A systematic review of focused ultrasound for psychiatric disorders: current applications, opportunities, and challenges.

OBJECTIVE: Advancements in MRI-guided focused ultrasound (MRgFUS) technology have led to the successful treatment of select movement disorders. Based on the comparative success between ablation and deep brain stimulation, interest arises in focused ultrasound (FUS) as a promising treatment modality for psychiatric illnesses. In this systematic review, the authors examined current applications of FUS for psychiatric conditions and explored its potential opportunities and challenges. METHODS: The authors performed a comprehensive review using the PRISMA guidelines of studies investigating psychiatric applications for FUS. Articles indexed on PubMed between 2014 to 2024 were included. The authors synthesized the psychiatric conditions treated, neural targets, outcomes, study design, and sonication parameters, and they reviewed important considerations for the treatment of psychiatric disorders with FUS. They also discussed active clinical trials in this research domain. RESULTS: Of 250 articles, 10 met the inclusion criteria. Eight articles investigated the clinical, safety, and imaging correlates of MRgFUS in obsessive-compulsive disorder (OCD), whereas 3 examined treatment-resistant depression. Bilateral anterior capsulotomy resulted in a full responder rate of 67% (≥ 35% reduction in the Yale-Brown Obsessive-Compulsive Scale score) and 33% (≥ 50% reduction in the score on the Hamilton Rating Scale for Depression) in OCD and treatment-resistant depression, respectively. Sonications ranged from 8 to 36 with targeted lesional temperatures of 51°C-56°C. Lesions in the anterodorsal aspect of the anterior limb of the internal capsule (ALIC) and increased functional connectivity to the left dorsolateral prefrontal cortex and dorsal anterior cingulate cortex significantly predicted reduction in symptoms among patients with OCD, with decreases in beta-band activity in the frontocentral and temporal regions associated with reductions in depression and anxiety. Treatment of the nucleus accumbens with low-intensity FUS (LIFU) in patients with opioid-use disorders resulted in significant reductions in cue-reactive cravings, lasting up to 90 days. No serious adverse events were reported, including cognitive decline. Side effects were generally mild and transient, consisting of headaches, pin-site swelling, and nausea. Fourteen active clinical trials were identified, primarily targeting depression with LIFU. CONCLUSIONS: Currently, FUS for psychiatric conditions is centered on OCD, with early pilot studies demonstrating promising safety and efficacy. Further research expanding on defining optimal patient selection, study design, intensity, and sonication parameters is warranted, particularly as FUS expands to other psychiatric illnesses and incorporates LIFU paradigms. Ethical considerations such as patient consent and equitable access also remain paramount.

No significant alteration in white matter microstructure in first-degree relatives of patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is characterized by structural alteration within white matter tissues of cortico-striato-thalamo-cortical, temporal and occipital circuits. However, the presence of microstructural changes in the white matter tracts of unaffected first-degree relatives of patients with OCD as a vulnerability marker remains unclear. Therefore, here, diffusion-tensor magnetic resonance imaging (DTI) data were obtained from 29 first-degree relatives of patients with OCD and 59 healthy controls. We investigated the group differences in FA using whole-brain analysis (DTI analysis). For additional regions of interest (ROI) analysis, we focused on the posterior thalamic radiation and sagittal stratum, shown in recent meta-analysis of patients with OCD. In both whole-brain and ROI analyses, using a strict statistical threshold (family-wise error rate [FWE] corrected p<.05 for whole-brain analyses, and p<.0125 (0.05/4) with Bonferroni correction for ROI analyses), we found no significant group differences in FA. Subtle reductions were observed in the anterior corona radiata, forceps minor, cingulum bundle, and corpus callosum only when a lenient statistical was applied (FWE corrected p<.20). These findings suggest that alterations in the white matter microstructure of first-degree relatives, as potential vulnerability markers for OCD, are likely subtle.

Individualized functional connectome abnormalities obtained using two normative model unveil neurophysiological subtypes of obsessive compulsive disorder.

