Evolution of gamma knife capsulotomy for intractable obsessive-compulsive disorder.

For more than half a century, stereotactic neurosurgical procedures have been available to treat patients with severe, debilitating symptoms of obsessive-compulsive disorder (OCD) that have proven refractory to extensive, appropriate pharmacological, and psychological treatment. Although reliable predictors of outcome remain elusive, the establishment of narrower selection criteria for neurosurgical candidacy, together with a better understanding of the functional neuroanatomy implicated in OCD, has resulted in improved clinical efficacy for an array of ablative and non-ablative intervention techniques targeting the cingulum, internal capsule, and other limbic regions. It was against this backdrop that gamma knife capsulotomy (GKC) for OCD was developed. In this paper, we review the history of this stereotactic radiosurgical procedure, from its inception to recent advances. We perform a systematic review of the existing literature and also provide a narrative account of the evolution of the procedure, detailing how the procedure has changed over time, and has been shaped by forces of evidence and innovation. As the procedure has evolved and adverse events have decreased considerably, favorable response rates have remained attainable for approximately one-half to two-thirds of individuals treated at experienced centers. A reduction in obsessive-compulsive symptom severity may result not only from direct modulation of OCD neural pathways but also from enhanced efficacy of pharmacological and psychological therapies working in a synergistic fashion with GKC. Possible complications include frontal lobe edema and even the rare formation of delayed radionecrotic cysts. These adverse events have become much less common with new radiation dose and targeting strategies. Detailed neuropsychological assessments from recent studies suggest that cognitive function is not impaired, and in some domains may even improve following treatment. We conclude this review with discussions covering topics essential for further progress of this therapy, including suggestions for future trial design given the unique features of GKC therapy, considerations for optimizing stereotactic targeting and dose planning using biophysical models, and the use of advanced imaging techniques to understand circuitry and predict response. GKC, and in particular its modern variant, gamma ventral capsulotomy, continues to be a reliable treatment option for selected cases of otherwise highly refractory OCD.

Functional Segmentation of the Anterior Limb of the Internal Capsule: Linking White Matter Abnormalities to Specific Connections.

The anterior limb of the internal capsule (ALIC) carries thalamic and brainstem fibers from prefrontal cortical regions that are associated with different aspects of emotion, motivation, cognition processing, and decision-making. This large fiber bundle is abnormal in several psychiatric illnesses and a major target for deep brain stimulation. Yet, we have very little information about where specific prefrontal fibers travel within the bundle. Using a combination of tracing studies and diffusion MRI in male nonhuman primates, as well as diffusion MRI in male and female human subjects, we segmented the human ALIC into five regions based on the positions of axons from different cortical regions within the capsule. Fractional anisotropy (FA) abnormalities in patients with bipolar disorder were detected when FA was averaged in the ALIC segment that carries ventrolateral prefrontal cortical connections. Together, the results set the stage for linking abnormalities within the ALIC to specific connections and demonstrate the utility of applying connectivity profiles of large white matter bundles based on animal anatomic studies to human connections and associating disease abnormalities in those pathways with specific connections. The ability to functionally segment large white matter bundles into their components begins a new era of refining how we think about white matter organization and use that information in understanding abnormalities.SIGNIFICANCE STATEMENT The anterior limb of the internal capsule (ALIC) connects prefrontal cortex with the thalamus and brainstem and is abnormal in psychiatric illnesses. However, we know little about the location of specific prefrontal fibers within the bundle. Using a combination of animal tracing studies and diffusion MRI in animals and human subjects, we segmented the human ALIC into five regions based on the positions of axons from different cortical regions. We then demonstrated that differences in FA values between bipolar disorder patients and healthy control subjects were specific to a given segment. Together, the results set the stage for linking abnormalities within the ALIC to specific connections and for refining how we think about white matter organization in general.

Stop Signal Reaction Time Deficits in a Lifetime Obsessive-Compulsive Disorder Sample.

