Neural Systems for Own-body Processing Align with Gender Identity Rather Than Birth-assigned Sex.

Gender identity is a core aspect of self-identity and is usually congruent with birth-assigned sex and own body sex-perception. The neuronal circuits underlying gender identity are unknown, but greater awareness of transgenderism has sparked interest in studying these circuits. We did this by comparing brain activation and connectivity in transgender individuals (for whom gender identity and birth-assigned sex are incongruent) with that in cisgender controls (for whom they are congruent) when performing a body self-identification task during functional magnetic resonance imaging. Thirty transgender and 30 cisgender participants viewed images of their own bodies and bodies morphed in sex toward or opposite to birth-assigned sex, rating each image to the degree they identified with it. While controls identified with images of themselves, transgender individuals identified with images morphed "opposite" to their birth-assigned sex. After covarying out the effect of self-similarity ratings, both groups activated similar self- and body-processing systems when viewing bodies that aligned with their gender identity rather than birth-assigned sex. Additionally, transgender participants had greater limbic involvement when viewing ambiguous, androgynous images of themselves morphed toward their gender identity. These results shed light on underlying self-processing networks specific to gender identity and uncover additional involvement of emotional processing in transgender individuals.

Multivariate resting-state functional connectivity predicts response to cognitive behavioral therapy in obsessive-compulsive disorder.

Cognitive behavioral therapy (CBT) is an effective treatment for many with obsessive-compulsive disorder (OCD). However, response varies considerably among individuals. Attaining a means to predict an individual's potential response would permit clinicians to more prudently allocate resources for this often stressful and time-consuming treatment. We collected resting-state functional magnetic resonance imaging from adults with OCD before and after 4 weeks of intensive daily CBT. We leveraged machine learning with cross-validation to assess the power of functional connectivity (FC) patterns to predict individual posttreatment OCD symptom severity. Pretreatment FC patterns within the default mode network and visual network significantly predicted posttreatment OCD severity, explaining up to 67% of the variance. These networks were stronger predictors than pretreatment clinical scores. Results have clinical implications for developing personalized medicine approaches to identifying individual OCD patients who will maximally benefit from intensive CBT.

Sex differences in own and other body perception.

Own body perception, and differentiating and comparing one's body to another person's body, are common cognitive functions that have relevance for self-identity and social interactions. In several psychiatric conditions, including anorexia nervosa, body dysmorphic disorder, gender dysphoria, and autism spectrum disorder, self and own body perception, as well as aspects of social communication are disturbed. Despite most of these conditions having skewed prevalence sex ratios, little is known about whether the neural basis of own body perception differs between the sexes. We addressed this question by investigating brain activation using functional magnetic resonance imaging during a Body Perception task in 15 male and 15 female healthy participants. Participants viewed their own body, bodies of same-sex, or opposite-sex other people, and rated the degree that they appeared like themselves. We found that men and women did not differ in the pattern of brain activation during own body perception compared to a scrambled control image. However, when viewing images of other bodies of same-sex or opposite-sex, men showed significantly stronger activations in attention-related and reward-related brain regions, whereas women engaged stronger activations in striatal, medial-prefrontal, and insular cortices, when viewing the own body compared to other images of the opposite sex. It is possible that other body images, particularly of the opposite sex, may be of greater salience for men, whereas images of own bodies may be more salient for women. These observations provide tentative neurobiological correlates to why women may be more vulnerable than men to conditions involving own body perception.

Appearance evaluation of others' faces and bodies in anorexia nervosa and body dysmorphic disorder.

