Impact of combination of intermittent theta burst stimulation and methadone maintenance treatment in individuals with opioid use disorder: A comparative study.

Prior studies indicate that subjects undergoing methadone maintenance therapy (MMT) may experience anxiety, depression and cravings. This study aimed to explore the impact of intermittent theta burst stimulation (iTBS)-MMT combination on craving and emotional symptoms of opioid use disorder. This comparative study included subjects with opioid use disorder at the Methadone Maintenance Clinic of Pudong New Area between September 2019 and March 2020. The subjects were divided into two groups: those who received iTBS-MMT combination treatment (iTBS-MMT) and those who received MMT treatment and sham stimulation treatment (MMT). Outcomes were reduction rate of anxiety, depression and craving. Anxiety was measured by Hamilton Anxiety (HAMA) scale, depression was determined by Hamilton Depression (HAMD) scale and craving was analyzed using visual analog scale. A total of 76 subjects completed the treatment, with 38 subjects in each group. Twenty days after treatment, subjects in the iTBS-MMT group had significant improvement of anxiety (HAMA reduction rate), depression (HAMD reduction rate) and craving (Craving reduction rate) reduction rate compared with MMT group. iTBS-MMT combination treatment may produce better drug craving reduction and emotional improvement than MMT alone.

Transcriptional level of inflammation markers associates with short-term brain structural changes in first-episode schizophrenia.

BACKGROUND: Inflammation has been implicated in the pathology of schizophrenia and may cause neuronal cell death and dendrite loss. Neuroimaging studies have highlighted longitudinal brain structural changes in patients with schizophrenia, yet it is unclear whether this is related to inflammation. We aim to address this question, by relating brain structural changes with the transcriptional profile of inflammation markers in the early stage of schizophrenia. METHODS: Thirty-eight patients with first-episode schizophrenia and 51 healthy controls were included. High-resolution T1-weighted magnetic resonance imaging (MRI) and clinical assessments were performed at baseline and 2 ~ 6 months follow-up for all subjects. Changes in the brain structure were analyzed using surface-based morphological analysis and correlated with the expression of immune cells-related gene sets of interest reported by previous reviews. Transcriptional data were retrieved from the Allen Human Brain Atlas. Furthermore, we examined the brain structural changes and peripheral inflammation markers in association with behavioral symptoms and cognitive functioning in patients. RESULTS: Patients exhibited accelerated cortical thickness decrease in the left frontal cortices, less decrease or an increase in the superior parietal lobule and right lateral occipital lobe, and increased volume in the bilateral pallidum, compared with controls. Changes in cortical thickness correlated with the transcriptional level of monocyte across cortical regions in patients (r = 0.54, p < 0.01), but not in controls (r = - 0.05, p = 0.76). In addition, cortical thickness change in the left superior parietal lobule positively correlated with changes in digital span-backward test scores in patients. CONCLUSIONS: Patients with schizophrenia exhibit regional-specific cortical thickness changes in the prefrontal and parietooccipital cortices, which is related to their cognitive impairment. Inflammation may be an important factor contributing to cortical thinning in first-episode schizophrenia. Our findings suggest that the immunity-brain-behavior association may play a crucial role in the pathogenesis of schizophrenia.

Alterations in brain iron deposition with progression of late-life depression measured by magnetic resonance imaging (MRI)-based quantitative susceptibility mapping.

