 Wiley Periodicals, Inc.)

Objective: Motor abnormalities, including impaired balance and increased postural sway, are commonly reported in children with ADHD, but have yet to be investigated in adults with ADHD. Furthermore, although these abnormalities are thought to stem from cerebellar deficits, evidence for an association between the cerebellum and these motor deficits has yet to be provided for either adults or children with ADHD., Method: In this study, we measured postural sway in adults with ADHD and controls, examining the relationship between sway and regional cerebellar gray matter volume. Thirty-two ADHD and 28 control participants completed various standing-posture tasks on a Wii balance board., Results: Postural sway was significantly higher for the ADHD group compared to the healthy controls. Higher sway was positively associated with regional gray matter volume in the right posterior cerebellum (lobule VIII/IX)., Conclusion: These findings show that sway abnormalities commonly reported in children with ADHD are also present in adults, and for the first time show a relationship between postural control atypicalities and the cerebellum in this group. Our findings extend the literature on motor abnormalities in ADHD and contribute to our knowledge of their neural substrate.

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.)

Although Attention-Deficit/Hyperactivity Disorder (ADHD) and Bipolar Disorder (BPD) frequently co-occur and represent a particularly morbid clinical form of both disorders, neuroimaging research addressing this comorbidity is scarce. Our aim was to evaluate cortical thickness in ADHD and BPD, testing the hypothesis that comorbid subjects (ADHD+BPD) would have neuroanatomical correlates of both disorders. Magnetic Resonance Imaging (MRI) findings were compared between 31 adults with ADHD+BPD, 18 with BPD, 26 with ADHD, and 23 healthy controls. Cortical thickness analysis of regions of interest was estimated as a function of ADHD and BPD status, using linear regression models. BPD was associated with significantly thicker cortices in 13 regions, independently of ADHD status and ADHD was associated with significantly thinner neocortical gray matter in 28 regions, independent of BPD. In the comorbid state of ADHD plus BPD, the profile of cortical abnormalities consisted of structures that are altered in both disorders individually. Results support the hypothesis that ADHD and BPD independently contribute to cortical thickness alterations of selective and distinct brain structures, and that the comorbid state represents a combinatory effect of the two. Attention to comorbidity is necessary to help clarify the heterogeneous neuroanatomy of both BPD and ADHD., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Anatomical, clinical and imaging findings suggest that the cerebellum is engaged in cognitive and affective functions as well as motor control. Evidence from converging modalities also indicates that there is a functional topography in the human cerebellum for overt control of movement vs. higher functions, such that the cerebellum can be divided into zones depending on connectivity with sensorimotor vs. multimodal association cortices. Using functional MRI, we show that regions active during overt movement differ from those involved in higher-level language, spatial processing and working memory tasks. Nine healthy participants each completed five tasks in order to determine the relative activation patterns for the different paradigms. Right-handed finger-tapping activated right cerebellar lobules IV-V and VIII, consistent with descriptions of the cerebellar homunculi. Verb generation engaged right cerebellar lobules VI-Crus I and a second cluster in lobules VIIB-VIIIA. Mental rotation activation peaks were localized to medial left cerebellar lobule VII (Crus II). A 2-back working memory task activated bilateral regions of lobules VI-VII. Viewing arousing vs. neutral images did not reliably activate the cerebellum or cerebral limbic areas in this study. The cerebellar functional topography identified in this study reflects the involvement of different cerebro-cerebellar circuits depending on the demands of the task being performed: overt movement activated sensorimotor cortices along with contralateral cerebellar lobules IV-V and VIII, whereas more cognitively demanding tasks engaged prefrontal and parietal cortices along with cerebellar lobules VI and VII. These findings provide further support for a cerebellar role in both motor and cognitive tasks, and better establish the existence of functional subregions in the cerebellum. Future studies are needed to determine the exact contribution of the cerebellum - and different cerebro-cerebellar circuits - to task performance., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.)