OBJECTIVE: Individuals with anorexia nervosa (AN) and body dysmorphic disorder (BDD) exhibit distorted perception and negative evaluations of their own appearance; however, little is known about how they perceive others' appearance, and whether or not the conditions share perceptual distortions. METHOD: Thirty participants with BDD, 22 with AN, now weight-restored, and 39 healthy comparison participants (HC) rated photographs of others' faces and bodies on attractiveness, how overweight or underweight they were, and how much photographs triggered thoughts of their own appearance. We compared responses among groups by stimulus type and by level-of-detail (spatial frequency). RESULTS: Compared to HCs, AN and BDD had lower attractiveness ratings for others' bodies and faces for high-detail and low-detail images, rated bodies as more overweight, and were more triggered to think of their own appearance for faces and bodies. In AN, symptom severity was associated with greater triggering of thoughts of own appearance and higher endorsement of overweight ratings for bodies. In BDD, symptom severity was associated with greater triggering of thoughts of own appearance for bodies and higher overweight ratings for low-detail images. BDD was more triggered to think of own facial appearance than AN. DISCUSSION: AN and BDD show similar behavioral phenotypes of negative appearance evaluations for others' faces and bodies, and have thoughts of their own appearance triggered even for images outside of their primary appearance concerns, suggesting a more complex cross-disorder body-image phenotype than previously assumed. Future treatment strategies may benefit from addressing how these individuals evaluate others in addition to themselves. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:127-138).

Differences in resting corticolimbic functional connectivity in bipolar I euthymia.

OBJECTIVE: We examined resting state functional connectivity in the brain between key emotion regulation regions in bipolar I disorder to delineate differences in coupling from healthy subjects. METHODS: Euthymic subjects with bipolar I disorder (n = 20) and matched healthy subjects (n = 20) participated in a resting state functional magnetic resonance imaging scan. Low-frequency fluctuations in blood oxygen level-dependent (BOLD) signal were correlated in the six connections between four anatomically defined nodes: left and right amygdala and left and right ventrolateral prefrontal cortex (vlPFC). Seed-to-voxel connectivity results were probed for commonly coupled regions. Following this, an identified region was included in a mediation analysis to determine the potential of mediation. RESULTS: The bipolar I disorder group exhibited significant hyperconnectivity between right amygdala and right vlPFC relative to healthy subjects. The connectivity between these regions in the bipolar I disorder group was partially mediated by activity in the anterior cingulate cortex (ACC). CONCLUSIONS: Greater coupling between right amygdala and right vlPFC and their partial mediation by the ACC were found in bipolar I disorder subjects in remission and in the absence of a psychological task. These findings have implications for a trait-related and clinically important imaging biomarker.

Deficits in inferior frontal cortex activation in euthymic bipolar disorder patients during a response inhibition task.

OBJECTIVES: The inferior frontal cortical-striatal network plays an integral role in response inhibition in normal populations. While inferior frontal cortex (IFC) impairment has been reported in mania, this study explored whether this dysfunction persists in euthymia. METHODS: Functional magnetic resonance imaging (fMRI) activation was evaluated in 32 euthymic patients with bipolar I disorder and 30 healthy subjects while performing the Go/NoGo response inhibition task. Behavioral data were collected to evaluate accuracy and response time. Within-group and between-group comparisons of activation were conducted using whole-brain analyses to probe significant group differences in neural function. RESULTS: Both groups activated bilateral IFC. However, between-group comparisons showed a significantly reduced activation in this brain region in euthymic patients with bipolar disorder compared to healthy subjects. Other frontal and basal ganglia regions involved in response inhibition were additionally significantly reduced in bipolar disorder patients, in both the medicated and the unmedicated subgroups. No areas of greater activation were observed in bipolar disorder patients versus healthy subjects. CONCLUSIONS: Bipolar disorder patients, even during euthymia, have a persistent reduction in activation of brain regions involved in response inhibition, suggesting that reduced activation in the orbitofrontal cortex and striatum is not solely related to the state of mania. These findings may represent underlying trait abnormalities in bipolar disorder.

Beta-adrenergic receptor activation rescues theta frequency stimulation-induced LTP deficits in mice expressing C-terminally truncated NMDA receptor GluN2A subunits.