Background: Previous studies have revealed abnormality of iron deposition in the brain of patients with depression. The progression of iron deposition associated with depression remains to be elucidated. Methods: This is a longitudinal study. We explored brain iron deposition with disease progression in 20 patients older than 55 years with depression and on antidepressants, using magnetic resonance imaging (MRI)-based quantitative susceptibility mapping (QSM). Magnetic susceptibility values of the whole brain were compared between baseline and approximately one-year follow-up scans using permutation testing. Furthermore, we examined the relationship of changes between the susceptibility values and disease improvement using Spearman's partial correlation analysis, controlling for age, gender, and the visit interval. Results: Compared to the initial scan, increased magnetic susceptibility values were found in the medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (dACC), occipital areas, habenula, brainstem, and cerebellum (P<0.05, corrected). The susceptibility values decreased in the dorsal part of the mPFC, middle and posterior cingulate cortex (MCC and PCC), right postcentral gyrus, right inferior parietal lobule, right precuneus, right supramarginal gyrus, left lingual gyrus, left dorsal striatum, and right thalamus (P<0.05, corrected). Notably, the increase in susceptibility values at the mPFC and dACC negatively correlated with the changes in depression scores, as calculated using the Hamilton Depression Scale (HAMD) (r=-0.613, P=0.009), and the increase in susceptibility values at the cerebellum and habenula negatively correlated with the changes in cognitive scores, which were calculated using the Mini-Mental State Examination (MMSE) (cerebellum: r=-0.500, P=0.041; habenula: r=-0.588, P=0.013). Additionally, the decreased susceptibility values at the white matter near the mPFC (anterior corona radiata) also correlated with the changes in depression scores (r=-0.541, P=0.025), and the decreased susceptibility values at the left lingual gyrus correlated with the changes in cognitive scores (r=-0.613, P=0.009). Conclusions: Our study identified brain areas where iron deposition changed with the progression of depression while on antidepressants. The linear relationship of changes in the magnetic susceptibility values in the mPFC, dACC, and some subcortical areas with changes in depression symptoms and cognitive functions of patients is highlighted. Our results strengthen the understanding of the alterations of brain iron levels associated with disease progression in patients with late-life depression.

Power signatures of habenular neuronal signals in patients with bipolar or unipolar depressive disorders correlate with their disease severity.

The habenula is an epithalamic structure implicated in negative reward mechanisms and plays a downstream modulatory role in regulation of dopaminergic and serotonergic functions. Human and animal studies show its hyperactivity in depression which is curtailed by the antidepressant response of ketamine. Deep brain stimulation of habenula (DBS) for major depression have also shown promising results. However, direct neuronal activity of habenula in human studies have rarely been reported. Here, in a cross-sectional design, we acquired both spontaneous resting state and emotional task-induced neuronal recordings from habenula from treatment resistant depressed patients undergoing DBS surgery. We first characterise the aperiodic component (1/f slope) of the power spectrum, interpreted to signify excitation-inhibition balance, in resting and task state. This aperiodicity for left habenula correlated between rest and task and which was significantly positively correlated with depression severity. Time-frequency responses to the emotional picture viewing task show condition differences in beta and gamma frequencies for left habenula and alpha for right habenula. Notably, alpha activity for right habenula was negatively correlated with depression severity. Overall, from direct habenular recordings, we thus show findings convergent with depression models of aberrant excitatory glutamatergic output of the habenula driving inhibition of monoaminergic systems.

Bilateral Habenula deep brain stimulation for treatment-resistant depression: clinical findings and electrophysiological features.

Deep brain stimulation (DBS) of structures in the brain's reward system is a promising therapeutic option for patients with treatment-resistant depression (TRD). Recently, DBS of the habenula (HB) in the brain's anti-reward system has also been reported to alleviate depressive symptoms in patients with TRD or bipolar disorder (BD). In this pilot open-label prospective study, we explored the safety and clinical effectiveness of HB-DBS treatment in seven patients with TRD or BD. Also, local field potentials (LFPs) were recorded from the patients' left and right HB to explore the power and asymmetry of oscillatory activities as putative biomarkers of the underlying disease state. At 1-month follow-up (FU), depression and anxiety symptoms were both reduced by 49% (n = 7) along with substantial improvements in patients' health status, functional impairment, and quality of life. Although the dropout rate was high and large variability in clinical response existed, clinical improvements were generally maintained throughout the study [56%, 46%, and 64% reduction for depression and 61%, 48%, and 70% reduction for anxiety at 3-month FU (n = 5), 6-month FU (n = 5), and 12-month FU (n = 3), respectively]. After HB-DBS surgery, sustained improvements in mania symptoms were found in two patients who presented with mild hypomania at baseline. Another patient, however, experienced an acute manic episode 2 months after surgery that required hospitalization. Additionally, weaker and more symmetrical HB LFP oscillatory activities were associated with more severe depression and anxiety symptoms at baseline, in keeping with the hypothesis that HB dysfunction contributes to MDD pathophysiology. These preliminary findings indicate that HB-DBS may offer a valuable treatment option for depressive symptoms in patients who suffer from TRD or BD. Larger and well-controlled studies are warranted to examine the safety and efficacy of HB-DBS for treatment-refractory mood disorders in a more rigorous fashion.