Although attention-deficit/hyperactivity disorder (ADHD) is associated both with brain alterations in attention and executive function (EF) circuitry and with genetic variations within the dopamine system (including the dopamine transporter gene [SLC6A3]), few studies have directly investigated how genetic variations are linked to brain alterations. We sought to examine how a polymorphism in the 3' untranslated region (UTR) of SLC6A3, associated with ADHD in meta-analysis, might contribute to variation in dorsal anterior cingulate cortex (dACC) function in subjects with ADHD. We collected fMRI scans of 42 individuals with ADHD, all of European descent and over the age of 17, while they performed the multi-source interference task (MSIT), a cognitive task shown to activate dACC. SLC6A3 3' UTR variable number tandem repeat (VNTR) polymorphisms were genotyped and brain activity was compared for groups based on allele status. ADHD individuals homozygous for the 10R allele showed significant hypoactivation in the left dACC compared to 9R-carriers. Exploratory analysis also showed trends toward hypoactivation in the 10R homozygotes in left cerebellar vermis and right lateral prefrontal cortex. Further breakdown of genotype groups showed similar activation in individuals heterozygous and homozygous for the 9R allele. Alterations in activation of attention and EF networks found previously to be involved in ADHD are likely influenced by SLC6A3 genotype. This genotype may contribute to heterogeneity of brain alterations found within ADHD samples., ((c) 2009 Wiley-Liss, Inc.)

Neuroimaging studies report cerebellar activation during both motor and non-motor paradigms, and suggest a functional topography within the cerebellum. Sensorimotor tasks activate the anterior lobe, parts of lobule VI, and lobule VIII, whereas higher-level tasks activate lobules VI and VII in the posterior lobe. To determine whether these activation patterns are evident at a single-subject level, we conducted functional magnetic resonance imaging (fMRI) during five tasks investigating sensorimotor (finger tapping), language (verb generation), spatial (mental rotation), working memory (N-back), and emotional processing (viewing images from the International Affective Picture System). Finger tapping activated the ipsilateral anterior lobe (lobules IV-V) as well as lobules VI and VIII. Activation during verb generation was found in right lobules VII and VIIIA. Mental rotation activated left-lateralized clusters in lobules VII-VIIIA, VI-Crus I, and midline VIIAt. The N-back task showed bilateral activation in right lobules VI-Crus I and left lobules VIIB-VIIIA. Cerebellar activation was evident bilaterally in lobule VI while viewing arousing vs. neutral images. This fMRI study provides the first proof of principle demonstration that there is topographic organization of motor execution vs. cognitive/emotional domains within the cerebellum of a single individual, likely reflecting the anatomical specificity of cerebro-cerebellar circuits underlying different task domains. Inter-subject variability of motor and non-motor topography remains to be determined.

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.

Attention-deficit/hyperactivity disorder (ADHD) is hypothesized to be due, in part, to structural defects in brain networks influencing cognitive, affective, and motor behaviors. Although the current literature on fiber tracts is limited in ADHD, gray matter abnormalities suggest that white matter (WM) connections may be altered selectively in neural systems. A prior study (Ashtari et al. 2005), using diffusion tensor magnetic resonance imaging (DT-MRI), showed alterations within the frontal and cerebellar WM in children and adolescents with ADHD. In this study of adults with childhood ADHD, we hypothesized that fiber pathways subserving attention and executive functions (EFs) would be altered. To this end, the cingulum bundle (CB) and superior longitudinal fascicle II (SLF II) were investigated in vivo in 12 adults with childhood ADHD and 17 demographically comparable unaffected controls using DT-MRI. Relative to controls, the fractional anisotropy (FA) values were significantly smaller in both regions of interest in the right hemisphere, in contrast to a control region (the fornix), indicating an alteration of anatomical connections within the attention and EF cerebral systems in adults with childhood ADHD. The demonstration of FA abnormalities in the CB and SLF II in adults with childhood ADHD provides further support for persistent structural abnormalities into adulthood.