Through protein interactions mediated by their cytoplasmic C termini the GluN2A and GluN2B subunits of NMDA receptors (NMDARs) have a key role in the formation of NMDAR signaling complexes at excitatory synapses. Although these signaling complexes are thought to have a crucial role in NMDAR-dependent forms of synaptic plasticity such as long-term potentiation (LTP), the role of the C terminus of GluN2A in coupling NMDARs to LTP enhancing and/or suppressing signaling pathways is unclear. To address this issue we examined the induction of LTP in the hippocampal CA1 region in mice lacking the C terminus of endogenous GluN2A subunits (GluN2AΔC/ΔC). Our results show that truncation of GluN2A subunits produces robust, but highly frequency-dependent, deficits in LTP and a reduction in basal levels of extracellular signal regulated kinase 2 (ERK2) activation and phosphorylation of AMPA receptor GluA1 subunits at a protein kinase A site (serine 845). Consistent with the notion that these signaling deficits contribute to the deficits in LTP in GluN2AΔC/ΔC mice, activating ERK2 and increasing GluA1 S845 phosphorylation through activation of ß-adrenergic receptors rescued the induction of LTP in these mutants. Together, our results indicate that the capacity of excitatory synapses to undergo plasticity in response to different patterns of activity is dependent on the coupling of specific signaling pathways to the intracellular domains of the NMDARs and that abnormal plasticity resulting from mutations in NMDARs can be reduced by activation of key neuromodulatory transmitter receptors that engage converging signaling pathways.

Dynamic Effective Connectivity Patterns During Rapid Face Stimuli Presentation in Body Dysmorphic Disorder.

In individuals with body dysmorphic disorder (BDD), perceptual appearance distortions may be related to imbalances in global vs. local visual processing. Understanding the mechanistic brain effects of potential interventions is crucial for rational treatment development. The dorsal visual stream (DVS) is tuned to rapid image presentation, facilitating global/holistic processing, whereas the ventral visual stream (VVS), responsible for local/detailed processing, reduces activation magnitude with shorter stimulus duration. This study tested a strategy of rapid, short-duration face presentation on visual system connectivity. Thirty-eight unmedicated adults with BDD and 29 healthy controls viewed photographs of their faces for short (125 ms, 250 ms, 500 ms) and long (3000 ms) durations during fMRI scan. Dynamic effective connectivity in DVS and VVS was analyzed. BDD individuals exhibited weaker connectivity from occipital to parietal DVS areas than controls for all stimuli durations. Short compared with long viewing durations (125 ms vs. 3,000 ms and 500 ms vs. 3,000 ms) resulted in significantly weaker VVS connectivity from calcarine cortex to inferior occipital gyri in controls; however, there was only a trend for similar results in BDD. The DVS to VVS ratio, representing a balance between global and local processing, incrementally increased with shorter viewing durations in BDD, although it was not statistically significant. In sum, visual systems in those with BDD are not as responsive as in controls to rapid face presentation. Whether rapid face presentation could reduce connectivity in visual systems responsible for local/detailed processing in BDD may necessitate different parameters or strategies. These results provide mechanistic insights for perceptual retraining treatment designs.

Mesolimbic Neurobehavioral Mechanisms of Reward Motivation in Anorexia Nervosa: A Multimodal Imaging Study.