The high heterogeneity observed among patients with obsessive-compulsive disorder (OCD) underscores the need to identify neurophysiological OCD subtypes to facilitate personalized diagnosis and treatment. In this study, our aim was to identify potential OCD subtypes based on individualized functional connectome abnormalities. We recruited a total of 99 patients with OCD and 104 healthy controls (HCs) matched for demographic characteristics. Individualized functional connectome abnormalities were obtained using normative models of functional connectivity strength (FCS) and used as features to unveil OCD subtypes. Sensitivity analyses were conducted to assess the reproducibility and robustness of the clustering outcomes. Patients exhibited significant intersubject heterogeneity in individualized functional connectome abnormalities. Two subtypes with distinct patterns of FCS abnormalities relative to HCs were identified. Subtype 1 patients primarily exhibited significantly decreased FCS in regions including the frontal gyrus, insula, hippocampus, and precentral/postcentral gyrus, whereas subtype 2 patients demonstrated increased FCS in widespread brain regions. When all patients were combined, no significant differences were observed. Additionally, the identified subtypes showed significant differences in age of onset. Furthermore, sensitivity analyses confirmed the reproducibility of our subtyping results. In conclusion, the identified OCD subtypes shed new light on the taxonomy and neurophysiological heterogeneity of OCD.

Exploring functional connectivity in large-scale brain networks in obsessive-compulsive disorder: a systematic review of EEG and fMRI studies.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric condition that is difficult to treat due to our limited understanding of its pathophysiology. Functional connectivity in brain networks, as evaluated through neuroimaging studies, plays a pivotal role in understanding OCD. While both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been extensively employed in OCD research, few have fully synthesized their findings. To bridge this gap, we reviewed 166 studies (10 EEG, 156 fMRI) published up to December 2023. In EEG studies, OCD exhibited lower connectivity in delta and alpha bands, with inconsistent findings in other frequency bands. Resting-state fMRI studies reported conflicting connectivity patterns within the default mode network (DMN) and sensorimotor cortico-striato-thalamo-cortical (CSTC) circuitry. Many studies observed decreased resting-state connectivity between the DMN and salience network (SN), implicating the 'triple network model' in OCD. Task-related hyperconnectivity within the DMN-SN and hypoconnectivity between the SN and frontoparietal network suggest OCD-related cognitive inflexibility, potentially due to triple network dysfunction. In conclusion, our review highlights diverse connectivity differences in OCD, revealing complex brain network interplay that contributes to symptom manifestation. However, the presence of conflicting findings underscores the necessity for targeted research to achieve a comprehensive understanding of the pathophysiology of OCD.

Regional brain activity and connectivity associated with childhood trauma in drug-naive patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors, with childhood trauma recognized as a contributing factor to its pathophysiology. This study aimed to delineate brain functional aberrations in OCD patients and explore the association between these abnormalities and childhood trauma, to gain insights into the neural underpinnings of OCD. Forty-eight drug-naive OCD patients and forty-two healthy controls (HC) underwent resting-state functional magnetic resonance imaging and clinical assessments, including the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Childhood Trauma Questionnaire-Short Form (CTQ-SF). Compared to HCs, OCD patients exhibited significantly decreased amplitude of low-frequency fluctuations (ALFF) in the right cerebellum, decreased regional homogeneity (ReHo) in the right cerebellum and right superior occipital lobes (FWE-corrected p < 0.05), which negatively correlated with Y-BOCS scores (p < 0.05). Furthermore, cerebellar ALFF negatively correlated with the CTQ emotional abuse subscale (r = - 0.514, p < 0.01). Mediation analysis revealed that cerebellar ALFF mediated the relationship between CTQ-emotional abuse and Y-BOCS (good model fit: R2 = 0.231, MSE = 14.311, F = 5.721, p < 0.01; direct effect, c' = 0.153, indirect effect, a*b = 0.191). Findings indicated abnormal spontaneous and regional cerebellar activity in OCD, suggesting childhood trauma impacts OCD symptoms through cerebellar neural remodeling, highlighting its importance for clinical treatment selection.

