When too much is not enough: obsessive-compulsive disorder as a pathology of stopping, rather than starting

Background

In obsessive-compulsive disorder (OCD), individuals feel compelled to repeatedly perform security-related behaviors, even though these behaviours seem excessive and unwarranted to them. The present research investigated two alternative ways of explaining such behavior: (1) a dysfunction of activation—a starting problem—in which the level of excitation in response to stimuli suggesting potential danger is abnormally strong; versus (2) a dysfunction of termination—a stopping problem—in which the satiety-like process for shutting down security-related thoughts and actions is abnormally weak.

Method

In two experiments, 70 patients with OCD (57 with washing compulsions, 13 with checking compulsions) and 72 controls were exposed to contamination cues—immersing a hand in wet diapers —and later allowed to wash their hands, first limited to 30 s and then for as long as desired. The intensity of activation of security motivation was measured objectively by change in respiratory sinus arrythmia. Subjective ratings (e.g., contamination) and behavioral measures (e.g., duration of hand washing) were also collected.

Results

Compared to controls, OCD patients with washing compulsions did not differ significantly in their levels of initial activation to the threat of contamination; however, they were significantly less able to reduce this activation by engaging in the corrective behavior of hand-washing. Further, the deactivating effect of hand-washing in OCD patients with checking compulsions was similar to that for controls, indicating that the dysfunction of termination in OCD is specific to the patient''s symptom profile.

Conclusions

These results are the first to show that OCD is characterized by a reduced ability of security-related behavior to terminate motivation evoked by potential danger, rather than a heightened initial sensitivity to potential threat. They lend support to the security-motivation theory of OCD (Szechtman & Woody, 2004) and have important implications both for research into the biological mechanisms underlying OCD and for the development of new treatment approaches.     

Self-Regulation of Brain Activity in Patients with Postherpetic Neuralgia: A Double-Blind Randomized Study Using Real-Time fMRI Neurofeedback

Background

A pilot study has shown that real-time fMRI (rtfMRI) neurofeedback could be an alternative approach for chronic pain treatment. Considering the relative small sample of patients recruited and not strictly controlled condition, it is desirable to perform a replication as well as a double-blinded randomized study with a different control condition in chronic pain patients. Here we conducted a rtfMRI neurofeedback study in a subgroup of pain patients – patients with postherpetic neuralgia (PHN) and used a different sham neurofeedback control. We explored the feasibility of self-regulation of the rostral anterior cingulate cortex (rACC) activation in patients with PHN through rtfMRI neurofeedback and regulation of pain perception.

Methods

Sixteen patients (46–71 years) with PHN were randomly allocated to a experimental group (n = 8) or a control group (n = 8). 2 patients in the control group were excluded for large head motion. The experimental group was given true feedback information from their rACC whereas the control group was given sham feedback information from their posterior cingulate cortex (PCC). All subjects were instructed to perform an imagery task to increase and decrease activation within the target region using rtfMRI neurofeedback.

Results

Online analysis showed 6/8 patients in the experimental group were able to increase and decrease the blood oxygen level dependent (BOLD) fMRI signal magnitude during intermittent feedback training. However, this modulation effect was not observed in the control group. Offline analysis showed that the percentage of BOLD signal change of the target region between the last and first training in the experimental group was significantly different from the control group’s and was also significantly different than 0. The changes of pain perception reflected by numerical rating scale (NRS) in the experimental group were significantly different from the control group. However, there existed no significant correlations between BOLD signal change and NRS change.

Conclusion

Patients with PHN could learn to voluntarily control over activation in rACC through rtfMRI neurofeedback and alter their pain perception level. The present study may provide new evidence that rtfMRI neurofeedback training may be a supplemental approach for chronic clinical pain management.     

Concordance of Epileptic Networks Associated with Epileptic Spikes Measured by High-Density EEG and Fast fMRI

Objective

The present study aims to investigate whether a newly developed fast fMRI called MREG (magnetic resonance encephalography) measures metabolic changes related to interictal epileptic discharges (IED). For this purpose BOLD changes are correlated with the IED distribution and variability.

