High Prevalence of Psychological Comorbidities and Functional Neurological Symptoms in Women With Urinary Retention.

PURPOSE: Chronic idiopathic urinary retention (CIUR) in young women is poorly understood and a probable etiology is established only in around 40%, most commonly a primary disorder of external urethral sphincter relaxation, sometimes referred to as Fowler's syndrome. A high prevalence of psychological and functional comorbidities is reported, however these have been poorly characterized. MATERIALS AND METHODS: Women consecutively referred for the assessment and management of CIUR were evaluated cross-sectionally for 13 psychological/behavioral domains using a structured clinical interview: depression, anxiety, post-traumatic stress disorder (PTSD), other psychiatric history, functional neurological disorder, other functional syndromes, childhood and adult trauma, personality disorder, and self-harm (ever/current). RESULTS: A total of 91 women (mean age [SD]: 34 [11] years) were evaluated. Women with Fowler's syndrome (n = 69) were younger (mean age [SD]: 32 [9] vs 40 [13] years) than women without Fowler's syndrome and reported shorter mean duration of urinary symptoms (mean [SD]: 5 [6] vs 10 [9]). A high prevalence of psychiatric and psychological comorbidities was reported (97%) including current depression (77%), current anxiety (78%), and PTSD (32%). A high prevalence of functional neurological disorder (56%) and other functional symptoms (65%) was also reported. Self-harm was reported in (14%) and personality disorder in 16%. Childhood trauma was reported in 35% of women. CONCLUSIONS: Young women with CIUR report a high burden of psychiatric disorders, affective symptoms, trauma, PTSD, self-harm, and functional neurological disorder, particularly in those with Fowler's syndrome. These factors can undermine the engagement with health care professionals and affect management and should therefore be addressed during the urological assessment.

Functional neurological disorder is a feminist issue.

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.

Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers.

BACKGROUND: Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation. METHOD: 161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α. RESULTS: Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls. CONCLUSIONS: The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).

Inflammatory subgroups of schizophrenia and their association with brain structure: A semi-supervised machine learning examination of heterogeneity.

OBJECTIVE: Immune system dysfunction is hypothesised to contribute to structural brain changes through aberrant synaptic pruning in schizophrenia. However, evidence is mixed and there is a lack of evidence of inflammation and its effect on grey matter volume (GMV) in patients. We hypothesised that inflammatory subgroups can be identified and that the subgroups will show distinct neuroanatomical and neurocognitive profiles. METHODS: The total sample consisted of 1067 participants (chronic patients with schizophrenia n = 467 and healthy controls (HCs) n = 600) from the Australia Schizophrenia Research Bank (ASRB) dataset, together with 218 recent-onset patients with schizophrenia from the external Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism (BeneMin) dataset. HYDRA (HeterogeneitY through DiscRiminant Analysis) was used to separate schizophrenia from HC and define disease-related subgroups based on inflammatory markers. Voxel-based morphometry and inferential statistics were used to explore GMV alterations and neurocognitive deficits in these subgroups. RESULTS: An optimal clustering solution revealed five main schizophrenia groups separable from HC: Low Inflammation, Elevated CRP, Elevated IL-6/IL-8, Elevated IFN-γ, and Elevated IL-10 with an adjusted Rand index of 0.573. When compared with the healthy controls, the IL-6/IL-8 cluster showed the most widespread, including the anterior cingulate, GMV reduction. The IFN-γ inflammation cluster showed the least GMV reduction and impairment of cognitive performance. The CRP and the Low Inflammation clusters dominated in the younger external dataset. CONCLUSIONS: Inflammation in schizophrenia may not be merely a case of low vs high, but rather there are pluripotent, heterogeneous mechanisms at play which could be reliably identified based on accessible, peripheral measures. This could inform the successful development of targeted interventions.

Disrupted reward processing in Parkinson's disease and its relationship with dopamine state and neuropsychiatric syndromes: a systematic review and meta-analysis.