Context: Previous studies have reported hypofunction, structural abnormalities, and biochemical abnormalities of the dorsal anterior midcingulate cortex (daMCC) in attention-deficit/hyperactivity disorder (ADHD). Stimulant medications are effective treatments for ADHD, but their neural effects have not been fully characterized., Objective: To determine whether the methylphenidate hydrochloride osmotic-release oral system (OROS) would increase functional magnetic resonance imaging (fMRI) activation, compared with placebo, in the daMCC and other frontoparietal regions subserving attention during the Multi-Source Interference Task (MSIT)., Design: Randomized, placebo-controlled, 6-week, before-after fMRI study., Setting: Academic medical center ambulatory clinic., Patients: Twenty-one adults with ADHD randomized to 6 weeks of treatment with methylphenidate OROS (n = 11) or placebo (n = 10)., Interventions: Patients underwent fMRI twice while performing the MSIT (scan 1 at baseline and scan 2 at 6 weeks)., Main Outcome Measures: Group-averaged, random-effects, repeated-measures, general linear model analyses were used to compare daMCC (and whole-brain) fMRI activation during the MSIT. Individual-based daMCC volume-of-interest confirmatory analyses and behavioral data are also presented., Results: Performance and baseline fMRI measures in the daMCC and other a priori brain regions did not differ between groups. Group comparisons showed a group x scan interaction and t test confirmation of higher activation in the daMCC at 6 weeks in the methylphenidate OROS group than in the placebo group (P < 1 x 10(-4), cluster corrected for multiple comparisons). Individual daMCC volume-of-interest analyses confirmed group-averaged findings and suggested that daMCC activity might be related to clinical response. Methylphenidate OROS also produced higher activation in the dorsolateral prefrontal cortex and the parietal cortex at 6 weeks., Conclusion: Methylphenidate OROS increased daMCC activation during the MSIT and may act, in part, by normalizing daMCC hypofunction in ADHD.

Background: Although there are many structural neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) in children, there are inconsistencies across studies and no consensus regarding which brain regions show the most robust area or volumetric reductions relative to control subjects. Our goal was to statistically analyze structural imaging data via a meta-analysis to help resolve these issues., Methods: We searched the MEDLINE and PsycINFO databases through January 2005. Studies must have been written in English, used magnetic resonance imaging, and presented the means and standard deviations of regions assessed. Data were extracted by one of the authors and verified independently by another author., Results: Analyses were performed using STATA with metan, metabias, and metainf programs. A meta-analysis including all regions across all studies indicated global reductions for ADHD subjects compared with control subjects, standardized mean difference=.408, p<.001. Regions most frequently assessed and showing the largest differences included cerebellar regions, the splenium of the corpus callosum, total and right cerebral volume, and right caudate. Several frontal regions assessed in only two studies also showed large significant differences., Conclusions: This meta-analysis provides a quantitative analysis of neuroanatomical abnormalities in ADHD and information that can be used to guide future studies.

Attention-deficit/hyperactivity disorder (ADHD) has been associated with structural alterations in brain networks influencing cognitive and motor behaviors. Volumetric studies in children identify abnormalities in cortical, striatal, callosal, and cerebellar regions. In a prior volumetric study, we found that ADHD adults had significantly smaller overall cortical gray matter, prefrontal, and anterior cingulate volumes than matched controls. Thickness and surface area are additional indicators of integrity of cytoarchitecture in the cortex. To expand upon our earlier results and further refine the regions of structural abnormality, we carried out a structural magnetic resonance imaging study of cortical thickness in the same sample of adults with ADHD (n = 24) and controls (n = 18), hypothesizing that the cortical networks underlying attention and executive function (EF) would be most affected. Compared with healthy adults, adults with ADHD showed selective thinning of cerebral cortex in the networks that subserve attention and EF. In the present study, we found significant cortical thinning in ADHD in a distinct cortical network supporting attention especially in the right hemisphere involving the inferior parietal lobule, the dorsolateral prefrontal, and the anterior cingulate cortices. This is the first documentation that ADHD in adults is associated with thinner cortex in the cortical networks that modulate attention and EF.