OBJECTIVES: Several studies have found impaired response inhibition, measured by a stop-signal task (SST), in individuals who are currently symptomatic for obsessive-compulsive disorder (OCD). The aim of this study was to assess stop-signal reaction time (SSRT) performance in individuals with a lifetime diagnosis of OCD, in comparison to a healthy control group. This is the first study that has examined OCD in participants along a continuum of OCD severity, including approximately half of whom had sub-syndromal symptoms at the time of assessment. METHODS: OCD participants were recruited primarily from within the OCD clinic at a psychiatric hospital, as well as from the community. Healthy controls were recruited from the community. We used the stop signal task to examine the difference between 21 OCD participants (mean age, 42.95 years) and 40 healthy controls (mean age, 35.13 years). We also investigated the relationship between SST and measures of OCD, depression, and anxiety severity. RESULTS: OCD participants were significantly slower than healthy controls with regard to mean SSRT. Contrary to our prediction, there was no correlation between SSRT and current levels of OCD, anxiety, and depression severity. CONCLUSIONS: Results support prior studies showing impaired response inhibition in OCD, and extend the findings to a sample of patients with lifetime OCD who were not all currently above threshold for diagnosis. These findings indicate that response inhibition deficits may be a biomarker of OCD, regardless of current severity levels. (JINS, 2016, 22, 785-789).

OCD behavior therapy before and after gamma ventral capsulotomy: case report.

We report the case of a patient requiring gamma ventral capsulotomy (GVC), a neurosurgical intervention to address severe refractory obsessive-compulsive disorder (OCD). GVC involves stereotactic lesions in the ventral anterior limb of the internal capsule and adjacent ventral striatum. This study details the course of an extinction-based behavioral therapy, namely exposure and response prevention (ERP). The patient experienced significant changes in motivation and ability to tolerate ERP post-surgery. Furthermore, he was better able to absorb and remember exposure sessions. GVC surgery may affect the neural mechanisms involved in the extinction learning process, the same process implicated in ERP treatment.

The persistent value of lesions in psychiatric neurosurgery.

Neurosurgery for intractable psychiatric conditions has seen a resurgence with the increasing use of deep brain stimulation (DBS). Although DBS promises reversible neuromodulation and has become more popular than older lesioning methods, lesioning might still be preferred in specific cases. Here, we review the evidence for DBS and lesions in the treatment of intractable neuropsychiatric conditions and consider the factors that favour the continued use of lesioning procedures in appropriately selected cases. Broadly, systemic factors including comparative effectiveness, cost, and ethical arguments support an ongoing role for lesioning. Such a role is also supported by practical considerations including patient experiences of this type of therapy, the relative intensity of follow-up care, access to sparse or specialised follow-up care, and relative infection risk. Overall, we argue that neurosurgical lesion procedures remain an important alternative to DBS and their continued availability is necessary to fulfil the imperatives of mental health parity and enhance access to effective mental health treatments. Nonetheless, the efficacy of DBS and recent advances in closed-loop stimulation and remote programming might provide solutions to some of the challenges associated with wider use of electrical neuromodulation. Concerns about the scarcity of high-level evidence for the efficacy of lesioning procedures as well as the potential irreversible adverse effects of lesioning remain to be addressed.

Childhood stress, gender, and cognitive control: Midline theta power.

The emergence of psychiatric symptoms is a common consequence of childhood stress exposure. However, there are a dearth of reliable clinical hallmarks or physiological biomarkers to predict post-trauma symptom emergence. The objective of this study was to examine if childhood stressors and stress-related symptoms are associated with altered midline theta power (MTP) during cognitive control demands, and how these associations interact with gender and early adversity. N = 53 children (ages 9-13 years old) from a longitudinal study of children maltreated during early childhood and non-maltreated children participated in this study. EEG recorded neural activity during a Zoo-Themed Go/No-Go task. Stress-related symptoms, recent stressful events, and other adversity experiences were identified. MTP was analyzed with clinical variables in a series of follow-up analyses. The number of stressors in the past six months was negatively correlated with MTP in those with low preschool adversity, but not in those with high preschool adversity. MTP was higher in girls than in boys, and the associations of MTP with stressors and symptoms were moderated by gender. MTP was negatively associated with stressors in the past six months in girls, while in boys, MTP was associated with stress-related symptoms. Childhood stressful events were associated with reduced MTP during cognitive control demands, and this was finding was moderated by gender and early life adversity. These preliminary findings suggest that boys and girls may process stressful experiences in distinct ways, and preschool adversity may potentially blunt the interaction between current stress and neural dynamics. However, ongoing investigation is needed.