BACKGROUND: Neuropsychiatric symptoms are common in Parkinson's disease (PD) and predict poorer outcomes. Reward processing dysfunction is a candidate mechanism for the development of psychiatric symptoms including depression and impulse control disorders (ICDs). We aimed to determine whether reward processing is impaired in PD and its relationship with neuropsychiatric syndromes and dopamine replacement therapy. METHODS: The Ovid MEDLINE/PubMed, Embase and PsycInfo databases were searched for articles published up to 5 November 2020. Studies reporting reward processing task performance by patients with PD and healthy controls were included. Summary statistics comparing reward processing between groups were converted to standardised mean difference (SMD) scores and meta-analysed using a random effects model. RESULTS: We identified 55 studies containing 2578 participants (1638 PD and 940 healthy controls). Studies assessing three subcomponent categories of reward processing tasks were included: option valuation (n=12), reinforcement learning (n=37) and reward response vigour (n=6). Across all studies, patients with PD on medication exhibited a small-to-medium impairment versus healthy controls (SMD=0.34; 95% CI 0.14 to 0.53), with greater impairments observed off dopaminergic medication in within-subjects designs (SMD=0.43, 95% CI 0.29 to 0.57). Within-subjects subcomponent analysis revealed impaired processing off medication on option valuation (SMD=0.57, 95% CI 0.39 to 0.75) and reward response vigour (SMD=0.36, 95% CI 0.13 to 0.59) tasks. However, the opposite applied for reinforcement learning, which relative to healthy controls was impaired on-medication (SMD=0.45, 95% CI 0.25 to 0.65) but not off-medication (SMD=0.28, 95% CI -0.03 to 0.59). ICD was the only neuropsychiatric syndrome with sufficient studies (n=13) for meta-analysis, but no significant impairment was identified compared tonon-ICD patients (SMD=-0.02, 95% CI -0.43 to 0.39). CONCLUSION: Reward processing disruption in PD differs according to subcomponent and dopamine medication state, and warrants further study as a potential treatment target and mechanism underlying associated neuropsychiatric syndromes.

The organisational climate of NHS Early Intervention Services (EIS) for psychosis: a qualitative analysis.

BACKGROUND: Cognitive remediation (CR) therapy for psychosis significantly improves recovery but is yet to be widely implemented in NHS services. It is likely to be of value at the earliest stages of psychosis development - at the first episode. Organisational climate is one factor likely to affect implementation into Early Intervention Services (EIS), which serve those experiencing first episode psychosis. We aimed to understand the organisational climate within UK NHS Early Intervention for Psychosis (EIP) services and the barriers and facilitators for the introduction of CR. METHODS: We conducted semi structured interviews with 42 EIS members of four teams in four NHS Trusts. Thematic analysis was used to analyse the data. RESULTS: There were differences between teams, including leadership style, involvement in decision making and willingness to adopt CR. Resource shortages were considered the main barrier for implementation across all teams. The evidence base behind CR and the recognition of there being a clinical need was seen as the main facilitator. Teams with more democratic leadership, and knowledge of both the evidence base and need for CR, may feel better able to successfully incorporate it into their service. CONCLUSION: Despite enthusiasm for novel treatments, EIS teams are limited by their resources. An understanding of the local organisational variables can help teams establish a culture that values innovation. Clear communication of the evidence base for CR is key to help enable staff to implement novel treatments successfully despite these limited resources and time pressures.

Deconstructing depression and negative symptoms of schizophrenia; differential and longitudinal immune correlates, and response to minocycline treatment.