Diminished motivation to pursue and obtain primary and secondary rewards has been demonstrated in anorexia nervosa (AN). However, the neurobehavioral mechanisms underlying the behavioral activation component of aberrant reward motivation remains incompletely understood. This work aims to explore this underexplored facet of reward motivation in AN. We recruited female adolescents with AN, restricting type (n = 32) and a healthy control group (n = 28). All participants underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. Diffusion MRI data was also collected to examine the reward motivation circuit's structural connectivity. Behavioral results demonstrated slower speed of reward-seeking behavior in those with AN compared with controls. Accompanying this was lower functional connectivity and reduced white matter structural integrity of the connection between the ventral tegmental area/substantia nigra pars compacta and the nucleus accumbens within the mesolimbic circuit. Further, there was evidence of neurobehavioral decoupling in AN between reward-seeking behavior and mesolimbic regional activation and functional connectivity. Aberrant activity of the bed nucleus of the stria terminalis (BNST) and its connectivity with the mesolimbic system was also evident in AN during the reward motivation period. Our findings suggest functional and structural dysconnectivity within a mesolimbic reward circuit, neurofunctional decoupling from reward-seeking behavior, and abnormal BNST function and circuit interaction with the mesolimbic system. These results show behavioral indicators of aberrant reward motivation in AN, particularly in its activational component. This is mediated neuronally by mesolimbic reward circuit functional and structural dysconnectivity as well as neurobehavioral decoupling. Based on these findings, we suggest a novel circuit-based mechanism of impaired reward processing in AN, with the potential for translation to developing more targeted and effective treatments in this difficult-to-treat psychiatric condition.

Amygdala reactivity in healthy adults is correlated with prefrontal cortical thickness.

Recent evidence suggests that putting feelings into words activates the prefrontal cortex (PFC) and suppresses the response of the amygdala, potentially helping to alleviate emotional distress. To further elucidate the relationship between brain structure and function in these regions, structural and functional magnetic resonance imaging (MRI) data were collected from a sample of 20 healthy human subjects. Structural MRI data were processed using cortical pattern-matching algorithms to produce spatially normalized maps of cortical thickness. During functional scanning, subjects cognitively assessed an emotional target face by choosing one of two linguistic labels (label emotion condition) or matched geometric forms (control condition). Manually prescribed regions of interest for the left amygdala were used to extract percentage signal change in this region occurring during the contrast of label emotion versus match forms. A correlation analysis between left amygdala activation and cortical thickness was then performed along each point of the cortical surface, resulting in a color-coded r value at each cortical point. Correlation analyses revealed that gray matter thickness in left ventromedial PFC was inversely correlated with task-related activation in the amygdala. These data add support to a general role of the ventromedial PFC in regulating activity of the amygdala.

Explicit and implicit memory in late-life depression.

OBJECTIVE: Late-life depression has been associated with memory loss and is frequently assumed to be a risk factor for continued cognitive decline. This study examined cognition in patients with late-life depression with a focus on the assessment of the extent and type of memory loss among elderly depressed patients. METHODS: Two-year cross-sectional study of elderly depressed (N = 112) and nondepressed (N = 138) individuals at or older than 60 years in an urban area surrounding a major medical center in southern California. Participants had little to moderate stroke risk. Volunteers were screened with the Hamilton Depression Rating Scale and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I Disorders. Patients were diagnosed for major depression by a geriatric psychiatrist using DSM-IV criteria. Volunteers completed neuropsychological testing, a standard battery of laboratory tests, and a neurologic and psychiatric evaluation to rule out a medical burden that might contribute to depression or early dementia. RESULTS: Depressed patients showed deficits in attention and processing, executive function, and immediate explicit recall. Implicit learning and episodic recall of the testing procedure, semantic and phonetic fluency, and retention of newly acquired verbal material after a delay period were comparable with controls. CONCLUSION: Moderately depressed patients demonstrate a pattern of cognitive deficits suggestive of mild frontal dysfunction during recall tasks. Their retention of material over a delay period and their intact language skills indicate medial hippocampal function similar to controls. Subcortically mediated implicit memory is also at normal levels. These findings support current efforts to identify pathways of frontal and/or striatal compromise during depressive episodes.

Common and dissociable prefrontal loci associated with component mechanisms of analogical reasoning.