Neurocysticercosis: Isolated Lesion in the Left Middle Frontal Gyrus.

OBJECTIVE: Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. We present a case study of a 21-year-old African man with an isolated NCC lesion to the left middle frontal gyrus, which is also known as the dorsolateral prefrontal cortex (dlPFC). METHOD: A neuropsychological evaluation was requested by the patient's inpatient psychiatry team regarding worsening attention and depressive symptoms approximately 6 months after NCC diagnosis and treatment. RESULTS: Neuropsychological findings revealed deficits in the aspects of executive functioning, attention, working memory, and significant depressive symptoms. CONCLUSION: To our knowledge, this is the first case study of its kind demonstrating deficits in cognitive functioning consistent with the dlPFC lesion location. Sociocultural and linguistic considerations, clinical findings, and limitations are discussed.

Predictors of Long-Term Exercise Engagement in Patients With Obsessive-Compulsive Disorder: The Role of Physical Activity Enjoyment.

Most U.S. adults, even more so those with psychiatric conditions like obsessive-compulsive disorder (OCD), do not engage in the recommended amount of physical activity (PA), despite the wide array of physical and mental health benefits associated with exercise. Therefore, it is essential to identify mechanistic factors that drive long-term exercise engagement so they can be targeted. Using the science of behavior change (SOBC) framework, this study examined potential predictors of long-term exercise engagement as a first step towards identifying modifiable mechanisms, in individuals with OCD, such as PA enjoyment, positive or negative affect, and behavioral activation. Fifty-six low-active patients (mean age = 38.8 ±â€¯13.0, 64% female) with a primary diagnosis of OCD were randomized to either aerobic exercise (AE; n = 28) or health education (HE; n = 28), and completed measures of exercise engagement, PA enjoyment, behavioral activation, and positive and negative affect at baseline, postintervention, and 3-, 6-, and 12-month follow-up. Significant predictors of long-term exercise engagement up to 6-months postintervention were baseline PA (Estimate = 0.29, 95%CI [0.09, 0.49], p = .005) and higher baseline PA enjoyment (Estimate = 1.09, 95%CI [0.30, 1.89], p = .008). Change in PA enjoyment from baseline to postintervention was greater in AE vs. HE, t(44) = -2.06, p = .046, d = -0.61, but endpoint PA enjoyment did not predict follow-up exercise engagement above and beyond baseline PA enjoyment. Other hypothesized potential mechanisms (baseline affect or behavioral activation) did not significantly predict exercise engagement. Results suggest that PA enjoyment may be an important modifiable target mechanism for intervention, even prior to a formal exercise intervention. Next steps aligned with the SOBC framework are discussed, including examining intervention strategies to target PA enjoyment, particularly among individuals with OCD or other psychiatric conditions, who may benefit most from long-term exercise engagement's effects on physical and mental health.

Understanding cingulotomy's therapeutic effect in OCD through computer models.

Cingulotomy is therapeutic in OCD, but what are the possible mechanisms? Computer models that formalize cortical OCD abnormalities and anterior cingulate cortex (ACC) function can help answer this. At the neural dynamics level, cortical dynamics in OCD have been modeled using attractor networks, where activity patterns resistant to change denote the inability to switch to new patterns, which can reflect inflexible thinking patterns or behaviors. From that perspective, cingulotomy might reduce the influence of difficult-to-escape ACC attractor dynamics on other cortical areas. At the functional level, computer formulations based on model-free reinforcement learning (RL) have been used to describe the multitude of phenomena ACC is involved in, such as tracking the timing of expected outcomes and estimating the cost of exerting cognitive control and effort. Different elements of model-free RL models of ACC could be affected by the inflexible cortical dynamics, making it challenging to update their values. An agent can also use a world model, a representation of how the states of the world change, to plan its actions, through model-based RL. OCD has been hypothesized to be driven by reduced certainty of how the brain's world model describes changes. Cingulotomy might improve such uncertainties about the world and one's actions, making it possible to trust the outcomes of these actions more and thus reduce the urge to collect more sensory information in the form of compulsions. Connecting the neural dynamics models with the functional formulations can provide new ways of understanding the role of ACC in OCD, with potential therapeutic insights.

