Neural bases of the clinical and neurocognitive differences between earlyand late-onset obsessive­compulsive disorder

Background: Using biological evidence to define subtypes within the heterogeneous population with obsessive­compulsive disorder (OCD) is important for improving treatment response. Based on age at onset, OCD can be clustered into 2 groups, each of which is more homogeneous with respect to clinical and cognitive phenotype. However, the neural bases for these phenotypic differences need to be established to construct evidence-based homogeneous groups. Methods: We compared brain volumes, clinical symptoms, and neurocognitive function for 49 people with early-onset OCD and 52 with late-onset OCD (participants in both groups were unmedicated or drug-naïve), and 103 healthy controls. We performed regression analyses to examine group × volume interaction effects on clinical outcomes or neurocognitive function in people with OCD. Results: We observed larger volumes in the precentral, orbitofrontal, middle frontal, and middle temporal gyri in people with early-onset OCD compared to those with late-onset OCD. Poorer visuospatial construction in early-onset OCD was correlated with a larger left middle frontal gyrus volume. Impaired visuospatial memory in people with early-onset OCD and cognitive inflexibility in people with late-onset OCD were correlated with increased and decreased volume in the left middle frontal gyrus, respectively. We found group × volume interactions for obsessive­compulsive symptom scores in the left middle temporal gyrus of people with OCD. Limitations: Although we divided the subtypes using the commonly adopted criterion of age at onset, this criterion is still somewhat controversial. Conclusion: We provided the neural bases for clinical and neurocognitive differences to demonstrate that biological evidence underlies the distinctions between early- and late-onset OCD. This study suggests that different treatment options should be considered for the OCD subtypes, because their neurobiology differs and is related to distinct phenotypic profiles.

The effects of four days of intensive mindfulness meditation training (Templestay program) on resilience to stress: a randomized controlled trial.

The interest in mindfulness meditation interventions has surged due to their beneficial effects in fostering resilience and reducing stress in both clinical and non-clinical populations. However, the relaxation benefits that may occur while practicing mindfulness meditation and long-term benefits of these interventions remain unclear. Fifty-one participants were recruited and randomized into the experimental and control groups, which underwent 4 days of Intensive Meditation (Templestay program, n = 33) and Relaxation (Control, n = 18), respectively. The self-report measures of Cognitive and Affective Mindfulness Scale-Revised (CAMS) and the modified Korean version of the Resilience Quotient Test (RQT) were administered pre-, post- and 3 months after the intervention to measure participants' levels of mindfulness and resilience. Participants in both the Templestay program and Control groups showed significant increases in their scores on CAMS and RQT after completing the program. During the 3-month follow-up, a significant interaction effect of the intervention method and time was revealed for the individuals' CAMS and RQT scores. Our findings support the hypothesis that while relaxation practices may have certain stress reduction effects, the effects are predominantly mediated by the mindfulness meditation practice. Furthermore, the long-term benefits of increased resilience observed in the Templestay program group suggest that the practice may be a possible treatment strategy in clinical populations, such as patients with depression and anxiety.

Intrinsic functional connectivity of blue and red brains: neurobiological evidence of different stress resilience between political attitudes.

Conservatives are more sensitive to threatening/anxious situations in perceptual and cognitive levels, experiencing emotional responses and stress, while liberals are more responsive to but tolerant of ambiguous and uncertain information. Interestingly, conservatives have greater psychological well-being and are more satisfied with their lives than liberals despite their psychological vulnerability to stress caused by threat and anxiety sensitivities. We investigated whether conservatives have greater resilience and self-regulation capacity, which are suggested to be psychological buffers that enhance psychological well-being, than liberals and moderates. We also explored associations between intrinsic functional brain organization and these psychological resources to expand our neurobiological understanding of self-regulatory processes in neuropolitics. We found that conservatives, compared to liberals and moderates, had greater psychological resilience and self-regulation capacity that were attributable to greater impulse control and causal reasoning. Stronger intrinsic connectivities between the orbitofrontal cortex (OFC) and precuneus and between the insula and frontal pole/OFC in conservatives were correlated with greater resilience and self-regulation capacity. These results suggest the neural underpinnings that may allow conservatives to manage the psychological stress and achieve greater life satisfaction. This study provides neuroscientific evidence for the different responses of liberals and conservatives to politically relevant social issues.