BACKGROUND: Immune dysfunction has been implicated in negative symptoms of schizophrenia and also in depression. These disorders are frequently co-morbid, with some symptoms such as anhedonia and apathy common to both. The anti-inflammatory agent minocycline may be ineffective in schizophrenia, but more positive effects have been seen in depression. Our aim was to investigate the role of immune dysfunction in depression and sub-domains of negative symptoms in schizophrenia by investigating their intercorrelation and the influence of treatment with minocycline. METHODS: We analysed longitudinal data from 207 patients within 5 years of onset of schizophrenia, from the randomised double-blind, placebo-controlled trial of minocycline (BeneMin). Symptom ratings and circulating IL-6, C-reactive protein (CRP) and TNF-α concentrations were collected at baseline and repeated over twelve months. The sample was not stratified by CRP prior to randomisation. Positive and Negative Syndrome Scale composite ratings of avolition-apathy and diminished expression, Calgary Depression Scale total scores, and immune markers were examined cross-sectionally using Spearman's rank, and longitudinally by linear mixed effect models that included body mass index and minocycline. Additionally, post hoc analysis of the sample stratified by elevated CRP (>1 mg/l and <10 mg/l at baseline) was carried out to assess whether minocycline had any effect on specific symptoms in an immune active sub-group of patients. RESULTS: Depression and avolition-apathy were significantly positively related, and depression correlated weakly with IL-6 at baseline. Diminished expression was associated with increased TNF-α both cross-sectionally and longitudinally. CRP was unrelated to any symptom domain. Minocycline did not affect any individual symptom or sub-domain in the full sample or in the immune active sub-group. DISCUSSION: IL-6 may have some specificity to depression in early schizophrenia. TNF-α may be an indicator of immune dysfunction relevant to negative symptoms, and our longitudinal findings add to this evidence. However, minocycline continues to show very little promise as a treatment for any symptom dimension of early schizophrenia.

Impaired automatic but intact volitional inhibition in primary tic disorders.

The defining character of tics is that they can be transiently suppressed by volitional effort of will, and at a behavioural level this has led to the concept that tics result from a failure of inhibition. However, this logic conflates the mechanism responsible for the production of tics with that used in suppressing them. Volitional inhibition of motor output could be increased to prevent the tic from reaching the threshold for expression, although this has been extensively investigated with conflicting results. Alternatively, automatic inhibition could prevent the initial excitation of the striatal tic focus-a hypothesis we have previously introduced. To reconcile these competing hypotheses, we examined different types of motor inhibition in a group of 19 patients with primary tic disorders and 15 healthy volunteers. We probed proactive and reactive inhibition using the conditional stop-signal task, and applied transcranial magnetic stimulation to the motor cortex, to assess movement preparation and execution. We assessed automatic motor inhibition with the masked priming task. We found that volitional movement preparation, execution and inhibition (proactive and reactive) were not impaired in tic disorders. We speculate that these mechanisms are recruited during volitional tic suppression, and that they prevent expression of the tic by inhibiting the nascent excitation released by the tic generator. In contrast, automatic inhibition was abnormal/impaired in patients with tic disorders. In the masked priming task, positive and negative compatibility effects were found for healthy controls, whereas patients with tics exhibited strong positive compatibility effects, but no negative compatibility effect indicative of impaired automatic inhibition. Patients also made more errors on the masked priming task than healthy control subjects and the types of errors were consistent with impaired automatic inhibition. Errors associated with impaired automatic inhibition were positively correlated with tic severity. We conclude that voluntary movement preparation/generation and volitional inhibition are normal in tic disorders, whereas automatic inhibition is impaired-a deficit that correlated with tic severity and thus may constitute a potential mechanism by which tics are generated.

A systematic review of the effects of psychiatric medications on social cognition.