Limitations of performance validity tests in dementia evaluations: The role of base rates.

Performance validity tests (PVTs) are frequently used to detect invalid performance on cognitive testing. The inclusion of PVTs in cognitive test batteries is commonplace irrespective of the condition of interest. However, base rates of invalid performance vary across clinical populations. Research accounting for base rates of invalid performance in varying clinical populations and PVT classification accuracy rates are not commonly synthesized. To address this gap, the present study examined the clinical utility of select PVTs used with older adults presenting for dementia evaluations. We computed posterior probabilities of invalid performance for the select PVTs using an estimated 5% base rate of invalid performance based on prior published studies. Posterior probabilities of invalid performance based on a PVT failure (i.e., invalid performance identified as invalid) ranged from 7.3% to 60.3% across PVTs; posterior probabilities of a false positive (i.e., valid performance identified as invalid) ranged from 39.7% to 92.7%. Conversely, posterior probabilities of a true negative (i.e., valid performance identified as valid) ranged from 95.7% to 99.3%; posterior probabilities of a false negative (i.e., invalid performance identified as valid) ranged from 0.7% to 4.3%. Results call into question the utility of PVTs in dementia evaluations. Consequently, the use of PVTs in dementia evaluations is likely to erroneously identify valid test data as invalid (i.e., false-positive error) at a frequency that exceeds the estimated 5% base rate of invalid performance. Further research examining correlates of invalid performance among older adults will clarify base rate estimates and potentially enhance the utility of PVTs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Patient Lived-Experience of Ventral Capsulotomy for Obsessive-Compulsive Disorder: An Interpretive Phenomenological Analysis of Neuroablative Psychiatric Neurosurgery.

Ventral Capsulotomy (VC) is a surgical intervention for treatment-resistant Obsessive-Compulsive Disorder (OCD). Despite clinical studies, little is known about patient perception and lived experience after neurosurgery for severe OCD. To examine the lived experiences of patients who have undergone VC for severe, treatment-resistant OCD through qualitative analysis. We conducted semi-structured interviews with six participants treated with VC for OCD. Interviews were analyzed using Interpretive Phenomenological Analysis. The following themes emerged: (1) After years of conventional treatments, patients felt neurosurgery was their "last hope" and described themselves as "desperate," (2) While some described the surgery as a "supernatural experience," patients also demonstrated understanding of the scientific procedure, its risks and potential benefits, (3) The surgical experience itself was positive or neutral, which was linked to trust in the clinical team, (4) Post-surgery, participants described months of heightened fear as they awaited lesion formation and functional improvement. (5) Patients consistently contextualized outcome in the context of their own life goals. Patients undergoing VC have positive views of this neurosurgical intervention, but psychiatric neurosurgical teams should anticipate patient discomfort with the time needed to achieve behavioral improvement following surgery and emphasize the importance of post-operative psychiatric care.

Differential assessment of frontally-mediated behaviors between self- and informant-report in patients with obsessive-compulsive disorder following gamma ventral capsulotomy.