The ability to draw analogies requires 2 key cognitive processes, relational integration and resolution of interference. The present study aimed to identify the neural correlates of both component processes of analogical reasoning within a single, nonverbal analogy task using event-related functional magnetic resonance imaging. Participants verified whether a visual analogy was true by considering either 1 or 3 relational dimensions. On half of the trials, there was an additional need to resolve interference in order to make a correct judgment. Increase in the number of dimensions to integrate was associated with increased activation in the lateral prefrontal cortex as well as lateral frontal pole in both hemispheres. When there was a need to resolve interference during reasoning, activation increased in the lateral prefrontal cortex but not in the frontal pole. We identified regions in the middle and inferior frontal gyri which were exclusively sensitive to demands on each component process, in addition to a partial overlap between these neural correlates of each component process. These results indicate that analogical reasoning is mediated by the coordination of multiple regions of the prefrontal cortex, of which some are sensitive to demands on only one of these 2 component processes, whereas others are sensitive to both.

Predicting outcomes of cross-sex hormone therapy in transgender individuals with gender incongruence based on pre-therapy resting-state brain connectivity.

Individuals with gender incongruence (GI) experience serious distress due to incongruence between their gender identity and birth-assigned sex. Sociological, cultural, interpersonal, and biological factors are likely contributory, and for some individuals medical treatment such as cross-sex hormone therapy and gender-affirming surgery can be helpful. Cross-sex hormone therapy can be effective for reducing body incongruence, but responses vary, and there is no reliable way to predict therapeutic outcomes. We used clinical and MRI data before cross-sex hormone therapy as features to train a machine learning model to predict individuals' post-therapy body congruence (the degree to which photos of their bodies match their self-identities). Twenty-five trans women and trans men with gender incongruence participated. The model significantly predicted post-therapy body congruence, with the highest predictive features coming from the cingulo-opercular (R2 = 0.41) and fronto-parietal (R2 = 0.30) networks. This study provides evidence that hormone therapy efficacy can be predicted from information collected before therapy, and that patterns of functional brain connectivity may provide insights into body-brain effects of hormones, affecting one's sense of body congruence. Results could help identify the need for personalized therapies in individuals predicted to have low body-self congruence after standard therapy.

Brain activation and connectivity in anorexia nervosa and body dysmorphic disorder when viewing bodies: relationships to clinical symptoms and perception of appearance.

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted perception of appearance, yet no studies have directly compared the neurobiology associated with body perception. We compared AN and BDD in brain activation and connectivity in relevant networks when viewing images of others' bodies and tested their relationships with clinical symptoms and subjective appearance evaluations. We acquired fMRI data from 64 unmedicated females (20 weight-restored AN, 23 BDD, 21 controls) during a matching task using unaltered or spatial-frequency filtered photos of others' bodies. Using general linear model and independent components analyses we compared brain activation and connectivity in visual, striatal, and parietal networks and performed univariate and partial least squares multivariate analyses to investigate relationships with clinical symptoms and appearance evaluations. AN and BDD showed partially overlapping patterns of hyperconnectivity in the dorsal visual network and hypoconnectivity in parietal network compared with controls. BDD, but not AN, demonstrated hypoactivity in dorsal visual and parietal networks compared to controls. Further, there were significant activity and connectivity differences between AN and BDD in both networks. In both groups, activity and/or connectivity were associated with symptom severity and appearance ratings of others' bodies. Thus, AN and BDD demonstrate both distinct and partially-overlapping aberrant neural phenotypes involved in body processing and visually encoding global features. Nevertheless, in each disorder, aberrant activity and connectivity show relationships to clinically relevant symptoms and subjective perception. These results have implications for understanding distinct and shared pathophysiology underlying perceptual distortions of appearance and may inform future novel treatment strategies.

Brain health consequences of digital technology use
.

