The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen’s d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen’s d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level

The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T-1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status

Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders: findings from the ENIGMA ADHD, ASD, and OCD Working Groups

Objective Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders. Methods Structural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures). Results We found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed. Conclusion Our findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders

Cognitive bias in healthy participants with symptoms of depression or seasonal affective disorder

Exaggerated cognitive bias is observed in affective disorder patients, and is often probed using the Emotional Stroop (eStroop) task. Few studies of the eStroop have employed Event-Related Potentials (ERPs). Here, High-density ERPs were recorded while healthy subjects with and without sub-syndromal Depression and Seasonal Affective Disorder (SAD) performed eStroop variations containing disorder-congruent words. RTs did not reliably differentiate between groups. Emotional relative to neutral words elicited either a P1 or a new component with anterior frontal topography, the Early Anterior Positivity (EAP), maximal 200-400ms post-onset. In study 1, an EAP was elicited by depression words in subjects with and without depression, while amplitude of the Late Posterior Positivity (LPP) was greater in the depression group. In study 2, an EAP to winter-related words was observed in SAD participants during the winter, while only a P1 occurred in the summer. The EAP may index automatic processing of aversive self-relevant stimuli

The Psychophysiological Correlates of Emotion Processing in Dysphoria

The most recent extension of the cognitive vulnerability model of depression suggests that people with mild symptoms of depression (i.e. dysphoria) will show cognitive biases primarily at early information-processing stages, while people with severe symptoms of depression (i.e. clinical depression) will show cognitive biases at late information-processing stages. To date, however, few studies have empirically explored early cognitive biases in dysphoric samples. Here, I manipulated task-relevance to functionally dissociate implicit and explicit emotional processing and used scalp electroencephalograms (EEG) to look at information-processing stages in dysphoric participants. High-density EEG was recorded during the traditional task used to study cognitive biases, the emotional Stroop task (experiment 1), and an emotional word categorization task (experiment 2). Then, in my analyses, unlike previous studies, I focused particularly on early (&lt; 300 ms) frontal ERP effects that differentiated a group with dysphoria from a comparison group with few depression symptoms. I found that early ERP components over frontal scalp were significantly amplified in the dysphoric group, while common measures of late stage processing, such as the emotion-related late posterior positivity (LPP) and reaction time, did not differentiate groups, regardless of task. Next, to show that these effects could be replicated with non-word stimuli, I used emotional faces. Emotional faces are commonly used in ERP studies of attention and emotion, and are the most common stimuli used in neuroimaging studies of depression. As such, by using LORETA source analyses, I was able to tie my ERP findings into a wider literature. This work therefore lends support to the recent extension of the cognitive vulnerability model of depression, and contextualizes the previous cognitive bias results in the wider attention, emotion and depression literatures. This dissertation concludes with a suggestion that future studies carefully differentiate between-group and within-group effects, use different paradigms to dissociate “fast” vs. “slow” effects, and address the usefulness of early biases to predict the onset of depression through longitudinal studies

Fire Alarm Signal Recognition

this report, shows the spectrum analysis of the 6 signals. 4.3 Materials The signals were recorded so that they played at a maximum of 90 dBA when the CD player was at maximum volume. This volume level is not considered harmful to the hearing of the participant if the duration of the exposure is limited to 15 minutes or less and is not repeated day after day over a long period of time (WHO, 1999). The interviewer adjusted the volume of the CD player to a comfortable level for the environment they were in at the time of the study before beginning the test (this volume was usually at 4 out of a maximum volume of 10). Each participant, however, had the opportunity to adjust the volume during a 10-second period of music, prior to listening to the test signals. The signals were played on a CD Walkman (Sony Sports model D-SJ01) and both the experimenter and participant had a set of headphones to listen to the signals (the experimenter had Sony MDR-GO51 headphones). The participant listened to the signals through Sony Noise Cancelling headphones (Sony MDR-NC20) so that the ambient noise of the environment did not overly interfere with the quality of the test signals. Three experimenters collected the data. All experimenters followed a rehearsed script so that the participants experienced a similar situation with each experimenter. The experimenters recorded the participants&apos; answers on a data sheet that the participant could view at the time of the survey. 10 The answers to the perceived urgency rating were recorded on a simple 1-10 scale, although the psycho-acoustic literature lately suggests using a free-modulus magnitude estimation scale or the cross modality matching (Hellier et al., 1995). It was decided that these methods would not work well for the present study. Thes..