Obsessive-Compulsive Disorder (OCD) is a debilitating disorder causing marked distress and functional impairment. While advances in behavioral and pharmacotherapies have been effective for a majority of patients with OCD, 10-30% remain treatment refractory and severely impaired. For a subset of treatment-resistant individuals with the most severe and disabling (intractable) illness, gamma ventral capsulotomy (GVC) appears effective in reducing OCD symptoms and functional impairment. However, the effects of the ventral internal capsule lesion via GVC surgery on executive function in everyday life have been minimally investigated. Examining behavioral outcomes of GVC also provides a rare opportunity to probe the functional importance of the ventral prefrontal-subcortical connections of the internal capsule white matter tract in a relatively homogenous sample of patients with comparable white matter lesions. The present study investigated changes in frontally-mediated behaviors, measured by the Frontal Systems Behavior Scale (FrSBe), following GVC in 45 individuals with severe and otherwise intractable OCD, as rated by patients themselves and family members. Linear mixed effects models revealed a significant improvement in patient self-ratings on the FrSBe after surgery, while family ratings did not significantly change. Interestingly, improvement on the FrSBe for both self and family raters was significantly correlated with improvement in OCD symptomatology post-surgery, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). At the group level, we found no evidence of decline in frontally-mediated behaviors assessed by the FrSBe as a result of focal white matter disconnection via GVC. However, we cannot rule out the possibility that placebo effects or compromised patient self-awareness or insight contributed to the significant improvement in self ratings. Our measures may also have limited sensitivity to more selective impairments that could result from a small lesion to the ventral internal capsule. The present study demonstrates the need for detailed investigation of cognitive and behavioral changes as important factors when considering GVC as a viable treatment option for patients with refractory OCD.

Patient-specific connectomic models correlate with, but do not reliably predict, outcomes in deep brain stimulation for obsessive-compulsive disorder.

Deep brain stimulation (DBS) of the ventral internal capsule/ventral striatum (VCVS) is an emerging treatment for obsessive-compulsive disorder (OCD). Recently, multiple studies using normative connectomes have correlated DBS outcomes to stimulation of specific white matter tracts. Those studies did not test whether these correlations are clinically predictive, and did not apply cross-validation approaches that are necessary for biomarker development. Further, they did not account for the possibility of systematic differences between DBS patients and the non-diagnosed controls used in normative connectomes. To address these gaps, we performed patient-specific diffusion imaging in 8 patients who underwent VCVS DBS for OCD. We delineated tracts connecting thalamus and subthalamic nucleus (STN) to prefrontal cortex via VCVS. We then calculated which tracts were likely activated by individual patients' DBS settings. We fit multiple statistical models to predict both OCD and depression outcomes from tract activation. We further attempted to predict hypomania, a VCVS DBS complication. We assessed all models' performance on held-out test sets. With this best-practices approach, no model predicted OCD response, depression response, or hypomania above chance. Coefficient inspection partly supported prior reports, in that capture of tracts projecting to cingulate cortex was associated with both YBOCS and MADRS response. In contrast to prior reports, however, tracts connected to STN were not reliably correlated with response. Thus, patient-specific imaging and a guideline-adherent analysis were unable to identify a tractographic target with sufficient effect size to drive clinical decision-making or predict individual outcomes. These findings suggest caution in interpreting the results of normative connectome studies.

Magnetic Resonance Imaging-Guided Laser Thermal Ventral Capsulotomy for Intractable Obsessive-Compulsive Disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling condition characterized by intrusive thoughts and repetitive behaviors. A subset of individuals have severe, treatment-resistant illness and are nonresponsive to medication or behavioral therapies. Without response to conventional therapeutic options, surgical intervention becomes an appropriate consideration. OBJECTIVE: To report clinical outcomes and the safety profile of bilateral ventral anterior capsulotomy for OCD using magnetic resonance (MR)-guided laser interstitial thermal therapy (LITT) in 10 patients followed for 6 to 24 mo. METHODS: A total of 10 patients underwent LITT for severe OCD; 1 patient withdrew prior to follow-up. LITT is a minimally invasive ablative technique performed with precise targeting and use of thermography under MR guidance. Lesions of the ventral anterior limb of the internal capsule by other techniques have been shown to be efficacious in prior studies. RESULTS: A total of 7 of the 9 patients were considered full responders (77.8%; Yale-Brown Obsessive-Compulsive Scale change ≥35%). Adverse effects included transient apathy/amotivation postsurgery (2 patients). One patient had a small tract hemorrhage where the laser fiber traversed the cerebral cortex as well as persistent insomnia postsurgery. One individual died after a drug overdose 7 mo postsurgery, which was judged unrelated to the surgery. CONCLUSION: LITT ventral capsulotomy was generally well tolerated, with promising evidence of effectiveness in the largest such series to date. Results were comparable to those after gamma knife ventral capsulotomy, as well as ventral anterior limb deep brain stimulation.