Resting-state functional connectivity of amygdala subregions across different symptom subtypes of obsessive-compulsive disorder patients.

AIM: Obsessive-compulsive disorder (OCD) is a heterogeneous condition characterized by distinct symptom subtypes, each with varying pathophysiologies and treatment responses. Recent research has highlighted the role of the amygdala, a brain region that is central to emotion processing, in these variations. However, the role of amygdala subregions with distinct functions has not yet been fully elucidated. In this study, we aimed to clarify the biological mechanisms underlying OCD subtype heterogeneity by investigating the functional connectivity (FC) of amygdala subregions across distinct OCD symptom subtypes. METHODS: Resting-state functional magnetic resonance images were obtained from 107 medication-free OCD patients and 110 healthy controls (HCs). Using centromedial, basolateral, and superficial subregions of the bilateral amygdala as seed regions, whole-brain FC was compared between OCD patients and HCs and among patients with different OCD symptom subtypes, which included contamination fear and washing, obsessive (i.e., harm due to injury, aggression, sexual, and religious), and compulsive (i.e., symmetry, ordering, counting, and checking) subtypes. RESULTS: Compared to HCs, compulsive-type OCD patients exhibited hypoconnectivity between the left centromedial amygdala (CMA) and bilateral superior frontal gyri. Compared with patients with contamination fear and washing OCD subtypes, patients with compulsive-type OCD showed hypoconnectivity between the left CMA and left frontal cortex. CONCLUSIONS: CMA-frontal cortex hypoconnectivity may contribute to the compulsive presentation of OCD through impaired control of behavioral responses to negative emotions. Our findings underscored the potential significance of the distinct neural underpinnings of different OCD manifestations, which could pave the way for more targeted treatment strategies in the future.

Identifying subgroups of urge suppression in Obsessive-Compulsive Disorder using machine learning.

Obsessive-compulsive disorder (OCD) is phenomenologically heterogeneous. While predominant models suggest fear and harm prevention drive compulsions, many patients also experience uncomfortable sensory-based urges ("sensory phenomena") that may be associated with heightened interoceptive sensitivity. Using an urge-to-blink eyeblink suppression paradigm to model sensory-based urges, we previously found that OCD patients as a group had more eyeblink suppression failures and greater activation of sensorimotor-interoceptive regions than controls. However, conventional approaches assuming OCD homogeneity may obscure important within-group variability, impeding precision treatment development. This study investigated the heterogeneity of urge suppression failure in OCD and examined relationships with clinical characteristics and neural activation. Eighty-two patients with OCD and 38 controls underwent an fMRI task presenting 60-s blocks of eyeblink suppression alternating with free-blinking blocks. Latent profile analysis identified OCD subgroups based on number of erroneous blinks during suppression. Subgroups were compared on behavior, clinical characteristics, and brain activation during task. Three patient subgroups were identified. Despite similar overall OCD severity, the subgroup with the most erroneous eyeblinks had the highest sensory phenomena severity, interoceptive sensitivity, and subjective urge intensity. Compared to other subgroups, this subgroup exhibited more neural activity in somatosensory and interoceptive regions during the early phase (first 30 s) of blink suppression and reduced activity in the middle frontal gyrus during the late phase (second 30 s) as the suppression period elapsed. Heterogeneity of urge suppression in OCD was associated with clinical characteristics and brain function. Our results reveal potential treatment targets that could inform personalized medicine.

Abnormal functional connectivity of the putamen in obsessive-compulsive disorder.

