Development of Posterior Medial Frontal Cortex Function in Pediatric Obsessive-Compulsive Disorder.
ABSTRACT: OBJECTIVE:Abnormal engagement of the posterior medial frontal cortex (pMFC) occurs during performance monitoring in obsessive-compulsive disorder (OCD), including in pediatric patients. Yet, the development of pMFC function in OCD-affected youth remains poorly understood. METHOD:A total of 69 patients with pediatric OCD and 72 healthy controls (HC), 8 to 19 years of age, were scanned during the Multisource Interference Task (MSIT). The effects of group, age, performance, and interactions on pMFC response to errors and interference were tested in the region of interest [ROI]) and whole-brain analyses. Secondary analyses considered bilateral anterior insula/frontal operculum (aI/fO), given the contribution of these regions with pMFC to a cingulo-opercular network (CON) for task control (e.g., error and interference processing). RESULTS:Error-related pMFC activity was greater for OCD patients than for HC, increased with age in OCD patients, but decreased with age in HC. Greater pMFC activation associated with better performance in HC but not OCD patients. In the patients, greater pMFC activation to errors was associated with lower OCD severity. Altered error-related activation and performance associations were also observed in the right aI/fO in OCD patients, whereas the left aI/fO response to interference was associated with lower OCD severity. CONCLUSION:Atypical increase in error-related pMFC activation with age in pediatric OCD suggests altered development of pMFC function during the early course of illness. Greater pMFC activation with better performance in HC, and with age and lower symptom severity in OCD patients, suggests an adaptive function of heightened pMFC response to errors that could be further enhanced (e.g., via cognitive training) to improve outcomes in OCD from the early course of illness.
Project description:To characterize the development of neural substrate for interference processing and task control, this study examined both linear and non-linear effects of age on activation and connectivity during an interference task designed to engage the posterior medial frontal cortex (pMFC). Seventy-two youth, ages 8-19years, performed the Multi-Source Interference Task (MSIT) during functional magnetic resonance imaging (fMRI). With increasing age, overall performance across high-interference incongruent and low-interference congruent trials became faster and more accurate. Effects of age on activation to interference- (incongruent versus congruent conditions), error- (errors versus correct trials during the incongruent condition) and overall task-processing (incongruent plus congruent conditions, relative to implicit baseline) were tested in whole-brain voxel-wise analyses. Age differentially impacted activation to overall task processing in discrete sub-regions of the pMFC: activation in the pre-supplementary motor area (pre-SMA) decreased with age, whereas activation in the dorsal anterior cingulate cortex (dACC) followed a non-linear (i.e., U-shaped) pattern in relation to age. In addition, connectivity of pre-SMA with anterior insula/frontal operculum (AI/FO) increased with age. These findings suggest differential development of pre-SMA and dACC sub-regions within the pMFC. Moreover, as children age, decreases in pre-SMA activation may couple with increases in pre-SMA-AI/FO connectivity to support gains in processing speed in response to demands for task control.
Project description:Patients with obsessive-compulsive disorder (OCD) show abnormal functioning in ventral frontal brain regions involved in emotional/motivational processes, including anterior insula/frontal operculum (aI/fO) and ventromedial frontal cortex (VMPFC). While OCD has been associated with an increased neural response to errors, the influence of motivational factors on this effect remains poorly understood.To investigate the contribution of motivational factors to error processing in OCD and to examine functional connectivity between regions involved in the error response, functional magnetic resonance imaging data were measured in 39 OCD patients (20 unmedicated, 19 medicated) and 38 control subjects (20 unmedicated, 18 medicated) during an error-eliciting interference task where motivational context was varied using monetary incentives (null, loss, and gain).Across all errors, OCD patients showed reduced deactivation of VMPFC and greater activation in left aI/FO compared with control subjects. For errors specifically resulting in a loss, patients further hyperactivated VMPFC, as well as right aI/FO. Independent of activity associated with task events, OCD patients showed greater functional connectivity between VMPFC and regions of bilateral aI/FO and right thalamus.Obsessive-compulsive disorder patients show greater activation in neural regions associated with emotion and valuation when making errors, which could be related to altered intrinsic functional connectivity between brain networks. These results highlight the importance of emotional/motivational responses to mistakes in OCD and point to the need for further study of network interactions in the disorder.