Family accommodation in Chinese individuals with obsessive-compulsive disorder.

Family accommodation is a common, treatment-relevant construct related to obsessive-compulsive disorder (OCD) severity and treatment outcome. This initial study examined the nature, incidence, and clinical correlates of family accommodation in Chinese adults with OCD and their relative or person in a close relationship. One hundred four outpatients diagnosed with OCD completed self-report measures of obsessive-compulsive, anxiety, and depression symptoms. Additionally, the individuals with OCD and a relative completed a measure of family accommodation and impairment. Patient-reports of family accommodation were significantly correlated with OCD symptomology and severity. A multiple linear regression indicated that OCD symptomology was a significant predictor of family accommodation, but anxiety, stress, and depression were not. In addition, the current Chinese sample demonstrated greater levels of family accommodation than previous English-speaking samples. Potential explanations and implications of the high levels of reported family accommodation are discussed. Family accommodation could play a significant role in OCD development and/or maintenance in China. Future research considerations are discussed.

Anterior limb of the internal capsule tractography: relationship with capsulotomy outcomes in obsessive-compulsive disorder.

OBJECTIVES: Surgical procedures targeting the anterior limb of the internal capsule (aLIC) can be effective in patients with selected treatment-refractory obsessive-compulsive disorder (OCD). The aLIC consists of white-matter tracts connecting cortical and subcortical structures and show a topographical organisation. Here we assess how aLIC streamlines are affected in OCD compared with healthy controls (HCs) and which streamlines are related with post-capsulotomy improvement. METHODS: Diffusion-weighted MRI was used to compare white-matter microstructure via the aLIC between patients with OCD (n=100, 40 women, mean of age 31.8 years) and HCs (n=88, 39 women, mean of age 29.6 years). For each individual, the fractional anisotropy (FA) and streamline counts were calculated for each white-matter fibre bundle connecting a functionally defined prefrontal and subcortical region. Correlations between tractography measures and pre-capsulotomy and post-capsulotomy clinical outcomes (in obsessive-compulsive, anxiety and depression scores 6 months after surgery) were assessed in 41 patients with OCD. RESULTS: Hierarchical clustering dendrograms show an aLIC organisation clustering lateral and dissociating ventral and dorsal prefrontal-thalamic streamlines, findings highly relevant to surgical targeting. Compared with HCs, patients with OCD had lower aLIC FA across multiple prefrontal cortical-subcortical regions (p<0.0073, false discovery rate-adjusted). Greater streamline counts of the dorsolateral prefrontal-thalamic tracts in patients with OCD predicted greater post-capsulotomy obsessive-compulsive improvement (p=0.016). In contrast, greater counts of the dorsal cingulate-thalamic streamlines predicted surgical outcomes mediated by depressive and anxiety improvements. CONCLUSIONS: These findings shed light on the critical role of the aLIC in OCD and may potentially contribute towards precision targeting to optimise outcomes in OCD.

Sustained Relief after Pallidal Stimulation Interruption in Tourette's Syndrome Treated with Simultaneous Capsulotomy.

INTRODUCTION: Globus pallidus internus (GPi) deep brain stimulation (DBS) combined with anterior capsulotomy offers a promising treatment option for severe medication-refractory cases of Tourette's syndrome (TS) with psychiatric comorbidities. Several patients treated with this combined surgery experienced sustained relief after discontinuation of stimulation over the course of treatment. METHODS: Retrospectively, the medical records and clinical outcomes were reviewed of 8 patients (6 men; 2 women with mean age of 20.3 years) who had undergone bilateral GPi-DBS combined with anterior capsulotomy for medically intractable TS and psychiatric comorbidities. All patients had experienced an accidental interruption or intentional withdrawal of pallidal stimulation during treatment. RESULTS: The widespread clinical benefits achieved during the combined treatment were fully maintained after intentional or accidental DBS discontinuation. The improvement in overall tic symptoms achieved was on average 78% at the follow-up or close to the DBS discontinuation, while it was 83% at last follow-up (LFU). At LFU, most patients had functionally recovered; exhibited only mild tics; displayed minor or no obsessive-compulsive disorder symptoms, anxiety, or depression; and experienced a much better quality of life. CONCLUSION: Bilateral GPi-DBS combined with anterior capsulotomy appears to result in marked and sustained improvements in TS symptoms and psychiatric comorbidities, which are fully maintained over time, even without pallidal stimulation.