The putamen has been proposed to play a critical role in the development of obsessive-compulsive disorder (OCD). The primary objective of this study was to examine the resting-state regional activity and functional connectivity patterns of the putamen in individuals diagnosed with OCD. To achieve this, we employed resting-state functional magnetic resonance imaging (rs-fMRI) to collect data from a sample of 45 OCD patients and 53 healthy control participants. We aimed to use the regional amplitude of low-frequency fluctuation (ALFF) analysis to generate the ROI masks of the putamen and then conduct the whole brain functional connectivity of the putamen in individuals with OCD. Compared to controls, the OCD group demonstrated decreased ALFF in bilateral putamen. The right putamen also displayed decreased FC with the left putamen extending to the inferior frontal gyrus (IFG), bilateral precuneus extending to calcarine, the right middle occipital cortex extending to the right middle temporal cortex, and the left middle occipital gyrus. The decreased connectivity between the right putamen and the left IFG was negatively correlated with Yale-Brown Obsessive Compulsive scale (Y-BOCS) Obsession Scores. This study aimed to reveal the putamen changes in resting-state activity and connectivity in OCD patients, highlighting the significance of aberrant ALFF/FC of the putamen is a key characteristic of OCD.

Abnormalities in static and dynamic intrinsic neural activity and neurotransmitters in first-episode OCD.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling disorder in which the temporal variability of regional brain connectivity is not well understood. The aim of this study was to investigate alterations in static and dynamic intrinsic neural activity (INA) in first-episode OCD and whether these changes have the potential to reflect neurotransmitters. METHODS: A total of 95 first-episode OCD patients and 106 matched healthy controls (HCs) were included in this study. Based on resting-state functional magnetic resonance imaging (rs-fMRI), the static and dynamic local connectivity coherence (calculated by static and dynamic regional homogeneity, sReHo and dReHo) were compared between the two groups. Furthermore, correlations between abnormal INA and PET- and SPECT-derived maps were performed to examine specific neurotransmitter system changes underlying INA abnormalities in OCD. RESULTS: Compared with HCs, OCD showed decreased sReHo and dReHo values in left superior, middle temporal gyrus (STG/MTG), left Heschl gyrus (HES), left putamen, left insula, bilateral paracentral lobular (PCL), right postcentral gyrus (PoCG), right precentral gyrus (PreCG), left precuneus and right supplementary motor area (SMA). Decreased dReHo values were also found in left PoCG, left PreCG, left SMA and left middle cingulate cortex (MCC). Meanwhile, alterations in INA present in brain regions were correlated with dopamine system (D2, FDOPA), norepinephrine transporter (NAT) and the vesicular acetylcholine transporter (VAChT) maps. CONCLUSION: Static and dynamic INA abnormalities exist in first-episode OCD, having the potential to reveal the molecular characteristics. The results help to further understand the pathophysiological mechanism and provide alternative therapeutic targets of OCD.

Cerebellar functional connectivity and its associated genes: A longitudinal study in drug-naive patients with obsessive-compulsive disorder.

The role of cerebellar-cerebral functional connectivity (CC-FC) in obsessive-compulsive disorder (OCD), its trajectory post-pharmacotherapy, and its potential as a prognostic biomarker and genetic mechanism remain uncertain. To address these gaps, this study included 37 drug-naive OCD patients and 37 healthy controls (HCs). Participants underwent baseline functional magnetic resonance imaging (fMRI), followed by four weeks of paroxetine treatment for patients with OCD, and another fMRI scan post-treatment. We examined seed-based CC-FC differences between the patients and HCs, and pre- and post-treatment patients. Support vector regression (SVR) based on CC-FC was performed to predict treatment response. Correlation analysis explored associations between CC-FC and clinical features, as well as gene profiles. Compared to HCs, drug-naive OCD patients exhibited reduced CC-FC in executive, affective-limbic, and sensorimotor networks, with specific genetic profiles associated with altered CC-FC. Gene enrichment analyses highlighted the involvement of these genes in various biological processes, molecular functions, and pathways. Post-treatment, the patients showed partial clinical improvement and partial restoration of the previously decreased CC-FC. Abnormal CC-FC at baseline correlated negatively with compulsions severity and social functional impairment, while changes in CC-FC correlated with cognitive function changes post-treatment. CC-FC emerged as a potential predictor of symptom severity in patients following paroxetine treatment. This longitudinal resting-state fMRI study underscores the crucial role of CC-FC in the neuropsychological mechanisms of OCD and its pharmacological treatment. Transcriptome-neuroimaging spatial correlation analyses provide insight into the neurobiological mechanisms underlying OCD pathology. Furthermore, SVR analyses hold promise for advancing precision medicine approaches in treating patients with OCD.