INTRODUCTION: Social cognition is an important area of mental functioning relevant to psychiatric disorders and social functioning, that may be affected by psychiatric drug treatments. The aim of this review was to investigate the effects of medications with sedative properties, on social cognition. METHOD: This systematic review included experimental and neuroimaging studies investigating drug effects on social cognition. Data quality was assessed using a modified Downs and Black checklist (Trac et al. CMAJ 188: E120-E129, 2016). The review used narrative synthesis to analyse the data. RESULTS: 40 papers were identified for inclusion, 11 papers investigating benzodiazepine effects, and 29 investigating antipsychotic effects, on social cognition. Narrative synthesis showed that diazepam impairs healthy volunteer's emotion recognition, with supporting neuroimaging studies showing benzodiazepines attenuate amygdala activity. Studies of antipsychotic effects on social cognition gave variable results. However, many of these studies were in patients already taking medication, and potential practice effects were identified due to short-term follow-ups. CONCLUSION: Healthy volunteer studies suggest that diazepam reduces emotional processing ability. The effects of benzodiazepines on other aspects of social cognition, as well as the effects of antipsychotics, remain unclear. Interpretations of the papers in this review were limited by variability in measures, small sample sizes, and lack of randomisation. More robust studies are necessary to evaluate the impact of these medications on social cognition.

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population.

Voluntary tic suppression and the normalization of motor cortical beta power in Gilles de la Tourette syndrome: an EEG study.

Gilles de la Tourette syndrome (GTS) is a neurological condition characterized by motor and vocal tics. Previous studies suggested that this syndrome is associated with abnormal sensorimotor cortex activity at rest, as well as during the execution of voluntary movements. It has been hypothesized that this abnormality might be interpreted as a form of increased tonic inhibition, probably to suppress tics; however, this hypothesis has not been tested so far. The present study was designed to formally test how voluntary tic suppression in GTS influences the activity of the sensorimotor cortex during the execution of a motor task. We used EEG to record neural activity over the contralateral sensorimotor cortex during a finger movement task in adult GTS patients, in both free ticcing and tic suppression conditions; these data were then compared with those collected during the same task in age-matched healthy subjects. We focused on the levels of activity in the beta frequency band, which is typically associated with the activation of the motor system, during three different phases: a pre-movement, a movement, and a post-movement phase. GTS patients showed decreased levels of beta modulation with respect to the healthy controls, during the execution of the task; however, this abnormal pattern returned to be normal when they were explicitly asked to suppress their tics while moving. This is the first demonstration that voluntary tic suppression in GTS operates through the normalization of the EEG rhythm in the beta frequency range during the execution of a voluntary finger movement.

Customized breast cancer risk assessment in an ambulatory clinic: a portal for identifying women at risk.

PURPOSE: Existing high-risk clinic models focus on patients with known risk factors, potentially missing many high-risk patients. Here we describe our experience implementing universal risk assessment in an ambulatory breast center. METHODS: Since May 2017, all breast center patients completed a customized intake survey addressing known breast cancer risk factors and lifestyle choices. Patient characteristics, family history, risk scores, and lifestyle factors were examined; patients with high-risk breast lesions were excluded. Patients were considered at increased risk by model thresholds Gail 5-year risk > 1.7% (35-59 years), Gail 5-year risk > 5.5% (≥ 60 years), or Tyrer-Cuzick (T-C) v7 lifetime risk > 20% (any age). RESULTS: From May 2017-April 2018, there were 874 eligible patients-420 (48%) referred for risk assessment (RA) and 454 (52%) for non-specific breast complaints (NSBC). Overall, 389 (45%) were at increased risk of breast cancer. Gail 5-year risks were similar between RA and NSBC patients. However, RA patients more frequently met criteria by T-C score (P = 0.02). Of all patients at increased risk, 149 (39%) were overweight (BMI > 25) or obese (BMI > 30) and only 159 (41%) met recommended exercise standards. NSBC patients who met criteria were more frequently smokers (8% vs 1%, P < 0.01); all other demographic/lifestyle factors were similar among high-risk patients regardless of referral reason. CONCLUSIONS: Universal risk assessment in a comprehensive breast health center identified 45% of our population to be at increased risk of breast cancer. This clinical care model provides a unique opportunity to identify and address modifiable risk factors among women at risk.

Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study.

BACKGROUND: Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting. METHODS: We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases. RESULTS: Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi. CONCLUSION: The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.

Motor cortical excitability during voluntary inhibition of involuntary tic movements.

BACKGROUND: Tics can be voluntarily inhibited. However, the neurophysiology of voluntary tic inhibition remains underexplored. The objective of this study was to explore state-dependent effects of voluntary tic inhibition on M1 excitability. METHODS: Neurophysiological assessments (single motor-evoked potentials, corticospinal recruitment curves, short-interval intracortical inhibition, H-reflex) were performed in 14 adults with Tourette syndrome during voluntary tic inhibition and free ticcing. Regressions between behavioral performance and neurophysiological measures were also performed. RESULTS: Voluntary tic inhibition reduced corticospinal excitability: the greater the ability to inhibit tics, the greater was the reduction in excitability. Voluntary tic inhibition was not associated with changes in the excitability of short-interval intracortical inhibition or the H-reflex. CONCLUSIONS: Voluntary inhibition of tics reduces the excitability of corticospinal output. The pattern of neurophysiological findings is consistent with a withdrawal of excitation, but not with modulation of the inhibitory interneuronal mechanisms involved in short-interval intracortical inhibition. © 2018 International Parkinson and Movement Disorder Society.

Refining the Deep Brain Stimulation Target within the Limbic Globus Pallidus Internus for Tourette Syndrome.

BACKGROUND: Deep brain stimulation (DBS) in patients with severe, refractory Tourette syndrome (TS) has demonstrated promising but variable results thus far. The thalamus and anteromedial globus pallidus internus (amGPi) have been the most commonly stimulated sites within the cortico-striato thalamic circuit, but an optimal target is yet to be elucidated. OBJECTIVES: This study of 15 patients with long-term amGPi DBS for severe TS investigated whether a specific anatomical site within the amGPi correlated with optimal clinical outcome for the measures of tics, obsessive compulsive behaviour (OCB), and mood. METHODS: Validated clinical assessments were used to measure tics, OCB, quality of life, anxiety, and depression before DBS and at the latest follow-up (17-82 months). Electric field simulations were created for each patient using information on electrode location and individual stimulation parameters. A subsequent regression analysis correlated these patient-specific simulations to percentage changes in outcome measures in order to identify any significant voxels related to clinical improvement. RESULTS: A region within the ventral limbic GPi, specifically on the medial medullary lamina in the pallidum at the level of the AC-PC, was significantly associated with improved tics but not mood or OCB outcome. CONCLUSIONS: This study adds further support to the application of DBS in a tic-related network, though factors such as patient sample size and clinical heterogeneity remain as limitations and replication is required.

The role of alexithymia in the development of functional motor symptoms (conversion disorder).

BACKGROUND: The mechanisms leading to the development of functional motor symptoms (FMS) are of pathophysiological and clinical relevance, yet are poorly understood. AIM: The aim of the present study was to evaluate whether impaired emotional processing at the cognitive level (alexithymia) is present in patients affected by FMS. We conducted a cross-sectional study in a population of patients with FMS and in two control groups (patients with organic movement disorders (OMD) and healthy volunteers). METHODS: 55 patients with FMS, 33 patients affected by OMD and 34 healthy volunteers were recruited. The assessment included the 20-item Toronto Alexithymia Scale (TAS-20), the Montgomery-Asberg Depression Rating Scale, the Reading the Mind in the Eyes' Test and the Structured Clinical Interview for Personality Disorders. RESULTS: Alexithymia was present in 34.5% of patients with FMS, 9.1% with OMD and 5.9% of the healthy volunteers, which was significantly higher in the FMS group (χ(2) (2)=14.129, p<0.001), even after controlling for the severity of symptoms of depression. Group differences in mean scores were observed on both the difficulty identifying feelings and difficulty describing feelings dimensions of the TAS-20, whereas the externally orientated thinking subscale score was similar across the three groups. Regarding personality disorder, χ(2) analysis showed a significantly higher prominence of obsessive-compulsive personality disorder (OCPD) in the FMS group (χ(2) (2)=16.217, p<0.001) and 71.4% of those with OCPD also reached threshold criteria for alexithymia. CONCLUSIONS: Because alexithymia is a mental state denoting the inability to identify emotions at a cognitive level, one hypothesis is that some patients misattribute autonomic symptoms of anxiety, for example, tremor, paraesthesiae, paralysis, to that of a physical illness. Further work is required to understand the contribution of OCPD to the development of FMS.