Methods

Patients with focal epilepsy underwent EEG-MREG using a 64 channel cap. IED voltage maps were generated using 32 and 64 channels and compared regarding their correspondence to the BOLD response. The extents of IEDs (defined as number of channels with >50% of maximum IED negativity) were correlated with the extents of positive and negative BOLD responses. Differences in inter-spike variability were investigated between interictal epileptic discharges (IED) sets with and without concordant positive or negative BOLD responses.

Results

17 patients showed 32 separate IED types. In 50% of IED types the BOLD changes could be confirmed by another independent imaging method. The IED extent significantly correlated with the positive BOLD extent (p = 0.04). In 6 patients the 64-channel EEG voltage maps better reflected the positive or negative BOLD response than the 32-channel EEG; in all others no difference was seen. Inter-spike variability was significantly lower in IED sets with than without concordant positive or negative BOLD responses (with p = 0.04).

Significance

Higher density EEG and fast fMRI seem to improve the value of EEG-fMRI in epilepsy. The correlation of positive BOLD and IED extent could suggest that widespread BOLD responses reflect the IED network. Inter-spike variability influences the likelihood to find IED concordant positive or negative BOLD responses, which is why single IED analysis may be promising.     

Altered Brain Activity during Reward Anticipation in Pathological Gambling and Obsessive-Compulsive Disorder

Background

Pathological gambling (PG) and obsessive-compulsive disorder (OCD) are conceptualized as a behavioral addiction, with a dependency on repetitive gambling behavior and rewarding effects following compulsive behavior, respectively. However, no neuroimaging studies to date have examined reward circuitry during the anticipation phase of reward in PG compared with in OCD while considering repetitive gambling and compulsion as addictive behaviors.

Methods/Principal Findings

To elucidate the neural activities specific to the anticipation phase of reward, we performed event-related functional magnetic resonance imaging (fMRI) in young adults with PG and compared them with those in patients with OCD and healthy controls. Fifteen male patients with PG, 13 patients with OCD, and 15 healthy controls, group-matched for age, gender, and IQ, participated in a monetary incentive delay task during fMRI scanning. Neural activation in the ventromedial caudate nucleus during anticipation of both gain and loss decreased in patients with PG compared with that in patients with OCD and healthy controls. Additionally, reduced activation in the anterior insula during anticipation of loss was observed in patients with PG compared with that in patients with OCD which was intermediate between that in OCD and healthy controls (healthy controls < PG < OCD), and a significant positive correlation between activity in the anterior insula and South Oaks Gambling Screen score was found in patients with PG.

Conclusions

Decreased neural activity in the ventromedial caudate nucleus during anticipation may be a specific neurobiological feature for the pathophysiology of PG, distinguishing it from OCD and healthy controls. Correlation of anterior insular activity during loss anticipation with PG symptoms suggests that patients with PG fit the features of OCD associated with harm avoidance as PG symptoms deteriorate. Our findings have identified functional disparities and similarities between patients with PG and OCD related to the neural responses associated with reward anticipation.     

Abnormalities of white matter microstructure in unmedicated obsessive-compulsive disorder and changes after medication

Background

Abnormalities of myelin integrity have been reported in obsessive-compulsive disorder (OCD) using multi-parameter maps of diffusion tensor imaging (DTI). However, it was still unknown to what degree these abnormalities might be affected by pharmacological treatment.

Objective

To investigate whether the abnormalities of white matter microstructure including myelin integrity exist in OCD and whether they are affected by medication.

Methodology and Principal Findings

Parameter maps of DTI, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), were acquired from 27 unmedicated OCD patients (including 13 drug-naïve individuals) and 23 healthy controls. Voxel-based analysis was then performed to detect regions with significant group difference. We compared the DTI-derived parameters of 15 patients before and after 12-week Selective Serotonin Reuptake Inhibitor (SSRI) therapies. Significant differences of DTI-derived parameters were observed between OCD and healthy groups in multiple structures, mainly within the fronto-striato-thalamo-cortical loop. An increased RD in combination with no change in AD among OCD patients was found in the left medial superior frontal gyrus, temporo-parietal lobe, occipital lobe, striatum, insula and right midbrain. There was no statistical difference in DTI-derived parameters between drug-naive and previously medicated OCD patients. After being medicated, OCD patients showed a reduction in RD of the left striatum and right midbrain, and in MD of the right midbrain.