Investigating brain structure and tDCS response in obsessive-compulsive disorder.

Obsessive-Compulsive Disorder (OCD) is characterized by intrusive thoughts and repetitive behaviors, with associated brain abnormalities in various regions. This study explores the correlation between neural biomarkers and the response to transcranial Direct Current Stimulation (tDCS) in OCD patients. Using structural MRI data from two tDCS trials involving 55 OCD patients and 28 controls, cortical thickness, and gray matter morphometry was analyzed. Findings revealed thicker precentral and paracentral areas in OCD patients, compared to control (p < 0.001). Correlations between cortical thickness and treatment response indicated a significant association between a thinner precentral area and reduced Yale-Brown Obsessive Compulsive Scale (YBOCS) scores (p = 0.02). While results highlight the complexity of treatment response predictors, this study sheds light on potential neural markers for tDCS response in OCD patients. Further investigations with larger datasets are warranted to better understand the underpinnings of these biomarkers and their implications for personalized treatment approaches.

The impact of illness duration on brain activity in goal-directed and habit-learning systems in obsessive-compulsive disorder progression: A resting-state functional imaging study.

It is increasingly evident that structural and functional changes in brain regions associated with obsessive-compulsive disorder (OCD) are often related to the development of the disease. However, limited research has been conducted on how the progression of OCD may lead to an imbalance between goal-directed and habit-learning systems. This study employs resting-state functional imaging to examine the relationship between illness duration and abnormal brain function in goal-directed/habitual-learning systems. Demographic, clinical, and multimodal fMRI data were collected from participants. Our findings suggest that, compared to healthy controls, individuals with OCD exhibit abnormal brain functional indicators in both goal-directed and habit-learning brain regions, with a more pronounced reduction observed in the goal-directed regions. Additionally, abnormal brain activity is associated with illness duration, and the abnormalities observed in goal-directed regions are more effective in distinguishing different courses of OCD patients. Patients with different durations of OCD have functional abnormalities in the goal-directed and habitual-learning brain regions. There are differences in the degree of abnormality in different brain regions, and these abnormalities may disrupt the balance between goal-directed and habitual-learning systems, leading to increasing reliance on repetitive behaviors.

Comparative analysis of resting-state EEG functional connectivity in depression and obsessive-compulsive disorder.

Major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) are psychiatric disorders that often co-occur. We aimed to investigate whether their high comorbidity could be traced not only by clinical manifestations, but also at the level of functional brain activity. In this paper, we examined the differences in functional connectivity (FC) at the whole-brain level and within the default mode network (DMN). Resting-state EEG was obtained from 43 controls, 26 OCD patients, and 34 MDD patients. FC was analyzed between 68 cortical sources, and between-group differences in the 4-30 Hz range were assessed via the Network Based Statistic method. The strength of DMN intra-connectivity was compared between groups in the theta, alpha and beta frequency bands. A cluster of 67 connections distinguished the OCD, MDD and control groups. The majority of the connections, 8 of which correlated with depressive symptom severity, were found to be weaker in the clinical groups. Only 3 connections differed between the clinical groups, and one of them correlated with OCD severity. The DMN strength was reduced in the clinical groups in the alpha and beta bands. It can be concluded that the high comorbidity of OCD and MDD can be traced at the level of FC.

Effects of antidepressants on brain structure and function in patients with obsessive-compulsive disorder: A review of neuroimaging studies.