The Obsessive-Compulsive Inventory-Revised: Replication of the psychometric properties in China.

The aim of this study is to replicate the findings from previous research about the psychometric properties of the Mandarin Chinese version of the Obsessive-Compulsive Inventory-Revised (OCI-R), which assesses the presence of symptoms obsessive-compulsive disorder and the distress associated with those symptoms. The final clinical sample included 80 participants from multiple psychiatric outpatient clinics in China. Participants completed the following questionnaires: the OCI-R, the Depression, Anxiety, and Stress Scale (DASS-21), the Yale-Brown Obsessive-Compulsive Scale-II (Y-BOCS-II), and the Clinical Global Impressions Scale, Severity (CGI-S). The Mandarin Chinese version of the OCI-R demonstrated good internal consistency for the total scale and each subscale. Good convergent and divergent validity was established. The Mandarin Chinese version of the OCI-R demonstrated good psychometric properties. Further research is needed to examine the factor structure of the Chinese version of the OCI-R and the extent to which it aligns with the original version.

The Chinese version of obsessive compulsive drug use scale: validation in outpatient methadone maintenance treatment program.

BACKGROUND: The Obsessive Compulsive Drug Use Scale (OCDUS) measures the overall craving level within a period from a multidimensional perspective. However, no studies have addressed the validity of the new OCDUS factor structure, presented in 2016, in China. Additionally, there is lack of evidence on the interaction among risk factors for relapse. We aimed to assess the psychometric properties of the scores of the Chinese version of the OCDUS in patients with heroin dependence receiving methadone maintenance treatment (MMT). Further, we aimed to assess the correlations of the OCDUS scores with withdrawal symptoms, depression, anxiety, and nicotine dependence. METHODS: We enrolled 113 adults (age 32-64 years) and administered them with the OCDUS, Subjective Opioid Withdrawal Scale (SOWS), Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI), and Fagerstrom Test for Nicotine Dependence (FTND). RESULTS: Exploratory factor analysis identified a 3-dimensional component that included "Frequency of craving," "Inference of heroin," and "Control of heroin." These factors showed acceptable internal consistency, adequate item-total correlations, and significant item-subscale correlations. There was no correlation between the OCUDS scores and age, education, duration of receiving MMT, and MMT dosages. However, there was a significant correlation between the OCDUS total scores and the SOWS, STAI, BDI-II, and FTND scores. The scores of all the subscales were associated with the SOWS scores; further, the scores of the first two subscales were associated with BDI-II scores while only the scores of the first subscale were associated with the FTND scores. CONCLUSIONS: Our findings support the reliability and structure validity of the OCDUS scores. Heroin craving, withdrawal symptoms, negative emotions, and nicotine dependence, which are considered as risk factors for heroin relapse, might interact with each other. There is a need for further studies on the underlying mechanism of these clinical phenomena.

Habenula deep brain stimulation for intractable schizophrenia: a pilot study.

Schizophrenia is a psychiatric disorder associated with significant morbidity and mortality. Although antipsychotic medications and electroconvulsive therapy can be used to manage the clinical symptoms of schizophrenia, a substantial portion (10%-30%) of patients do not clinically respond to these treatments or cannot tolerate the side effects. Recently, deep brain stimulation (DBS) has emerged as a promising safe and effective therapeutic intervention for various psychiatric disorders. Here, the authors explore the utility of DBS of the habenula (HB) in the clinical management of 2 young adult male patients with severe, chronic, and treatment-resistant schizophrenia. After HB DBS surgery, both patients experienced improvements in clinical symptoms during the first 6 months of treatment. However, only 1 patient retained the clinical benefits and reached a favorable outcome at 12-month follow-up. The symptoms of the other patient subsequently worsened and became so profound that he needed to be hospitalized at 10-month follow-up and withdrawn from further study participation. It is tentatively concluded that HB DBS could ultimately be a relatively safe and effective surgical intervention for certain patients with treatment-resistant schizophrenia.