Conclusion

Our preliminary findings suggest that abnormalities of white matter microstructure, particularly in terms of myelin integrity, are primari ly located within the fronto-striato-thalamo-cortical circuit of individuals with OCD. Some abnormalities may be partly reversed by SSRI treatment.     

COMT and MAO-A Polymorphisms and Obsessive-Compulsive Disorder: A Family-Based Association Study

Objective

Obsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design.

Methods

Transmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed.

Results

OCD, broad and narrow phenotypes,were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A.

Conclusions

The findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.     

Neural Correlates of Empathy with Pain Show Habituation Effects. An fMRI Study

Background

Neuroimaging studies have demonstrated that the actual experience of pain and the perception of another person in pain share common neural substrates, including the bilateral anterior insular cortex and the anterior midcingulate cortex. As many fMRI studies include the exposure of participants to repeated, similar stimuli, we examined whether empathic neural responses were affected by habituation and whether the participants'' prior pain experience influenced these habituation effects.

Method

In 128 trials (four runs), 62 participants (31 women, 23.0 ± 4.2 years) were shown pictures of hands exposed to painful pressure (pain pictures) and unexposed (neutral pictures). After each trial, the participants rated the pain of the model. Prior to the experiment, participants were either exposed to the same pain stimulus (pain exposure group) or not (touch exposure group). In order to assess possible habituation effects, linear changes in the strength of the BOLD response to the pain pictures (relative to the neutral pictures) and in the ratings of the model’s pain were evaluated across the four runs.

Results

Although the ratings of the model’s pain remained constant over time, we found neural habituation in the bilateral anterior/midinsular cortex, the posterior midcingulate extending to dorsal posterior cingulate cortex, the supplementary motor area, the cerebellum, the right inferior parietal lobule, and the left superior frontal gyrus, stretching to the pregenual anterior cingulate cortex. The participant’s prior pain experience did neither affect their ratings of the model’s pain nor their maintenance of BOLD activity in areas associated with empathy. Interestingly, participants with high trait personal distress and fantasy tended to show less habituation in the anterior insula.

Conclusion

Neural structures showed a decrease of the BOLD signal, indicating habituation over the course of 45 minutes. This can be interpreted as a neuronal mechanism responding to the repeated exposure to pain depictions, which may be regarded as functional in a range of contexts.     

Cortical Thickness in Dementia with Lewy Bodies and Alzheimer's Disease: A Comparison of Prodromal and Dementia Stages

Objectives

To assess and compare cortical thickness (CTh) of patients with prodromal Dementia with Lewy bodies (pro-DLB), prodromal Alzheimer''s disease (pro-AD), DLB dementia (DLB-d), AD dementia (AD-d) and normal ageing.

Methods

Study participants(28 pro-DLB, 27 pro-AD, 31 DLB-d, 54 AD-d and 33 elderly controls) underwent 3Tesla T1 3D MRI and detailed clinical and cognitive assessments. We used FreeSurfer analysis package to measure CTh and investigate patterns of cortical thinning across groups.

Results

Comparison of CTh between pro-DLB and pro-AD (p<0.05, FDR corrected) showed more right anterior insula thinning in pro-DLB, and more bilateral parietal lobe and left parahippocampal gyri thinning in pro-AD. Comparison of prodromal patients to healthy elderly controls showed the involvement of the same regions. In DLB-d (p<0.05, FDR corrected) cortical thinning was found predominantly in the right temporo-parietal junction, and insula, cingulate, orbitofrontal and lateral occipital cortices. In AD-d(p<0.05, FDR corrected),the most significant areas affected included the entorhinal cortices, parahippocampal gyri and parietal lobes. The comparison of AD-d and DLB-d demonstrated more CTh in AD-d in the left entorhinal cortex (p<0.05, FDR corrected).