EEG alpha band functional connectivity reveals distinct cortical dynamics for overt and covert emotional face processing

Abstract Current knowledge regarding how the focus of our attention during face processing influences neural responses largely comes from neuroimaging studies reporting on regional brain activations. The present study was designed to add novel insights to this research by studying how attention can differentially impact the way cortical regions interact during emotional face processing. High-density electroencephalogram was recorded in a sample of fifty-two healthy participants during an emotional face processing task. The task required participants to either attend to the expressions (i.e ., overt processing) or attend to a perceptual distractor, which rendered the expressions task-irrelevant (i.e., covert processing). Functional connectivity in the alpha band was estimated in source space and modeled using graph theory to quantify whole-brain integration and segregation. Results revealed that overt processing of facial expressions is linked to reduced cortical segregation and increased cortical integration, this latter specifically for negative expressions of fear and sadness. Furthermore, we observed increased communication efficiency during overt processing of negative expressions between the core and the extended face processing systems. Overall, these findings reveal that attention makes the interaction among the nodes involved in face processing more efficient, also uncovering a connectivity signature of the prioritized processing mechanism of negative expressions, that is an increased cross-communication within the nodes of the face processing network

Spatiotemporal Dynamics of Covert Versus Overt Processing of Happy, Fearful and Sad Facial Expressions

Behavioral and electrophysiological correlates of the influence of task demands on the processing of happy, sad, and fearful expressions were investigated in a within-subjects study that compared a perceptual distraction condition with task-irrelevant faces (e.g., covert emotion task) to an emotion task-relevant categorization condition (e.g., overt emotion task). A state-of-the-art non-parametric mass univariate analysis method was used to address the limitations of previous studies. Behaviorally, participants responded faster to overtly categorized happy faces and were slower and less accurate to categorize sad and fearful faces; there were no behavioral differences in the covert task. Event-related potential (ERP) responses to the emotional expressions included the N170 (140–180 ms), which was enhanced by emotion irrespective of task, with happy and sad expressions eliciting greater amplitudes than neutral expressions. EPN (200–400 ms) amplitude was modulated by task, with greater voltages in the overt condition, and by emotion, however, there was no interaction of emotion and task. ERP activity was modulated by emotion as a function of task only at a late processing stage, which included the LPP (500–800 ms), with fearful and sad faces showing greater amplitude enhancements than happy faces. This study reveals that affective content does not necessarily require attention in the early stages of face processing, supporting recent evidence that the core and extended parts of the face processing system act in parallel, rather than serially. The role of voluntary attention starts at an intermediate stage, and fully modulates the response to emotional content in the final stage of processing

Electrophysiology of blunted emotional bias in psychopathic personality

Diminished emotional capacity is a core characteristic of psychopathic personality. We examined behavioral and electrophysiological differences in attentional bias to emotional material in 34 healthy individuals rated high or low in psychopathic traits using the short form of the Psychopathic Personality Inventory-Revised (18 high-trait, 16 low-trait). While performing an emotional Stroop task, high-trait participants displayed reduced emotional modulation of the late positive potential (LPP, 400-600\u2009ms), and early anterior positivity (EAP, 200-300\u2009ms) amplitudes. Results suggest blunted bias to affective content in psychopathic personality, characterized by diminished early capture to emotional salience (EAP) and dampened cognitive emotional processing (LPP)

An fMRI study of cognitive planning before and after symptom provocation in pediatric obsessive–compulsive disorder

Background: Pediatric obsessive–compulsive disorder (OCD) has been associated with poorer planning in laboratory, school and home settings. It is unclear whether this impairment is a standalone cognitive issue or the result of OCD symptoms. No study has examined the influence of provoked distress on planning performance and neural correlates in pediatric OCD. Methods: Before and after a symptom provocation task, youth with OCD (n = 23; 9 boys; mean age ± standard deviation 15.1 ± 2.6 years) and matched healthy controls (n = 23) completed the Tower of London task during functional MRI scanning. Results: During planning, participants with OCD recruited the left superior frontal gyrus to a greater extent than healthy controls after symptom provocation (group × time point interaction; t 44 = 5.22, p < 0.001). In a seeded, region of interest–constrained, functional connectivity analysis, we identified greater connectivity between the left superior frontal gyrus and the right middle frontal gyrus, left precuneus and left inferior parietal lobule in participants with OCD than healthy controls. We also identified greater connectivity between the right amygdala and right medial frontal gyrus in patients with OCD than healthy controls, but only before symptom provocation. Limitations: The fixed-order design of the study and the number of participants taking medication (n = 20) should be noted. Conclusion: Participants with OCD demonstrated greater amygdalar–cortical connectivity before symptom provocation, while sustaining greater recruitment and connectivity of task-related planning areas throughout the task. These results suggest that brain activity and connectivity is altered after symptom provocation, in the absence of impaired planning performance