An Evaluation of the Psychometric Properties of the Sheehan Disability Scale in a Chinese Psychotherapy-Seeking Sample.

Although the Sheehan Disability Scale (SDS) is one of the most extensively used and tested disability measurements, there has only been one psychometric evaluation of its properties in a Chinese-speaking population. Here, we provide a comprehensive psychometric assessment of the scale in 465 Mandarin-speakers who were accessing information online regarding psychotherapy. Principal component analysis and subsequent confirmatory factor analysis indicated that the SDS is one-dimensional (normed fit index = 0.976, non-normed fit index = 0.97, comparative fit index = 0.98, goodness-of-fit index = 0.967, standardized root mean-square residual = 0.023, root mean-square error of approximation = 0.149). The SDS exhibited excellent internal consistency (α = .89) and moderate test-retest reliability when readministered approximately 8 days later (intraclass correlation coefficient = 0.55). Convergent validity was demonstrated by strong relationships with other measures of functional impairment (FI), while divergent validity was evidenced by fair correlation with a treatment ambivalence measure. Known-groups validity analyses showed that high FI was associated with significantly higher clinical scores of anxiety, depression, and obsessive-compulsive symptoms. Regression analysis indicated that the Depression Anxiety Stress Scale-21 score accounted for 37.6% of variance in FI. Overall, these findings support the reliability and validity of the SDS when used in Chinese treatment-seeking individuals, as well its usefulness as an online screening tool of FI.

Development and psychometric evaluation of the Mandarin Chinese version of the Yale-Brown Obsessive-Compulsive Scale - Second Edition

Objective: To examine the psychometric properties of the Chinese version of the Yale-Brown Obsessive Compulsive Scale - Second Edition (Y-BOCS-II). Method: A total of 86 adults with a primary diagnosis of obsessive-compulsive disorder (OCD), ranging in age from 15 to 78 years, participated in the study. Participants were administered the Y-BOCS-II by a trained clinician who also rated overall illness severity on two additional measures. Patients completed the Obsessive Compulsive Inventory-Revised and Depression Anxiety Stress Scale-21. Results: Results indicated high internal consistency and fair 1-week test retest reliability. The Y-BOCS-II scales correlated strongly with clinician-rated obsessive-compulsive severity and modestly with self-reported obsessive-compulsive symptom frequency and distress. The relationship between Y-BOCS-II total score and depressive and anxiety symptoms was strong, which may reflect high rates of comorbid conditions in this sample or the linkage between obsessive-compulsive symptom severity and distress. Factor analysis demonstrated a two-factor structure consisting of obsession and compulsion factors, with interference due to obsessions cross-loading. Conclusions: Overall, these results support the use of the Y-BOCS-II among individuals from China. Future study by an independent group is necessary to replicate these findings, as well as investigate interrater reliability and treatment sensitivity.

Incidence and clinical correlates of anger attacks in Chinese patients with obsessive-compulsive disorder.

OBJECTIVE: Anger attacks have been observed in patients with obsessive-compulsive disorder (OCD), often triggered by obsessional triggers. However, few studies have reported the clinical characteristics and correlates of anger attacks among Chinese patients with OCD. METHODS: A total of 90 adults with a primary diagnosis of OCD, ranging from 15 to 78 years old, participated in the study. Participants were administered the Rage Outbursts and Anger Rating Scale (ROARS), Yale-Brown Obsessive-Compulsive Scale-Second Edition, and Brown Assessment of Beliefs Scale by a trained clinician. Patients completed the Obsessive-Compulsive Inventory-Revised and Depression Anxiety Stress Scale-21. RESULTS: A total of 31.3% of participants reported anger outbursts in the past week, and ROARS scores had no significant correlation with age, duration of illness, OCD severity, depression, or stress. However, ROARS scores were negatively related to education level, and positively related to obsessing symptoms and anxiety. CONCLUSIONS: These data suggest that anger attacks are relatively common in Chinese patients with OCD. The severity of anger attacks is related to educational level, obsessing symptoms, and anxiety, which may be a latent variable reflecting executive functioning and emotion regulation skills.