Objectives: Gray and white matter volume deficits have been reported in a number of studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural magnetic resonance imaging (MRI) studies of adults with ADHD. This structural MRI study used an a priori region of interest approach., Methods: Twenty-four adults with DSM-IV ADHD and 18 healthy controls comparable on age, socioeconomic status, sex, handedness, education, IQ, and achievement test performance had an MRI on a 1.5T Siemens scanner. Cortical and sub-cortical gray and white matter were segmented. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere. Based on a priori hypotheses we focused on prefrontal, anterior cingulate cortex (ACC) and overall gray matter volumes. General linear analyses of the volumes of brain regions, adjusting for age, sex, and total cerebral volumes, were used to compare groups., Results: Relative to controls, ADHD adults had significantly smaller overall cortical gray matter, prefrontal and ACC volumes., Conclusions: Adults with ADHD have volume differences in brain regions in areas involved in attention and executive control. These data, largely consistent with studies of children, support the idea that adults with ADHD have a valid disorder with persistent biological features.

We describe an MRI-based system for topological analysis followed by measurements of topographic features for the human cerebral cortex that takes as its starting point volumetric segmentation data. This permits interoperation between volume-based and surface-based topographic analysis and extends the functionality of many existing segmentation schemes. We demonstrate the utility of these operations in individual as well as to group analysis. The methodology integrates analyses of cortical segmentation data generated by manual and semi-automated volumetric morphometry routines (such as the program cardviews) with the procedures of the FreeSurfer program to generate a cortical ribbon of the cerebrum and perform cortical topographic measurements (including thickness, surface area and curvature) in individual subjects as well as in subject populations. This system allows the computation of topographical cortical measurements for segmentation data generated from manual and semi-automated volumetric sources other than FreeSurfer. These measurements can be regionally specific and integrated with systems of cortical parcellation that subdivides the neocortex into gyral-based parcellation units (PUs). This system of topographical analysis of the cerebral cortex is consistent with current views of cortical development and neural systems organization of the human and non-human primate brain.

The authors' goal was to assess neuropsychological performance in girls with attention-deficit/hyperactivity disorder (ADHD) and evaluate the role of comorbid learning disabilities (LDs). Participants were 140 girls with ADHD and 122 girls without ADHD, ages 6-17 years. Neuropsychological performance was measured in a standardized manner, blind to clinical status. LD was defined by a combined regression-based and low-achievement classification. ADHD was associated with modest, but significant, neuropsychological impairment, as measured with an aggregate measure of performance and with the Stroop Color-Word Test, independent of age, social class, IQ, and psychiatric comorbidity. Neuropsychological deficits were most pronounced in girls with both ADHD and an LD and in those without medications. These results extend to females the previously documented association of LDs with neuropsychological functioning in males with ADHD.

Over the past few decades, functional neuroimaging techniques have begun to provide unprecedented windows on the neurobiology of attention-deficit/hyperactivity disorder (ADHD) and the neural effects of medications used to treat the disorder. Convergent data from neuroimaging, neuropsychological, genetics, and neurochemical studies have implicated dysfunction of fronto-striatal structures (lateral prefrontal cortex, dorsal anterior cingulate cortex, caudate, and putamen) as likely contributing to the pathophysiology of ADHD. This review 1) provides an overview of the main imaging techniques being used to study ADHD; 2) discusses their relative strengths and weaknesses, highlighting how they can complement one another; 3) shows how the functional imaging literature, which has built on the structural imaging data, is now being used to test focused hypotheses regarding the neurobiological substrate of ADHD; and 4) suggests guidelines for improving future functional imaging studies. Although at present there are no accepted uses for functional imaging in diagnosing ADHD, this article mentions possible future clinical uses of imaging in 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.