Conclusion

Cortical thickness is a sensitive measure for characterising patterns of grey matter atrophy in early stages of DLB distinct from AD. Right anterior insula involvement may be a key region at the prodromal stage of DLB and needs further investigation.     

Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI

Background

Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging.

Methods

A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity.

Results

Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores.

Conclusion

Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as potential biomarkers for assessment of neuronal damage and the prediction of clinical outcomes in acute SCI.     

Factors Associated with Blood Culture Contamination in the Emergency Department: Critical Illness,End-Stage Renal Disease,and Old Age

Background

Blood culture contamination in emergency departments (ED) that experience a high volume of patients has negative impacts on optimal patient care. It is therefore important to identify risk factors associated with blood culture contamination in EDs.

Methodology/Principal Findings

A prospectively observational study in a university-affiliated hospital were conducted between August 2011 and December 2012. Positive monomicrobial and negative blood cultures drawn from adult patients in the ED were analyzed to evaluate the possible risk factors for contamination. A total of 1,148 positive monomicrobial cases, 391 contamination cases, and 13,689 cases of negative blood culture were identified. Compared to patients with negative blood cultures, patients in triage levels 1 and 2 (Incidence Rate Ratio, IRR = 2.24), patients with end-stage renal disease (ESRD) (IRR = 2.05), and older patients (IRR: 1.02 per year) were more likely to be associated with ED blood culture contamination.

Conclusions/Significance

Critical patients (triage levels 1 and 2), ESRD patients, and older patients were more commonly associated with blood culture contamination in the ED. Further studies to evaluate whether the characteristics of skin commensals contribute to blood culture contamination is warranted, especially in hospitals populated with high-risk patients.     

Increased Grey Matter Associated with Long-Term Sahaja Yoga Meditation: A Voxel-Based Morphometry Study

Objectives

To investigate regional differences in grey matter volume associated with the practice of Sahaja Yoga Meditation.

Design

Twenty three experienced practitioners of Sahaja Yoga Meditation and twenty three non-meditators matched on age, gender and education level, were scanned using structural Magnetic Resonance Imaging and their grey matter volume were compared using Voxel-Based Morphometry.

Results

Grey matter volume was larger in meditators relative to non-meditators across the whole brain. In addition, grey matter volume was larger in several predominantly right hemispheric regions: in insula, ventromedial orbitofrontal cortex, inferior temporal and parietal cortices as well as in left ventrolateral prefrontal cortex and left insula. No areas with larger grey matter volume were found in non-meditators relative to meditators.

Conclusions

The study shows that long-term practice of Sahaja Yoga Meditation is associated with larger grey matter volume overall, and with regional enlargement in several right hemispheric cortical and subcortical brain regions that are associated with sustained attention, self-control, compassion and interoceptive perception. The increased grey matter volume in these attention and self-control mediating regions suggests use-dependent enlargement with regular practice of this meditation.     

Calcitonin Gene-Related Peptide Modulates Heat Nociception in the Human Brain - An fMRI Study in Healthy Volunteers

Background

Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded blood-oxygenation-level-dependent (BOLD) signals in the brain by functional MRI after infusion of CGRP in a double-blind placebo-controlled crossover study of 27 healthy volunteers. BOLD-signals were recorded in response to noxious heat stimuli in the V1-area of the trigeminal nerve. In addition, we measured BOLD-signals after injection of sumatriptan (5-HT_1B/1D antagonist).

Results

Brain activation to noxious heat stimuli following CGRP infusion compared to baseline resulted in increased BOLD-signal in insula and brainstem, and decreased BOLD-signal in the caudate nuclei, thalamus and cingulate cortex. Sumatriptan injection reversed these changes.

Conclusion

The changes in BOLD-signals in the brain after CGRP infusion suggests that systemic CGRP modulates nociceptive transmission in the trigeminal pain pathways in response to noxious heat stimuli.     

Obsessive-Compulsive Disorder and Autism Spectrum Disorders: Longitudinal and Offspring Risk

Background

Despite substantial similarities and overlaps in the pathophysiology of obsessive-compulsive disorders (OCD) and autism spectrum disorders, little is known about the clinical and etiologic cohesion of these two disorders. We therefore aimed to determine the patterns of comorbidity, longitudinal risks, and shared familial risks between these disorders.