Development and psychometric evaluation of the Mandarin Chinese version of the Yale-Brown Obsessive-Compulsive Scale - Second Edition.

OBJECTIVE: To examine the psychometric properties of the Chinese version of the Yale-Brown Obsessive Compulsive Scale - Second Edition (Y-BOCS-II). METHOD: A total of 86 adults with a primary diagnosis of obsessive-compulsive disorder (OCD), ranging in age from 15 to 78 years, participated in the study. Participants were administered the Y-BOCS-II by a trained clinician who also rated overall illness severity on two additional measures. Patients completed the Obsessive Compulsive Inventory-Revised and Depression Anxiety Stress Scale-21. RESULTS: Results indicated high internal consistency and fair 1-week test retest reliability. The Y-BOCS-II scales correlated strongly with clinician-rated obsessive-compulsive severity and modestly with self-reported obsessive-compulsive symptom frequency and distress. The relationship between Y-BOCS-II total score and depressive and anxiety symptoms was strong, which may reflect high rates of comorbid conditions in this sample or the linkage between obsessive-compulsive symptom severity and distress. Factor analysis demonstrated a two-factor structure consisting of obsession and compulsion factors, with interference due to obsessions cross-loading. CONCLUSIONS: Overall, these results support the use of the Y-BOCS-II among individuals from China. Future study by an independent group is necessary to replicate these findings, as well as investigate interrater reliability and treatment sensitivity.

Pallidal deep brain stimulation combined with capsulotomy for Tourette's syndrome with psychiatric comorbidity.

OBJECTIVE: A current challenge is finding an effective and safe treatment for severely disabled patients with Tourette's syndrome (TS) and comorbid psychiatric disorders, in whom conventional treatments have failed. The authors aimed to evaluate the utility of globus pallidus internus deep brain stimulation (GPi-DBS) combined with bilateral anterior capsulotomy in treating these clinically challenging patients. METHODS: The authors conducted a retrospective review of the clinical history and outcomes of 10 severely disabled patients with treatment-refractory TS and a psychiatric comorbidity, who had undergone GPi-DBS combined with bilateral anterior capsulotomy in their hospital. At the time of surgery, patients presented mainly with obsessive-compulsive disorder and affective disorders. Clinical outcome assessments of tic and psychiatric symptoms, as well as of general adaptive functioning and quality of life, were performed at the time of surgery and at 6, 12, and between 24 and 96 months postsurgery. RESULTS: After surgery, all patients showed significant progressive improvements in tic and psychiatric symptoms, along with improvements in general adaptive functioning and quality of life. Tic alleviation reached 64% at 12 months and 77% at the last follow-up on the Yale Global Tic Severity Scale. At the final follow-up, patients had functionally recovered and displayed no or only mild tic and psychiatric symptoms. All patients tolerated treatment reasonably well, with no serious side effects. CONCLUSIONS: GPi-DBS combined with bilateral anterior capsulotomy seems to offer major clinical benefits to severely disabled patients with otherwise treatment-refractory TS and psychiatric comorbidities.

Abnormal Voxel-Wise Degree Centrality in Patients With Late-Life Depression: A Resting-State Functional Magnetic Resonance Imaging Study.

OBJECTIVES: Late-life depression (LLD) has negative impacts on somatic, emotional and cognitive domains of the lives of patients. Elucidating the abnormality in the brain networks of LLD patients could help to strengthen the understanding of LLD pathophysiology, however, the studies exploring the spontaneous brain activity in LLD during the resting state remain limited. This study aimed at identifying the voxel-level whole-brain functional connectivity changes in LLD patients. METHODS: Fifty patients with late-life depression (LLD) and 33 healthy controls were recruited. All participants underwent a resting-state functional magnetic resonance imaging scan to assess the voxel-wise degree centrality (DC) changes in the patients. Furthermore, DC was compared between two patient subgroups, the late-onset depression (LOD) and the early-onset depression (EOD). RESULTS: Compared with the healthy controls, LLD patients showed increased DC in the inferior parietal lobule, parahippocampal gyrus, brainstem and cerebellum (p < 0.05, AlphaSim-corrected). LLD patients also showed decreased DC in the somatosensory and motor cortices and cerebellum (p < 0.05, AlphaSim-corrected). Compared with EOD patients, LOD patients showed increased centrality in the superior and middle temporal gyrus and decreased centrality in the occipital region (p < 0.05, AlphaSim-corrected). No significant correlation was found between the DC value and the symptom severity or disease duration in the patients after the correction for multiple comparisons. CONCLUSIONS: These findings indicate that the intrinsic abnormality of network centrality exists in a wide range of brain areas in LLD patients. LOD patients differ with EOD patients in cortical network centrality. Our study might help to strengthen the understanding of the pathophysiology of LLD and the potential neural substrates underlie related emotional and cognitive impairments observed in the patients.