Background: Attention-deficit/hyperactivity disorder (ADHD) in adults is an increasingly recognized psychiatric disorder, linked with impairments in numerous life domains and with neurocognitive dysfunctions. However, the neural substrate of cognitive functioning in adults with this disorder has been relatively unexamined. The objective of this study was to examine neural functioning in ADHD adults during performance on a verbal working memory task., Methods: A sample of unmedicated adults with ADHD (n = 20) and control subjects (n = 20) performed a 2-back task of working memory, and the blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) response was used as a measure of neural activity during working memory performance., Results: Though working memory performance did not differ significantly between ADHD adults and control subjects, ADHD adults showed significantly decreased activity in cerebellar and occipital regions and a trend toward decreased activation in an a priori predicted region of the prefrontal cortex., Conclusions: ADHD adults showed altered patterns of neural activity despite comparable performance on a verbal working memory task. These findings suggest that the cerebellum is involved in the pathophysiology of at least some cognitive deficits associated with ADHD and emphasize the need for additional research aimed at elucidating the role of the cerebellum in ADHD symptomatology.

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.

The goals of the present study were to examine (a) whether battered women in a sample of both shelter and nonshelter women are sustaining brain injuries from their partners and (b) if so, whether such brain injuries are associated with partner abuse severity, cognitive functioning, or psychopathology. Ninety-nine battered women were assessed using neuropsychological, psychopathology, and abuse history measures. Almost three quarters of the sample sustained at least 1 partner-related brain injury and half sustained multiple partner-related brain injuries. Further, in a subset of women (n = 57), brain injury severity was negatively associated with measures of memory, learning, and cognitive flexibility and was positively associated with partner abuse severity, general distress, anhedonic depression, worry, anxious arousal, and posttraumatic stress disorder symptomatology.

In a sample of 75 women recruited from the community, we measured trauma/maltreatment history and symptoms of schizotypal personality disorder, using both questionnaire and interview measures. As hypothesized, individuals with histories of trauma/maltreatment had elevated levels of schizotypal symptoms. Among types of trauma/maltreatment, reported childhood neglect was especially strongly associated with schizotypal symptoms. Although posttraumatic stress disorder symptom severity, depression, dissociation, and difficulty identifying one's emotions were all associated with schizotypal symptoms, they could not account completely for the association between trauma/maltreatment and schizotypal symptoms.

Background: Factors contributing to the development of alexithymia and the nature of alexithymia's relation with trait negative and positive affectivity are unclear. In this study, a twin approach was used to examine the degree of genetic and environmental contributions to the different facets of alexithymia, and the nature of their relations to trait negative and positive affectivity., Method: Forty-five monozygotic and 32 same-sex dizygotic twin pairs completed the Toronto Alexithymia Scale-20, the Eysenck Personality Inventory, and a zygosity questionnaire., Results: Model fitting analyses indicated that familial influences contributed significantly to all three facets of alexithymia. Parameter estimates and intraclass correlations suggested, though could not confirm, that it was shared environmental factors that contributed to difficulty identifying and communicating emotions (ID and COM), but shared genetic factors that contributed to externally oriented thinking (EOT). Between-twin cross-trait twin analyses revealed strong correlations between ID and neuroticism, and between COM and extraversion, and suggested that it is shared familial influences which account for these associations., Conclusions: The results of this study indicate that: (a) the different facets of alexithymia are influenced by familial factors; (b) the previously noted associations between ID and COM and trait affectivity are not merely methodological artifacts; and (c) the associations between ID and COM and trait affectivity are influenced by familial factors. The results also suggest that ID and COM are largely influenced by shared environmental factors, but that EOT is influenced by genetic factors., (Copyright 2001 S. Karger AG, Basel.)