Methods

In a prospective study design we explored the effect of a prior diagnosis of OCD in patients and parents on the susceptibility to autism spectrum disorders and vice versa. Analyses were adjusted for sex, age, calendar year, parental age and place at residence at time of birth. As measures of relative risk incidence rate ratios (IRR) and accompanying 95% confidence intervals (CIs) were employed.

Results

The risk of a comorbid diagnosis of OCD in individuals with autism spectrum disorder and aggregation of autism spectrum disorders in offspring of parents with OCD were increased. Individuals first diagnosed with autism spectrum disorders had a 2-fold higher risk of a later diagnosis of OCD (IRR = 2.18, 95% CI = 1.91–2.48), whereas individuals diagnosed with OCD displayed a nearly 4-fold higher risk to be diagnosed with autism spectrum disorders (IRR = 3.91, 95% CI = 3.46–4.40) later in life. The observed associations were somewhat stronger for less severe types of autism spectrum disorders without a comorbid diagnosis of mental disabilities.

Conclusions

The high comorbidity, sequential risk, and shared familial risks between OCD and autism spectrum disorders are suggestive of partially shared etiological mechanisms. The results have implications for current gene-searching efforts and for clinical practice.     

Facial Emotion Recognition in Parkinson's Disease: An fMRI Investigation

Background

Findings of behavioral studies on facial emotion recognition in Parkinson’s disease (PD) are very heterogeneous. Therefore, the present investigation additionally used functional magnetic resonance imaging (fMRI) in order to compare brain activation during emotion perception between PD patients and healthy controls.

Methods and Findings

We included 17 nonmedicated, nondemented PD patients suffering from mild to moderate symptoms and 22 healthy controls. The participants were shown pictures of facial expressions depicting disgust, fear, sadness, and anger and they answered scales for the assessment of affective traits. The patients did not report lowered intensities for the displayed target emotions, and showed a comparable rating accuracy as the control participants. The questionnaire scores did not differ between patients and controls. The fMRI data showed similar activation in both groups except for a generally stronger recruitment of somatosensory regions in the patients.

Conclusions

Since somatosensory cortices are involved in the simulation of an observed emotion, which constitutes an important mechanism for emotion recognition, future studies should focus on activation changes within this region during the course of disease.     

Combinational Therapy Enhances the Effects of Anti-IGF-1R mAb Figitumumab to Target Small Cell Lung Cancer

Background

Small cell lung cancer (SCLC) is a recalcitrant malignancy with distinct biologic properties. Antibody targeting therapy has been actively investigated as a new drug modality.

Methods

We tested the expression of IGF-1R and calculated the survival in 61 SCLC patients. We also evaluated the anti-tumor effects of anti-IGF-1R monoclonal antibody Figitumumab (CP) on SCLC, and tried two drug combinations to improve CP therapy.

Results

Our clinical data suggested that high IGF-1R expression was correlated with low SCLC patient survival. We then demonstrated the effect of CP was likely through IGF-1R blockage and down-regulation without IGF-1R auto-phosphorylation and PI3K/AKT activation. However, we observed elevated MEK/ERK activation upon CP treatment in SCLC cells, and this MEK/ERK activation was enhanced by ß-arrestin1 knockdown while attenuated by ß-arrestin2 knockdown. We found both MEK/ERK inhibitor and metformin could enhance CP treatment in SCLC cells. We further illustrated the additive effect of metformin was likely through promoting further IGF-1R down-regulation.

Conclusion

Our results highlighted the potential of anti-IGF-1R therapy and the adjuvant therapy strategy with either MEK/ERK inhibitor or metformin to target SCLC, warranting further studies.     

Infarction Distribution Pattern in Acute Stroke May Predict the Extent of Leptomeningeal Collaterals

Objective

The aim of this study was to evaluate whether the distribution pattern of early ischemic changes in the initial MRI allows a practical method for estimating leptomeningeal collateralization in acute ischemic stroke (AIS).