Dissociable Frontostriatal Connectivity: Mechanism and Predictor of the Clinical Efficacy of Capsulotomy in Obsessive-Compulsive Disorder.

BACKGROUND: Little is known about the neural mechanism and response variability underlying neurosurgical interventions for intractable obsessive-compulsive disorder (OCD). METHODS: Of 81 OCD patients screened for capsulotomy identified in our institutional database, 36 patients with clinical assessment before and after capsulotomy and imaging data (9 of 36 patients without postoperative imaging data used as an independent test group), and 29 healthy control subjects were retrospectively recruited. Twenty of 36 patients (56%) responded to the lesion procedure (determined as a ≥35% reduction in Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score). Seed-based (i.e., ventral and dorsal caudate, medial dorsal thalamus, and ventral and dorsal putamen) resting-state functional connectivity was used to examine alterations in frontostriatal circuitry after capsulotomy. RESULTS: The Y-BOCS score significantly decreased (p < .001) after capsulotomy in OCD patients. Functional connectivity between the ventral striatum/nucleus accumbens and the dorsal anterior cingulate cortex was reduced (p < .05, corrected) after the surgical procedure. Moreover, change in connectivity significantly correlated with alteration in Y-BOCS score (r = .41, p = .033). In addition, preoperative connectivity between the dorsal caudate and the dorsal anterior cingulate cortex could differentiate nonresponders from responders and predict changes in Y-BOCS score (R2 = .23, F1,25 = 7.56, p = .011), which was generalized in an independent test group. CONCLUSIONS: We demonstrated that restoration of ventral frontostriatal connectivity was associated with clinical improvement in refractory OCD, suggesting a therapeutic mechanism of capsulotomy. Moreover, preoperative variations in dorsal frontostriatal connectivity predicted clinical response, which may offer a predictor of treatment outcome.

Effects of Anterior Capsulotomy on Decision Making in Patients with Refractory Obsessive-Compulsive Disorder.

Despite various lines of evidence implicating impaired decision-making ability in individuals with obsessive-compulsive disorder (OCD), neuropsychological investigation has generated inconsistent findings. Although the cortico-striato-thalamo-cortical (CSTC) circuitry has been suggested, the involvement of the cortex has not yet been fully demonstrated. Moreover, it is unknown whether surgical intervention on the CSTC circuitry results in a predicted improvement of decision-making ability of OCD. Here we present a study of decision making based on the Iowa Gambling Task (IGT) to investigate decision making in a large sample of individuals with treatment-resistant OCD with and without anterior capsulotomy (AC). Task performance was evaluated in healthy subjects, individuals with OCD that had not undergone surgery, and postsurgical OCD patients with AC. The latter group was further divided into a short-term postsurgical group and a long-term postsurgical group. We found that the OCD patients without surgery performed significantly worse than the healthy controls on the IGT. There were no significant differences in decision-making between the presurgical OCD patients and those at the short-term postsurgical follow-up. Decision-making ability of the long-term postsurgical OCD patients was improved to the level comparable to that of healthy controls. All clinical symptoms (OCD, depression, and anxiety) assessed by psychiatric rating scales were significantly alleviated post-surgically, but exhibited no correlation with their IGT task performance. Our findings provide strong evidence that OCD is linked to impairments in decision-making ability; that impaired CSTC circuitry function is directly involved in the manifestation of OCD; and that AC related improvements in cognitive functions are caused by long-term plasticity in the brain circuitry.