Obsessive-compulsive disorder (OCD) affects 2-3% of people worldwide. Although antidepressants are the standard pharmachological treatment of OCD, their effect on the brain of individuals with OCD has not yet been fully clarified. We conducted a systematic search on PubMed, Scopus, Embase, and Web of Science to explore the effects of antidepressants on neuroimaging findings in OCD. Thirteen neuroimaging investigations were included. After antidepressant treatment, structural magnetic resonance imaging studies suggested thalamic, amygdala, and pituitary volume changes in patients. In addition, the use of antidepressants was associated with alterations in diffusion tensor imaging metrics in the left striatum, the right midbrain, and the posterior thalamic radiation in the right parietal lobe. Finally, functional magnetic resonance imaging highlighted possible changes in the ventral striatum, frontal, and prefrontal cortex. The small number of included studies and sample sizes, short durations of follow-up, different antidepressants, variable regions of interest, and heterogeneous samples limit the robustness of the findings of the present review. In conclusion, our review suggests that antidepressant treatment is associated with brain changes in individuals with OCD, and these results may help to deepen our knowledge of the pathophysiology of OCD and the brain mechanisms underlying the effects of antidepressants.

Abnormal structure and function of white matter in obsessive-compulsive disorder.

BACKGROUND: Abnormal structure and function of gray matter (GM) have been discovered in the cortico-striatal-thalamic-cortical (CSTC) circuit in obsessive-compulsive disorder (OCD). The GM structure and function may be influenced by the structure and function of the white matter (WM). Therefore, it is crucial to explore the characteristics of WM in OCD. METHODS: Diffusion tensor imaging and resting-state functional magnetic resonance imaging data of 52 patients with OCD and 39 healthy controls (HCs) were collected. The tract-based spatial statistics, amplitude of low-frequency fluctuations (ALFF), and structural-functional coupling approaches were utilized to explore the WM structure and function. Furthermore, the relationship between the abnormal WM structure and function and clinical symptoms of OCD was investigated using Pearson's correlation. Support vector machine was performed to evaluate whether patients with OCD could be identified with the changed WM structure and function. RESULTS: Compared to HCs, the lower fractional anisotropy (FA) values of four clusters including the superior corona radiata, anterior corona radiata, right superior longitudinal fasciculus, corpus callosum, left posterior corona radiata, fornix, and the right anterior limb of internal capsule, reduced ALFF/FA ratio in the left anterior thalamic radiation (ATR), and the decreased functional connectivity between the left ATR and the left dorsal lateral prefrontal cortex within CSTC circuit at rest were observed in OCD. The decreased ALFF/FA ratio in the left ATR negatively correlated with Yale-Brown Obsessive-Compulsive Scale obsessive thinking scores and Hamilton Anxiety Rating Scale scores in OCD. Furthermore, the features that combined the abnormal WM structure and function performed best in distinguishing OCD from HCs with the appropriate accuracy (0.80), sensitivity (0.82), as well as specificity (0.80). CONCLUSION: Current research discovered changed WM structure and function in OCD. Furthermore, abnormal WM structural-functional coupling may lead to aberrant GM connectivity within the CSTC circuit at rest in OCD. TRIAL REGISTRATION: Study on the mechanism of brain network in obsessive-compulsive disorder with multi-model magnetic resonance imaging (ChiCTR-COC-17013301).

Altered neural anticipation of reward and loss but not receipt in adolescents with obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by persistent, unwanted thoughts and repetitive actions. Such repetitive thoughts and/or behaviors may be reinforced either by reducing anxiety or by avoiding a potential threat or harm, and thus may be rewarding to the individual. The possible involvement of the reward system in the symptomatology of OCD is supported by studies showing altered reward processing in reward-related regions, such as the ventral striatum (VS) and the orbitofrontal cortex (OFC), in adults with OCD. However, it is not clear whether this also applies to adolescents with OCD. METHODS: Using functional magnetic resonance imaging, two sessions were conducted focusing on the anticipation and receipt of monetary reward (1) or loss (2), each contrasted to a verbal (control) condition. In each session, adolescents with OCD (n1=31/n2=26) were compared with typically developing (TD) controls (n1=33/ n2=31), all aged 10-19 years, during the anticipation and feedback phase of an adapted Monetary Incentive Delay task. RESULTS: Data revealed a hyperactivation of the VS, but not the OFC, when anticipating both monetary reward and loss in the OCD compared to the TD group. CONCLUSIONS: These findings suggest that aberrant neural reward and loss processing in OCD is associated with greater motivation to gain or maintain a reward but not with the actual receipt. The greater degree of reward 'wanting' may contribute to adolescents with OCD repeating certain actions more and more frequently, which then become habits (i.e., OCD symptomatology).