Emerging scientific evidence indicates that frequent digital technology use has a significant impact-both negative and positive-on brain function and behavior. Potential harmful effects of extensive screen time and technology use include heightened attention-deficit symptoms, impaired emotional and social intelligence, technology addiction, social isolation, impaired brain development, and disrupted sleep. However, various apps, videogames, and other online tools may benefit brain health. Functional imaging scans show that internet-naive older adults who learn to search online show significant increases in brain neural activity during simulated internet searches. Certain computer programs and videogames may improve memory, multitasking skills, fluid intelligence, and other cognitive abilities. Some apps and digital tools offer mental health interventions providing self-management, monitoring, skills training, and other interventions that may improve mood and behavior. Additional research on the positive and negative brain health effects of technology is needed to elucidate mechanisms and underlying causal relationships.
.

La evidencia científica que está surgiendo muestra que el empleo frecuente de la tecnología digital tiene un impacto significativo, tanto negativo como positivo, en la función cerebral y en el comportamiento. Los posibles efectos nocivos del tiempo prolongado frente a la pantalla y del empleo de la tecnología incluyen síntomas como marcado déficit de atención, deterioro de la inteligencia emocional y social, adicción a la tecnología, aislamiento social, deterioro del desarrollo cerebral y alteraciones del sueño. Sin embargo, hay varias aplicaciones, videojuegos y otras herramientas en línea que pueden beneficiar la salud del cerebro. En las imágenes cerebrales funcionales se ha observado que los adultos mayores vírgenes a internet que aprenden a buscar en línea, muestran aumentos significativos en la actividad neuronal cerebral durante las búsquedas simuladas en internet. Ciertos programas computacionales y videojuegos pueden mejorar la memoria, las destrezas en tareas múltiples, la fluidez de la inteligencia y otras habilidades cognitivas. Hay varias aplicaciones y herramientas digitales que ofrecen intervenciones en salud mental y que proporcionan automanejo, monitoreo, capacitación junto a otras intervenciones que pueden mejorar el estado de ánimo y el comportamiento. Se require de investigación adicional acerca de los efectos positivos y negativos de la tecnología sobre la salud del cerebro para dilucidar los mecanismos y las relaciones causales subyacentes.

D'après de nouvelles données scientifiques, l'usage fréquent des technologies numériques influe significativement sur le comportement et le fonctionnement cérébral, de façon aussi bien négative que positive. Une pratique excessive des écrans et des technologies numériques peut avoir des effets néfastes comme des symptômes de déficit d'attention, une intelligence émotionnelle et sociale altérée, une dépendance à la technologie, un isolement social, un développement cérébral dégradé et des troubles du sommeil. Cependant, certaines applications, jeux vidéo et autres outils en ligne peuvent avoir des effets bénéfiques sur le cerveau. L'imagerie fonctionnelle montre une activité neuronale significativement augmentée chez des personnes âgées jamais exposées à Internet et qui apprennent à faire des recherches en ligne. Certains programmes informatiques et jeux vidéo peuvent améliorer la mémoire, les compétences multitâches, l'agilité de l'intelligence et d'autres capacités cognitives. Dans le domaine de la santé mentale, différents outils et applications numériques permettant l'autogestion, le suivi, l'acquisition de compétences et d'autres techniques sont susceptibles d'améliorer l'humeur et le comportement du patient. Les effets positifs et négatifs de la technologie sur la santé cérébrale nécessitent d'être encore étudiés afin d'en mieux comprendre les mécanismes et les relations de cause à effet.

Your brain on Google: patterns of cerebral activation during internet searching.