Double blind randomized controlled trial of deep brain stimulation for obsessive-compulsive disorder: Clinical trial design.

Obsessive-compulsive disorder (OCD), a leading cause of disability, affects ~1-2% of the population, and can be distressing and disabling. About 1/3 of individuals demonstrate poor responsiveness to conventional treatments. A small proportion of these individuals may be deep brain stimulation (DBS) candidates. Candidacy is assessed through a multidisciplinary process including assessment of illness severity, chronicity, and functional impact. Optimization failure, despite multiple treatments, is critical during screening. Few patients nationwide are eligible for OCD DBS and thus a multi-center approach was necessary to obtain adequate sample size. The study was conducted over a six-year period and was a NIH-funded, eight-center sham-controlled trial of DBS targeting the ventral capsule/ventral striatum (VC/VS) region. There were 269 individuals who initially contacted the sites, in order to achieve 27 participants enrolled. Study enrollment required extensive review for eligibility, which was overseen by an independent advisory board. Disabling OCD had to be persistent for ≥5 years despite exhaustive medication and behavioral treatment. The final cohort was derived from a detailed consent process that included consent monitoring. Mean illness duration was 27.2 years. OCD symptom subtypes and psychiatric comorbidities varied, but all had severe disability with impaired quality of life and functioning. Participants were randomized to receive sham or active DBS for three months. Following this period, all participants received active DBS. Treatment assignment was masked to participants and raters and assessments were blinded. The final sample was consistent in demographic characteristics and clinical features when compared to other contemporary published prospective studies of OCD DBS. We report the clinical trial design, methods, and general demographics of this OCD DBS sample.

The Severe Impairment Battery predicts functional abilities in an inpatient geriatric population.

There is limited research examining the relationship between cognition in severe dementia and functional skills. The aim of the present study was to examine the relationship between the Severe Impairment Battery (SIB) and functional abilities as measured by the Assessment of Instrumental Function (AIF) in an acute inpatient geriatric psychiatry setting. Analyses showed significant correlation between the SIB and the AIF. Multiple regression demonstrated that SIB scores accounted for 44% of the variance in adaptive functioning. These results replicate some of the prior data examining the relationship between the cognition and functional abilities and extend these findings into the inpatient setting with more severely impaired patients.

Neuropsychological features of delusions in hospitalized older adults with neurocognitive disorders.

Individuals with neurocognitive disorders (NCD) frequently experience psychotic symptoms, such as delusions. Delusions can contribute to other behavior problems, create dangers for patients and caregivers, and contribute to inpatient hospitalization of individuals with NCD. The current study aimed to identify cognitive symptoms associated with the presence of delusions and to differentiate delusion types based on cognitive profiles among hospitalized older adults with NCD. A review of electronic medical records of hospitalized older adults from an inpatient geriatric psychiatry setting yielded 185 patients with a diagnosis of mild or major NCD who had a neuropsychological evaluation during their admission and whose documentation described a clear delusion. We identified a comparison group of 185 patients without delusions well matched for age, education, and sex, and similar in global cognitive status. Exclusion criteria included delirium and history of a psychotic disorder. We first compared the groups' performances on a dementia battery. Then, cognitive performances of subgroups with specific delusion types (harm, theft, jealousy, and misidentification) were each compared to the remainder of the delusion-positive group. Exploratory analyses revealed that the delusion-positive group had a greater rate of discontinuation on Trails B and performed worse than the delusion-negative group on Trails A, Behavioral Dyscontrol Scale, Semantic Fluency, and Hopkins Verbal Learning Test-Revised (HVLT-R) initial registration. Theft delusions were associated with worse performance on HVLT-R recognition, misidentification delusions were associated with worse performance on Trails B, and harm delusions were associated with worse performance on a verbal generativity test. The presence of delusions in hospitalized older adults with NCD was associated with worse performance on several cognitive tasks with many being suggestive of associated with frontal-subcortical network integrity. Delusions of theft may be a consequence of reduced integrity of medial temporal lobe memory system.

Exploring response inhibition and error monitoring in obsessive-compulsive disorder.