Methods

Seventy-four patients with AIS underwent MRI followed by conventional angiogram and mechanical thrombectomy. Diffusion restriction in Diffusion weighted imaging (DWI) and correlated T2-hyperintensity of the infarct were retrospectively analyzed and subdivided in accordance with Alberta Stroke Program Early CT score (ASPECTS). Patients were angiographically graded in collateralization groups according to the method of Higashida, and dichotomized in 2 groups: 29 subjects with collateralization grade 3 or 4 (well-collateralized group) and 45 subjects with grade 1 or 2 (poorly-collateralized group). Individual ASPECTS areas were compared among the groups.

Results

Means for overall DWI-ASPECTS were 6.34 vs. 4.51 (well vs. poorly collateralized groups respectively), and for T2-ASPECTS 9.34 vs 8.96. A significant difference between groups was found for DWI-ASPECTS (p<0.001), but not for T2-ASPECTS (p = 0.088). Regarding the individual areas, only insula, M1-M4 and M6 showed significantly fewer infarctions in the well-collateralized group (p-values <0.001 to 0.015). 89% of patients in the well-collateralized group showed 0–2 infarctions in these six areas (44.8% with 0 infarctions), while 59.9% patients of the poor-collateralized group showed 3–6 infarctions.

Conclusion

Patients with poor leptomeningeal collateralization show more infarcts on the initial MRI, particularly in the ASPECTS areas M1 to M4, M6 and insula. Therefore DWI abnormalities in these areas may be a surrogate marker for poor leptomeningeal collaterals and may be useful for estimation of the collateral status in routine clinical evaluation.     

Altered Hemodynamic Activity in Conduct Disorder: A Resting-State fMRI Investigation

Background

Youth with conduct disorder (CD) not only inflict serious physical and psychological harm on others, but are also at greatly increased risk of sustaining injuries, developing depression or substance abuse, and engaging in criminal behaviors. The underlying neurobiological basis of CD remains unclear.

Objective

The present study investigated whether participants with CD have altered hemodynamic activity under resting-state conditions.

Methods

Eighteen medication-naïve boys with CD and 18 age- and sex- matched typically developing (TD) controls underwent functional magnetic resonance imaging (MRI) scans in the resting state. The amplitude of low-frequency fluctuations (ALFF) was measured and compared between the CD and TD groups.

Results

Compared with the TD participants, the CD participants showed lower ALFF in the bilateral amygdala/parahippocampus, right lingual gyrus, left cuneus and right insula. Higher ALFF was observed in the right fusiform gyrus and right thalamus in the CD participants compared to the TD group.

Conclusions

Youth with CD displayed widespread functional abnormalities in emotion-related and visual cortical regions in the resting state. These results suggest that deficits in the intrinsic activity of resting state networks may contribute to the etiology of CD.     

Pain Processing after Social Exclusion and Its Relation to Rejection Sensitivity in Borderline Personality Disorder

Objective

There is a general agreement that physical pain serves as an alarm signal for the prevention of and reaction to physical harm. It has recently been hypothesized that “social pain,” as induced by social rejection or abandonment, may rely on comparable, phylogenetically old brain structures. As plausible as this theory may sound, scientific evidence for this idea is sparse. This study therefore attempts to link both types of pain directly. We studied patients with borderline personality disorder (BPD) because BPD is characterized by opposing alterations in physical and social pain; hyposensitivity to physical pain is associated with hypersensitivity to social pain, as indicated by an enhanced rejection sensitivity.

Method

Twenty unmedicated female BPD patients and 20 healthy participants (HC, matched for age and education) played a virtual ball-tossing game (cyberball), with the conditions for exclusion, inclusion, and a control condition with predefined game rules. Each cyberball block was followed by a temperature stimulus (with a subjective pain intensity of 60% in half the cases). The cerebral responses were measured by functional magnetic resonance imaging. The Adult Rejection Sensitivity Questionnaire was used to assess rejection sensitivity.