Structural neuroimaging of skin-picking disorder.

BACKGROUND: Skin-picking disorder (SPD) is conceptualized as an obsessive-compulsive and related disorder (OCRD). Patients with SPD excessively manipulate their skin, which leads to skin lesions, psychological distress, and functional impairment. The neuroanatomical facets of this disorder are still poorly understood. METHODS: A total of 220 participants (123 patients with a primary diagnosis of SPD and 97 healthy controls; mean age = 30 years, 80% female) were recruited for a voxel-based morphometry (VBM) study. VBM data were compared between patients and controls, and between three SPD subgroups, each characterized by a distinct age of symptom onset (before puberty, during puberty, adulthood). RESULTS: Relative to the healthy comparison group, patients with SPD had significantly less grey matter volume (GMV) in regions of interest (ROIs: insula, orbitofrontal cortex, pallidum, cerebellum, supramarginal gyrus) and in the frontal pole and occipital regions (whole-brain findings). Early onset of symptoms (before puberty) was associated with elevated levels of focused skin-picking, in addition to less GMV in specific ROIs (insula, orbitofrontal cortex) as well as in paracingulate/ superior temporal regions (whole-brain findings). CONCLUSIONS: SPD-related reductions in GMV were identified in brain regions involved in interoception, emotion regulation, and motor control. This partially aligns with findings for OCD. The detection of different age-of-onset groups based on clinical as well as morphometric data points to the heterogeneity of the disorder and warrants further investigation.

Resting-state functional connectivity of amygdala subregions predicts treatment outcome for cognitive behavioral therapy in obsessive-compulsive disorder at a 4-month follow-up.

BACKGROUND: Cognitive behavioral therapy (CBT) is considered as the first-line treatment for obsessive-compulsive disorder (OCD). However, the underlying neural mechanisms through which CBT exerts its effects in OCD remain unclear. This study aims to investigate whether the improvement of clinical symptoms in OCD patients after CBT treatment is associated with changes in resting-state functional connectivity (FC) of the amygdala subregion, and whether these changes can be served as potential predictors of four-months treatment efficacy. METHODS: We collected resting-state functional magnetic resonance imaging (rs-fMRI) data from 57 OCD patients and 50 healthy subjects at baseline. In the patient group, rs-fMRI was also obtained after completion of an 8-week CBT treatment and 4 months post-treatment. A whole-brain rsFC analysis was conducted using the amygdala subregion as the seed point. We analyzed the FC patterns in relation to 4 months clinical outcomes to elucidate the long-term efficacy of CBT in OCD patients. RESULTS: Treatment responseat at pre-treatment was found to be associated with reduced rsFC between the left basolateral amygdala(BLA)and left superior temporal gyrus(STG) at baseline. Lower pre-treatment FC were negatively correlated with the severity of OCD symptoms as measured by the Yale-Brown Obsessive Compulsive Severity Scale (Y-BOCS). Moreover, the area under the receiver operating characteristic (ROC) curve for the FC between the left BLA and STG at the end of treatment was 73.0% and 70.4% for the effective-ineffective and remitted or unremitted groups, respectively. At the 4-month follow-up, the area under the ROC curve for the effective-ineffective and remitted or unremitted groups was 83.9% and 76.5%, respectively. CONCLUSION: These findings suggest that brain functional activity in patients with OCD can predict treatment response to CBT, and longitudinal changes in relevant brain functional activity following CBT treatment are associated with treatment response in OCD.

Neurocomputational model of compulsivity: deviating from an uncertain goal-directed system.