Biofeedback treatment for Tourette syndrome: a preliminary randomized controlled trial.

OBJECTIVE: To study the clinical effectiveness of biofeedback treatment in reducing tics in patients with Tourette syndrome. BACKGROUND: Despite advances in the pharmacologic treatment of patients with Tourette syndrome, many remain troubled by their tics, which may be resistant to multiple medications at tolerable doses. Electrodermal biofeedback is a noninvasive biobehavioral intervention that can be useful in managing neuropsychiatric and neurologic conditions. METHODS: We conducted a randomized controlled trial of electrodermal biofeedback training in 21 patients with Tourette syndrome. RESULTS: After training the patients for 3 sessions a week over 4 weeks, we observed a significant reduction in tic frequency and improved indices of subjective well-being in both the active-biofeedback and sham-feedback (control) groups, but there was no difference between the groups in these measurements. Furthermore, the active-treatment group did not demonstrably learn to reduce their sympathetic electrodermal tone using biofeedback. CONCLUSIONS: Our findings indicate that this form of biofeedback training was unable to produce a clinical effect greater than placebo. The main confounding factor appeared to be the 30-minute duration of the training sessions, which made it difficult for patients to sustain a reduction in sympathetic tone when their tics themselves were generating competing phasic electrodermal arousal responses. Despite a negative finding in this study, electrodermal biofeedback training may have a role in managing tics if optimal training schedules can be identified.

Understanding the Mechanisms of Cognitive Remediation on Recovery in People With Early Psychosis: A Mediation and Moderation Analysis.

BACKGROUND: To provide precision cognitive remediation therapy (CR) for schizophrenia, we need to understand whether the mechanism for improved functioning is via cognition improvements. This mechanism has not been rigorously tested for potential moderator effects. STUDY DESIGN: We used data (n = 377) from a randomized controlled trial using CIRCuiTS, a therapist-supported CR, with participants from first-episode psychosis services. We applied structured equation modeling to test whether: (1) CR hours explain the goal attainment functional outcome (GAS) at posttreatment, (2) global cognitive improvement mediates GAS, and if (3) total symptoms moderate the CR hours to cognitive improvement pathway, and/or negative symptoms moderate the cognition to functioning pathway, testing moderator effects via the mediator or directly on CR hours to functioning path. STUDY RESULTS: CR produced significant functioning benefit for each therapy hour (Coeff = 0.203, 95% CI 0.101-0.304, P < .001). The mediated path from CR hours to cognition and cognition to functioning was small and nonsignificant (Coeff = 0.014, 95% CI = -0.010, 0.037, P = .256). Total symptoms did not moderate the path to cognition (P = .211) or the direct path to outcome (P = .896). However, negative symptoms significantly moderated the effect of cognitive improvements on functioning (P = .015) with high negative symptoms reducing the functional gains of improved cognition. CONCLUSIONS: Although cognitive improvements were correlated with functioning benefit, they did not fully explain the positive effect of increased therapy hours on functioning, suggesting additional CR factors also contribute to therapy benefit. Negative symptoms interfere with the translation of cognitive improvements into functional gains so need consideration.

Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation.

Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, the primary motor cortex in Tourette's syndrome, the supplementary motor area in Parkinson's disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairments in the human brain.