OBJECTIVE: Previous research suggests that engaging in mentally stimulating tasks may improve brain health and cognitive abilities. Using computer search engines to find information on the Internet has become a frequent daily activity of people at any age, including middle-aged and older adults. As a preliminary means of exploring the possible influence of Internet experience on brain activation patterns, the authors performed functional magnetic resonance imaging (MRI) of the brain in older persons during search engine use and explored whether prior search engine experience was associated with the pattern of brain activation during Internet use. DESIGN: Cross-sectional, exploratory observational study PARTICIPANTS: The authors studied 24 subjects (age, 55-76 years) who were neurologically normal, of whom 12 had minimal Internet search engine experience (Net Naive group) and 12 had more extensive experience (Net Savvy group). The mean age and level of education were similar in the two groups. MEASUREMENTS: Patterns of brain activation during functional MRI scanning were determined while subjects performed a novel Internet search task, or a control task of reading text on a computer screen formatted to simulate the prototypic layout of a printed book, where the content was matched in all respects, in comparison with a nontext control task. RESULTS: The text reading task activated brain regions controlling language, reading, memory, and visual abilities, including left inferior frontal, temporal, posterior cingulate, parietal, and occipital regions, and both the magnitude and the extent of brain activation were similar in the Net Naive and Net Savvy groups. During the Internet search task, the Net Naive group showed an activation pattern similar to that of their text reading task, whereas the Net Savvy group demonstrated significant increases in signal intensity in additional regions controlling decision making, complex reasoning, and vision, including the frontal pole, anterior temporal region, anterior and posterior cingulate, and hippocampus. Internet searching was associated with a more than twofold increase in the extent of activation in the major regional clusters in the Net Savvy group compared with the Net Naive group (21,782 versus 8,646 total activated voxels). CONCLUSION: Although the present findings must be interpreted cautiously in light of the exploratory design of this study, they suggest that Internet searching may engage a greater extent of neural circuitry not activated while reading text pages but only in people with prior computer and Internet search experience. These observations suggest that in middle-aged and older adults, prior experience with Internet searching may alter the brain's responsiveness in neural circuits controlling decision making and complex reasoning.

Differentiating weight-restored anorexia nervosa and body dysmorphic disorder using neuroimaging and psychometric markers.

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are potentially life-threatening conditions whose partially overlapping phenomenology-distorted perception of appearance, obsessions/compulsions, and limited insight-can make diagnostic distinction difficult in some cases. Accurate diagnosis is crucial, as the effective treatments for AN and BDD differ. To improve diagnostic accuracy and clarify the contributions of each of the multiple underlying factors, we developed a two-stage machine learning model that uses multimodal, neurobiology-based, and symptom-based quantitative data as features: task-based functional magnetic resonance imaging data using body visual stimuli, graph theory metrics of white matter connectivity from diffusor tensor imaging, and anxiety, depression, and insight psychometric scores. In a sample of unmedicated adults with BDD (n = 29), unmedicated adults with weight-restored AN (n = 24), and healthy controls (n = 31), the resulting model labeled individuals with an accuracy of 76%, significantly better than the chance accuracy of 35% ([Formula: see text]). In the multivariate model, reduced white matter global efficiency and better insight were associated more with AN than with BDD. These results improve our understanding of the relative contributions of the neurobiological characteristics and symptoms of these disorders. Moreover, this approach has the potential to aid clinicians in diagnosis, thereby leading to more tailored therapy.

Aberrant Dynamic Connectivity for Fear Processing in Anorexia Nervosa and Body Dysmorphic Disorder.

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) share distorted perceptions of appearance with extreme negative emotion, yet the neural phenotypes of emotion processing remain underexplored in them, and they have never been directly compared. We sought to determine if shared and disorder-specific fronto-limbic connectivity patterns characterize these disorders. FMRI data was obtained from three unmedicated groups: BDD (n = 32), weight-restored AN (n = 25), and healthy controls (HC; n = 37), while they viewed fearful faces and rated their own degree of fearfulness in response. We performed dynamic effective connectivity modeling with medial prefrontal cortex (mPFC), rostral anterior cingulate cortex (rACC), and amygdala as regions-of-interest (ROI), and assessed associations between connectivity and clinical variables. HCs exhibited significant within-group bidirectional mPFC-amygdala connectivity, which increased across the blocks, whereas BDD participants exhibited only significant mPFC-to-amygdala connectivity (P < 0.05, family-wise error corrected). In contrast, participants with AN lacked significant prefrontal-amygdala connectivity in either direction. AN showed significantly weaker mPFC-to-amygdala connectivity compared to HCs (P = 0.0015) and BDD (P = 0.0050). The mPFC-to-amygdala connectivity was associated with greater subjective fear ratings (R2 = 0.11, P = 0.0016), eating disorder symptoms (R2 = 0.33, P = 0.0029), and anxiety (R2 = 0.29, P = 0.0055) intensity scores. Our findings, which suggest a complex nosological relationship, have implications for understanding emotion regulation circuitry in these related psychiatric disorders, and may have relevance for current and novel therapeutic approaches.