Defining data-driven subgroups of obsessive-compulsive disorder with different treatment responses based on resting-state functional connectivity.

Characterization of obsessive-compulsive disorder (OCD), like other psychiatric disorders, suffers from heterogeneities in its symptoms and therapeutic responses, and identification of more homogeneous subgroups may help to resolve the heterogeneity. We aimed to identify the OCD subgroups based on resting-state functional connectivity (rsFC) and to explore their differences in treatment responses via a multivariate approach. From the resting-state functional MRI data of 107 medication-free OCD patients and 110 healthy controls (HCs), we selected rsFC features, which discriminated OCD patients from HCs via support vector machine (SVM) analyses. With the selected brain features, we subdivided OCD patients into subgroups using hierarchical clustering analyses. We identified 35 rsFC features that achieved a high sensitivity (82.74%) and specificity (76.29%) in SVM analyses. The OCD patients were subdivided into two subgroups, which did not show significant differences in their demographic and clinical backgrounds. However, one of the OCD subgroups demonstrated more impaired rsFC that was involved either within the default mode network (DMN) or between DMN brain regions and other network regions. This subgroup also showed both lower improvements in symptom severity in the 16-week follow-up visit and lower responder percentage than the other subgroup. Our results highlight that not only abnormalities within the DMN but also aberrant rsFC between the DMN and other networks may contribute to the treatment response and support the importance of these neurobiological alterations in OCD patients. We suggest that abnormalities in these connectivity may play predictive biomarkers of treatment response, and aid to build more optimal treatment strategies.

Effect of tDCS on Aberrant Functional Network Connectivity in Refractory Hallucinatory Schizophrenia: A Pilot Study.

We aim to investigate the effect of fronto-temporal transcranial direct current stimulation (tDCS) on the interactions among functional networks and its association with psychotic symptoms. In this pilot study, we will determine possible candidate functional networks and an adequate sample size for future research. Seven schizophrenia patients with treatment-refractory auditory hallucinations underwent tDCS twice daily for 5 days. Resting-state fMRI data and measures of the severity of psychotic symptoms were acquired at baseline and after completion of the tDCS sessions. At baseline, decreased functional network interaction was negatively correlated with increased hallucinatory behavior. After tDCS, the previously reduced functional network connectivity significantly increased. Our results showed that fronto-temporal tDCS could possibly remediate aberrant hallucination-related functional network interactions in patients with schizophrenia.

Functional connectivity of the raphe nucleus as a predictor of the response to selective serotonin reuptake inhibitors in obsessive-compulsive disorder.

Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological agents for treating obsessive-compulsive disorder (OCD). However, because nearly half of patients show insufficient SSRI responses, serotonergic dysfunction in heterogeneous OCD patients should be investigated for precision medicine. We aimed to determine whether functional connectivity (FC) of the raphe nucleus (RN), the major source of most serotonergic neurons, was altered in OCD patients and could predict the SSRI response. A total of 102 medication-free OCD patients and 101 matched healthy control (HC) subjects participated in resting-state functional magnetic resonance imaging. Among them, 54 OCD patients were treated with SSRIs for 16 weeks, resulting in 26 responders and 28 nonresponders. Seed-based whole brain FC with the RN as a seed region was compared between the OCD and HC groups, as well as between SSRI responders and nonresponders. FC cluster values showing significant group differences were used to investigate factors correlated with symptomatic severity before treatment and predictive of SSRI response. Compared to HCs, OCD patients exhibited significantly larger FC between the RN and temporal cortices including the middle temporal gyrus (MTG), paracingulate gyrus, amygdala, hippocampus, putamen, thalamus, and brain stem. Greater RN-left MTG FC was positively correlated with OC symptom severity at baseline. In addition, larger FC of the RN-left MTG was also found in SSRI nonresponders compared to responders, which was a significant predictor of SSRI response after 16 weeks. The FC of RN may reflect the neurobiological underpinning of OCD and could aid future precision medicine as a differential brain-based biomarker.