Despite a theory that an imbalance in goal-directed versus habitual systems serve as building blocks of compulsions, research has yet to delineate how this occurs during arbitration between the two systems in obsessive-compulsive disorder. Inspired by a brain model in which the inferior frontal cortex selectively gates the putamen to guide goal-directed or habitual actions, this study aimed to examine whether disruptions in the arbitration process via the fronto-striatal circuit would underlie imbalanced decision-making and compulsions in patients. Thirty patients with obsessive-compulsive disorder [mean (standard deviation) age = 26.93 (6.23) years, 12 females (40%)] and 30 healthy controls [mean (standard deviation) age = 24.97 (4.72) years, 17 females (57%)] underwent functional MRI scans while performing the two-step Markov decision task, which was designed to dissociate goal-directed behaviour from habitual behaviour. We employed a neurocomputational model to account for an uncertainty-based arbitration process, in which a prefrontal arbitrator (i.e. inferior frontal gyrus) allocates behavioural control to a more reliable strategy by selectively gating the putamen. We analysed group differences in the neural estimates of uncertainty of each strategy. We also compared the psychophysiological interaction effects of system preference (goal-directed versus habitual) on fronto-striatal coupling between groups. We examined the correlation between compulsivity score and the neural activity and connectivity involved in the arbitration process. The computational model captured the subjects' preferences between the strategies. Compared with healthy controls, patients had a stronger preference for the habitual system (t = -2.88, P = 0.006), which was attributed to a more uncertain goal-directed system (t = 2.72, P = 0.009). Before the allocation of controls, patients exhibited hypoactivity in the inferior frontal gyrus compared with healthy controls when this region tracked the inverse of uncertainty (i.e. reliability) of goal-directed behaviour (P = 0.001, family-wise error rate corrected). When reorienting behaviours to reach specific goals, patients exhibited weaker right ipsilateral ventrolateral prefronto-putamen coupling than healthy controls (P = 0.001, family-wise error rate corrected). This hypoconnectivity was correlated with more severe compulsivity (r = -0.57, P = 0.002). Our findings suggest that the attenuated top-down control of the putamen by the prefrontal arbitrator underlies compulsivity in obsessive-compulsive disorder. Enhancing fronto-striatal connectivity may be a potential neurotherapeutic approach for compulsivity and adaptive decision-making.

Reduced sleep quality defines a subtype of obsessive-compulsive disorder with lower Glx levels in the resting thalamus and worse response inhibition.

BACKGROUND: The aim of this study was to investigate the differences between resting and active thalamic neurometabolite levels and inhibitory function in obsessive compulsive disorder (OCD) patients with poor sleep quality (PSQ was defined as Pittsburgh Sleep Quality Index >5 and sleep efficiency ≤85%) compared to OCD patients with good sleep quality (GSQ) and healthy controls (HCs), as well as the relationship of these indices to obsessive compulsive symptoms. METHODS: Functional magnetic resonance spectroscopy (fMRS) was used to measure resting and active thalamic neurometabolite levels in 72 subjects (20 HCs and 38 OCD patients included in study analysis). Response inhibition function was measured by the Go-Nogo task before and during MRS recording. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The symptoms of OCD, anxiety and depression were evaluated using relevant clinical scales. RESULTS: OCD patients exhibited significantly reduced Glx/Cr levels in the resting thalamus. The levels of resting thalamic Glu/Cr and Glx/Cr in OCD patients with PSQ were significantly lowest. OCD patients had significantly lower correct rates on Go tasks, higher error rates on Nogo tasks, and longer error average response times (EART) to the Nogo task. OCD patients with PSQ demonstrated the highest Nogo task error rate and the longest EART to Nogo task. Furthermore, PSQI scores exhibited negative correlations with Glu/Cr and Glx/Cr in the resting thalamus. CONCLUSION: OCD patients with PSQ demonstrated reduced levels of thalamic resting Glx and more pronounced response inhibitory function impairment. Aberrant neurometabolite levels in critical brain regions, coupled with heightened response inhibition function deficits, may be a neurobiological basis for the PSQ that OCD patients generally exhibit.