Pregenual Anterior Cingulate Dysfunction Associated with Depression in OCD: An Integrated Multimodal fMRI/1H MRS Study.

Depression is a commonly occurring symptom in obsessive-compulsive disorder (OCD), and is associated with worse functional impairment, poorer quality of life, and poorer treatment response. Understanding the underlying neurochemical and connectivity-based brain mechanisms of this important symptom domain in OCD is necessary for development of novel, more globally effective treatments. To investigate biopsychological mechanisms of comorbid depression in OCD, we examined effective connectivity and neurochemical signatures in the pregenual anterior cingulate cortex (pACC), a structure known to be involved in both OCD and depression. Resting-state functional magnetic resonance imaging (fMRI) and 1H magnetic resonance spectroscopy (MRS) data were obtained from participants with OCD (n=49) and healthy individuals of equivalent age and sex (n=25). Granger causality-based effective (directed) connectivity was used to define causal networks involving the right and left pACC. The interplay between fMRI connectivity, 1H MRS and clinical data was explored by applying moderation and mediation analyses. We found that the causal influence of the right dorsal anterior midcingulate cortex (daMCC) on the right pACC was significantly lower in the OCD group and showed significant correlation with depressive symptom severity in the OCD group. Lower and moderate levels of glutamate (Glu) in the right pACC significantly moderated the interaction between right daMCC-pACC connectivity and depression severity. Our results suggest a biochemical-connectivity-psychological model of pACC dysfunction contributing to depression in OCD, particularly involving intracingulate connectivity and glutamate levels in the pACC. These findings have implications for potential molecular and network targets for treatment of this multi-faceted psychiatric condition.

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease.

In neuroimaging, functional magnetic resonance imaging (fMRI) measures the blood-oxygenation-level dependent (BOLD) signal in the brain. The degree of correlation of the BOLD signal in spatially independent regions of the brain defines the functional connectivity of those regions. During a cognitive fMRI task, a psychophysiological interaction (PPI) analysis can be used to examine changes in the functional connectivity during specific contexts defined by the cognitive task. An example of such a task is one that engages the memory system, asking participants to learn pairs of unrelated words (encoding) and recall the second word in a pair when presented with the first word (retrieval). In the present study, we used this type of associative memory task and a generalized PPI (gPPI) analysis to compare changes in hippocampal connectivity in older adults who are carriers of the Alzheimer's disease (AD) genetic risk factor apolipoprotein-E epsilon-4 (APOEε4). Specifically, we show that the functional connectivity of subregions of the hippocampus changes during encoding and retrieval, the two active phases of the associative memory task. Context-dependent changes in functional connectivity of the hippocampus were significantly different in carriers of APOEε4 compared to non-carriers. PPI analyses make it possible to examine changes in functional connectivity, distinct from univariate main effects, and to compare these changes across groups. Thus, a PPI analysis may reveal complex task effects in specific cohorts that traditional univariate methods do not capture. PPI analyses cannot, however, determine directionality or causality between functionally connected regions. Nevertheless, PPI analyses provide powerful means for generating specific hypotheses regarding functional relationships, which can be tested using causal models. As the brain is increasingly described in terms of connectivity and networks, PPI is an important method for analyzing fMRI task data that is in line with the current conception of the human brain.