Enhanced Attentional Network by Short-Term Intensive Meditation.

While recent studies have suggested behavioral effects of short-term meditation on the executive attentional functions, functional changes in the neural correlates of attentional networks after short-term meditation have been unspecified. Here, we conducted a randomized control trial to investigate the effects of a 4-day intensive meditation on the neural correlates of three attentional functions: alerting, orienting, and executive attention. Twenty-three participants in meditation practice and 14 participants in a relaxation retreat group performed attention network test (ANT) during functional magnetic resonance imaging both before and immediately after intervention. The meditation group showed significantly improved behavioral performance in the executive control network in ANT after the intervention. Moreover, neural activities in the executive control network, namely, the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC), were also significantly increased during the ANT after meditation. Interestingly, neural activity in the right ACC was significantly predicted by behavioral conflict levels in each individual in the meditation group, indicating significant effects of the program on the executive control network. Moreover, brain regions associated with the alerting and orienting networks also showed enhanced activity during the ANT after the meditation. Our study provides novel evidence on the enhancement of the attentional networks at the neural level via short-term meditation. We also suggest that short-term meditation may be beneficial to individuals at high risk of cognitive deficits by improving neural mechanisms of attention.

The Immediate and Sustained Positive Effects of Meditation on Resilience Are Mediated by Changes in the Resting Brain.

While recent studies have explored the maintenance of the effect of meditation on stress resilience, the underlying neural mechanisms have not yet been investigated. The present study conducted a highly controlled residential study of a 4-day meditation intervention to investigate the brain functional changes and long-term effects of meditation on mindfulness and resilience. Thirty participants in meditation practice and 17 participants in a relaxation retreat (control group) underwent magnetic resonance imaging scans at baseline and post-intervention and completed the Cognitive and Affective Mindfulness Scale (CAMS) and Resilience Quotient Test (RQT) at baseline, post-intervention, and the 3-month follow-up. All participants showed increased CAMS and RQT scores post-intervention, but only the meditation group sustained the enhancement after 3 months. Resting-state functional connectivity (rsFC) between the left rostral anterior cingulate cortex (rACC) and the dorsomedial prefrontal cortex (dmPFC), precuneus, and angular gyrus was significantly increased post-intervention in the meditation group compared with the relaxation group. The changes in rACC-dmPFC rsFC mediated the relationship between the changes in the CAMS and RQT scores and correlated with the changes in the RQT score both immediately and at 3 months post-intervention. Our findings suggest that increased rACC-dmPFC rsFC via meditation causes an immediate enhancement in resilience that is sustained. Since resilience is known to be associated with the preventative effect of various psychiatric disorders, the improvement in stress-related neural mechanisms may be beneficial to individuals at high clinical risk.

Higher extrinsic and lower intrinsic connectivity in resting state networks for professional Baduk (Go) players.

Introduction: Dedication and training to a profession results in a certain level of expertise. This expertise, like any other skill obtained in our lifetime, is encoded in the brain and may be reflected in our brain's connectome. This property can be observed by mapping resting state connectivity. In this study, we examine the differences in resting state functional connectivity in four major networks between professional "Baduk" (Go) players and normal subjects. Methods: Resting state fMRI scans were acquired for professional "Baduk" (Go) players and normal controls. Major resting state networks were identified using independent component analysis and compared between the two groups. Networks which were compared include the default mode network, the left and right fronto-parietal network, and the salience network. Results: We found that normal subjects showed increased connectivity within certain areas of each target network. Professional players, however, showed higher connectivity to regions outside the traditional regions of each given network. Close examination of these regions revealed that regions shown to have higher connectivity in professional players have been revealed to be relevant in expertise for board games. Conclusion: The findings in this study suggest that continuous training results in greater integration between regions and networks, which are necessary for high-level performance. The differences observed in our study between normal controls and professional players also shed light on the difference in brain connectivity which can arise through lifestyle and specialization in a specific field.