Results

Higher temperature heat stimuli had to be applied to BPD patients relative to HCs to reach a comparable subjective experience of painfulness in both groups, which suggested a general hyposensitivity to pain in BPD patients. Social exclusion led to a subjectively reported hypersensitivity to physical pain in both groups that was accompanied by an enhanced activation in the anterior insula and the thalamus. In BPD, physical pain processing after exclusion was additionally linked to enhanced posterior insula activation. After inclusion, BPD patients showed reduced amygdala activation during pain in comparison with HC. In BPD patients, higher rejection sensitivity was associated with lower activation differences during pain processing following social exclusion and inclusion in the insula and in the amygdala.

Discussion

Despite the similar behavioral effects in both groups, BPD patients differed from HC in their neural processing of physical pain depending on the preceding social situation. Rejection sensitivity further modulated the impact of social exclusion on neural pain processing in BPD, but not in healthy controls.     

The acceptability of Internet-based treatment and characteristics of an adult sample with obsessive compulsive disorder: an Internet survey

Background

Obsessive-compulsive disorder (OCD) is a disabling anxiety disorder, but most individuals delay seeking treatment. Internet-based cognitive behavioural therapy (iCBT) is an innovative service delivery method that may help to improve access to care, but the acceptability to consumers of such programs has not yet been established.

Methodology

People with symptoms of OCD were invited to complete an online survey enquiring about demographic characteristics, symptom severity, and acceptability of Internet-based treatment. Demographic and symptom severity data were compared with people with OCD identified in a national epidemiological survey and with a sample of patients with OCD from a specialist outpatient anxiety clinic.

Participants

129 volunteers to an online Internet survey, 135 patients at a specialist anxiety disorders outpatient clinic, and 297 cases identified in a national epidemiological survey.

Main Measures

Demographic characteristics, and severity of symptoms as measured by the Kessler 10-Item scale, the 12-item World Health Organisation Disability Assessment Schedule - Second Edition and the Yale Brown Obsessive Compulsive Scale - Self Report Version.

Principal Findings

The Internet sample was similar demographically but reported more severe symptoms than the comparison groups, although had similar severity of symptoms of OCD compared with other clinical samples reported in the literature. Participants reported Internet-based treatment for OCD would be highly acceptable.

Conclusions

Internet-based treatment may reduce barriers to accessing treatment to people with OCD. Individuals in this study were similar demographically to other samples and had similar severity of symptoms as those identified in other clinical samples, suggesting that Internet-based treatment using techniques employed in face-to-face treatment may be effective in this group. Internet-based treatments for OCD need to be developed and evaluated.     

Reduced Functional Connectivity of Default Mode and Set-Maintenance Networks in Ornithine Transcarbamylase Deficiency

Background and Purpose

Ornithine transcarbamylase deficiency (OTCD) is an X-chromosome linked urea cycle disorder (UCD) that causes hyperammonemic episodes leading to white matter injury and impairments in executive functioning, working memory, and motor planning. This study aims to investigate differences in functional connectivity of two resting-state networks—default mode and set-maintenance—between OTCD patients and healthy controls.

Methods

Sixteen patients with partial OTCD and twenty-two control participants underwent a resting-state scan using 3T fMRI. Combining independent component analysis (ICA) and region-of-interest (ROI) analyses, we identified the nodes that comprised each network in each group, and assessed internodal connectivity.

Results

Group comparisons revealed reduced functional connectivity in the default mode network (DMN) of OTCD patients, particularly between the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) node and bilateral inferior parietal lobule (IPL), as well as between the ACC/mPFC node and the posterior cingulate cortex (PCC) node. Patients also showed reduced connectivity in the set-maintenance network, especially between right anterior insula/frontal operculum (aI/fO) node and bilateral superior frontal gyrus (SFG), as well as between the right aI/fO and ACC and between the ACC and right SFG.

Conclusion

Internodal functional connectivity in the DMN and set-maintenance network is reduced in patients with partial OTCD compared to controls, most likely due to hyperammonemia-related white matter damage. Because several of the affected areas are involved in executive functioning, it is postulated that this reduced connectivity is an underlying cause of the deficits OTCD patients display in this cognitive domain.