Project description:Pediatric patients with obsessive-compulsive disorder (OCD) show an increased electrophysiological response to errors that is thought to be localized to the posterior medial prefrontal cortex (pMFC). However, the relation of this response, the error-related negativity (ERN), to underlying brain structures remains unknown. In an examination of 20 pediatric OCD patients and 20 healthy youth, we found that more negative ERN amplitude was correlated with lower gray matter (GM) density in pMFC and orbital frontal cortex. The association of the ERN with pMFC gray matter volume was driven by the patient group. In addition, a group difference in the association of ERN with gray matter in right insula was observed, showing an association of these measures in healthy youth (more negative ERN amplitude was associated with lower GM density in insula), but not in patients. These findings provide preliminary evidence linking gray matter volumes in an extended network for error processing to the ERN, and suggest that structural alterations in this network may underlie exaggeration of the ERN in pediatric OCD.
Project description:Obsessive-compulsive disorder (OCD) is associated with an abnormally large error-related negativity (ERN), an electrophysiological measure of error monitoring in response to performance errors, but it is unclear if hoarding disorder (HD) also shows this abnormality. This study aimed to determine whether the neurophysiological mechanisms underlying error monitoring are similarly compromised in HD and OCD.We used a visual flanker task to assess ERN in response to performance errors in 14 individuals with HD, 27 with OCD, 10 with HD+OCD, and 45 healthy controls (HC). Age-corrected performance and ERN amplitudes were examined using analyses of variance and planned pairwise group comparisons.A main effect of hoarding on ERN (p = 0.031) was observed, indicating ERN amplitudes were attenuated in HD relative to non-HD subjects. A group × age interaction effect on ERN was also evident. In HD-positive subjects, ERN amplitude deficits were significantly greater in younger individuals (r = -0.479, p = 0.018), whereas there were no significant ERN changes with increasing age in OCD and HC participants.The reduced ERN in HD relative to OCD and HC provides evidence that HD is neurobiologically distinct from OCD, and suggests that deficient error monitoring may be a core pathophysiological feature of HD. This effect was particularly prominent in younger HD participants, further suggesting that deficient error monitoring manifests most strongly early in the illness course and/or in individuals with a relatively early illness onset.
Project description:BACKGROUND:Impaired cognitive flexibility has been implicated in the genetic basis of obsessive-compulsive disorder (OCD). Recent endophenotype studies of OCD showed neural inefficiency in the cognitive control network and interference by the limbic network of the cognitive control network. Exploring the relationship between the functional brain network and impaired cognitive flexibility may provide novel information about the neurobiological basis of OCD. METHODS:We obtained resting-state functional magnetic resonance imaging (rsfMRI) scans and measured the cognitive flexibility of 37 medication-free OCD patients and 40 healthy control (HC) participants using the Wisconsin Card Sorting Test (WCST). We explored the difference between OCD and HC groups in the functional brain network related to impaired cognitive flexibility from the amygdala and dorsal striatal regions of interest (ROIs) by using a seed-based approach. RESULTS:Significant differences between the OCD and HC groups were identified in the resting state functional network from the dorsal caudate. Increased functional connectivity from the dorsal caudate to the dorsal anterior cingulate cortex (dACC) and anterior insula (AI) was associated with poorer cognitive flexibility in the OCD group, but better cognitive flexibility in the HC group. CONCLUSIONS:These results provide evidence that the impaired cognitive flexibility of OCD may be associated with dysfunctions of the brain network from the dorsal caudate (DC) to important nodes of the salience network. Our results extend the neuropsychological model of OCD by showing intrinsically different associations between OCD and HC in functional network and cognitive flexibility.
Project description:Abnormalities of cognitive control functions, such as conflict and error monitoring, have been theorized to underlie obsessive-compulsive symptoms but only recently have been considered a potentially relevant psychological construct for understanding other forms of anxiety. The authors sought to determine whether these cognitive control processes elicit the same abnormalities of brain function in patients with pediatric obsessive-compulsive disorder (OCD) as in those with non-OCD anxiety disorders.Functional magnetic resonance imaging of the Multisource Interference Task was used to measure conflict- and error-related activations in youth (8-18 years) with OCD (n = 21) and non-OCD anxiety disorders (generalized anxiety disorder, social phobia, separation anxiety disorder; n = 23) compared with age-matched healthy controls (n = 25).There were no differences in performance (accuracy, response times) among groups. However, a significant effect of group was observed in the dorsolateral prefrontal cortex (dlPFC) during error processing, driven by decreased activation in patients with OCD and those with non-OCD anxiety compared with healthy youth. Between patient groups, there was no difference in error-related dlPFC activation.Hypoactive dlPFC response to errors occurs in pediatric patients with OCD and those with non-OCD anxiety. These findings suggest that insufficient error-related engagement of the dlPFC associates with anxiety across traditional diagnostic boundaries and appears during the early stages of illness.