Behavioral evidence of impaired response inhibition (RI) and hyperactive error monitoring (EM) in obsessive-compulsive disorder (OCD) is inconsistent. Recent neuroimaging work suggests that EM plays a role in RI impairments in OCD, but this has rarely been investigated using behavioral measures. The aims of this study were to (1) compare RI and EM performance between adults with OCD and non-psychiatric controls (NPC) while investigating possible moderators, and (2) assess whether excessive EM influences RI in OCD. We compared RI and EM performance on the Stop-Signal Task (SST) between 92 adults with OCD and 65 NPC from two Brazilian sites. We used linear regression to investigate which variables (group, age, medication use, clinical symptomatology) influenced performance, as well as to examine possible associations between RI and EM. OCD and NPC did not differ in RI and EM. However, age moderated RI performance in OCD with a medium effect size, reflecting differential effects of age on RI between groups: age was positively associated with RI in OCD but not NPC. Further, OCD severity predicted EM with a medium to large effect size, suggesting that more symptomatic patients showed greater monitoring of their mistakes. Finally, group moderated the relationship between RI and EM with a small effect size. Our findings suggest that demographic factors may influence RI, whereas clinical factors may influence EM. Further, we found preliminary behavioral evidence to indicate that impaired RI and excessive EM are related in OCD.

Comparison of the Association Between Goal-Directed Planning and Self-reported Compulsivity vs Obsessive-Compulsive Disorder Diagnosis.

Importance: Dimensional definitions of transdiagnostic mental health problems have been suggested as an alternative to categorical diagnoses, having the advantage of capturing heterogeneity within diagnostic categories and similarity across them and bridging more naturally psychological and neural substrates. Objective: To examine whether a self-reported compulsivity dimension has a stronger association with goal-directed and related higher-order cognitive deficits compared with a diagnosis of obsessive-compulsive disorder (OCD). Design, Setting, and Participants: In this cross-sectional study, patients with OCD and/or generalized anxiety disorder (GAD) from across the United States completed a telephone-based diagnostic interview by a trained rater, internet-based cognitive testing, and self-reported clinical assessments from October 8, 2015, to October 1, 2017. Follow-up data were collected to test for replicability. Main Outcomes and Measures: Performance was measured on a test of goal-directed planning and cognitive flexibility (Wisconsin Card Sorting Test [WCST]) and a test of abstract reasoning. Clinical variables included DSM-5 diagnosis of OCD and GAD and 3 psychiatric symptom dimensions (general distress, compulsivity, and obsessionality) derived from a factor analysis. Results: Of 285 individuals in the analysis (mean [SD] age, 32 [12] years; age range, 18-77 years; 219 [76.8%] female), 111 had OCD; 82, GAD; and 92, OCD and GAD. A diagnosis of OCD was not associated with goal-directed performance compared with GAD at baseline (ß [SE], -0.02 [0.02]; P = .18). In contrast, a compulsivity dimension was negatively associated with goal-directed performance (ß [SE], -0.05 [0.02]; P = .003). Results for abstract reasoning task and WCST mirrored this pattern; the compulsivity dimension was associated with abstract reasoning (ß [SE], 2.99 [0.63]; P < .001) and several indicators of WCST performance (eg, categories completed: ß [SE], -0.57 [0.09]; P < .001), whereas OCD diagnosis was not (abstract reasoning: ß [SE], 0.39 [0.66]; P = .56; categories completed: ß [SE], -0.09 [0.10]; P = .38). Other symptom dimensions relevant to OCD, obsessionality, and general distress had no reliable association with goal-directed performance, WCST, or abstract reasoning. Obsessionality had a positive association with requiring more trials to reach the first category on the WCST at baseline (ß [SE], 2.92 [1.39]; P = .04), and general distress was associated with impaired goal-directed performance at baseline (ß [SE],-0.04 [0.02]; P = .01). However, unlike the key results of this study, neither survived correction for multiple comparisons or was replicated at follow-up testing. Conclusions and Relevance: Deficits in goal-directed planning in OCD may be more strongly associated with a compulsivity dimension than with OCD diagnosis. This result may have implications for research assessing the association between brain mechanisms and clinical manifestations and for understanding the structure of mental illness.