Project description:Few studies have explored the neurobiological basis of insight level in obsessive-compulsive disorder (OCD), though the salience network (SN) has been implicated in insight deficits in schizophrenia. This study was then designed to investigate whether resting-state (rs) functional connectivity (FC) of SN was associated with insight level in OCD patients. We analyzed rs-functional magnetic resonance imaging (fMRI) data from 21 OCD patients with good insight (OCD-GI), 19 OCD patients with poor insight (OCD-PI), and 24 healthy controls (HCs). Seed-based whole-brain FC and ROI (region of interest)-wise connectivity analyses were performed with seeds/ROIs in the bilateral anterior insula (AI) and dorsal anterior cingulate cortex (dACC). The right AI-right medial orbital frontal cortex (mOFC) connectivity was found to be uniquely decreased in the OCD-PI group, and the value of this aberrant connectivity correlated with insight level in OCD patients. In addition, we found that the OCD-GI group had significantly increased right AI-left dACC connectivity within the SN, relative to HCs (overall trend for groups: OCD-GI > OCD-PI > HC). Our findings suggest that abnormal right AI-right mOFC FC may mediate insight deficits in OCD, perhaps due to impaired encoding and integration of self-evaluative information about OCD-related beliefs and behaviors. Our findings indicate a SN connectivity dissociation between OCD-GI and OCD-PI patients and support the notion of considering OCD-GI and OCD-PI as two distinct disorder subtypes.
Project description:The anterior insula has been hypothesized to provide a link between attention-related problem solving and salience systems during the coordination and evaluation of task performance. Here, we test the hypothesis that the anterior insula/medial frontal operculum (aI/fO) provides linkage across systems supporting task demands and attention systems by examining the patterns of functional connectivity during word recognition and spatial attention functional imaging tasks. A shared set of frontal regions (right aI/fO, right dorsolateral prefrontal cortex, bilateral anterior cingulate) were engaged, regardless of perceptual domain (auditory or visual) or mode of response (word production or button press). We present novel evidence that: (1) the right aI/fO is functionally connected with other frontal regions implicated in executive function and not just brain regions responsive to stimulus salience; and (2) that the aI/fO, but not the ACC, exhibits significantly correlated activity with other brain regions specifically engaged by tasks with varying perceptual and behavioral demands. These results support the hypothesis that the right aI/fO aids in the coordination and evaluation of task performance across behavioral tasks with varying perceptual and response demands.
Project description:BACKGROUND:Customized foot orthoses (FOs) are designed based on foot posture and function, while the interaction between these metrics and FO deformation remains unknown due to technical problems. Our aim was to predict FO deformation under dynamic loading using an artificial intelligence (AI) approach, and to report the deformation of two FOs of different stiffness during walking. METHODS:Each FO was fixed on a plate, and six triad reflective markers were fitted on its contour, and 55 markers on its plantar surface. Manual loadings with known magnitude and application point were applied to deform "sport" and "regular" (stiffer) FOs in all regions (training session). Then, 13 healthy male subjects walked with the same FOs inside shoes, where the triad markers were visible by means of shoe holes (walking session). The marker trajectories were recorded using optoelectronic system. A neural network was trained to find the dependency between the orientation of triads on FO contour and the position of markers on its plantar surface. After tuning hyperparameters and evaluating the performance of the model, marker positions on FOs surfaces were predicted during walking for each subject. Statistical parametric mapping was used to compare the pattern of deformation between two FOs. RESULTS:Overall, the model showed an average error of <0.6 mm for predicting the marker positions on both FOs. The training setup was appropriate to simulate the range of triads' displacement and the peak loading on FOs during walking. Sport FO showed different pattern and significantly higher range of deformation during walking compared to regular FO. CONCLUSION:Our technique enables an indirect and accurate estimation of FO surface deformation during walking. The AI model was capable to make a distinction between two FOs with different stiffness and between subjects. This innovative approach can help to optimally customize the FO design.
Project description:Many voxel-based morphometry (VBM) studies have found abnormalities in gray matter density (GMD) in obsessive-compulsive disorder (OCD). Here, we performed a quantitative meta-analysis of VBM studies contrasting OCD patients with healthy controls (HC). A literature search identified 10 articles that included 343 OCD patients and 318 HC. Anatomic likelihood estimation meta-analyses were performed to assess GMD changes in OCD patients relative to HC. GMD was smaller in parieto-frontal cortical regions, including the supramarginal gyrus, the dorsolateral prefrontal cortex, and the orbitofrontal cortex, and greater in the basal ganglia (putamen) and the anterior prefrontal cortex in OCD patients relative to HC. No significant differences were found between children and adults. Our findings indicate differences in GMD in parieto-frontal areas and the basal ganglia between OCD patients and HC. We conclude that structural abnormalities within the prefrontal-basal ganglia network are involved in OCD pathophysiology.