A worldwide study of white matter microstructural alterations in people living with Parkinson's disease.

The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20-89 years; 33% female) and 885 controls (age: 19-84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen's d effect sizes reached d = -1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.

Trauma-focused and personality disorder treatment for posttraumatic stress disorder and comorbid cluster C personality disorder: a randomized clinical trial.

Background: Posttraumatic stress disorder (PTSD) is associated with high rates of cluster C personality disorders (PD), which may negatively affect PTSD treatment. It is unknown whether concurrent treatment for PTSD and comorbid PD leads to superior treatment effects, compared to standard trauma-focused treatment.Objective: The objective was to test the efficacy of adding personality disorder treatment (group schema therapy; GST) to individual trauma-focused treatment (imagery rescripting; ImRs).Method: A two-arm randomized clinical trial (1:1 allocation ratio) was conducted between 2018 and 2023 at two sites of a mental health institution in the Netherlands. Raters were blind to treatment allocation. Adult outpatients with PTSD and comorbid cluster C personality disorders were randomized to receive either ImRs (12-18 sessions) or ImRs + GST (12-18 ImRs + 52-58 GST). The main outcome was PTSD severity one year after start of treatment measured with the Clinician-Administered PTSD Scale for DSM-5.Results: Of 130 patients (mean [SD] age = 40.6 [11.2], 110 [85%] females), 66 were assigned to ImRs and 64 to ImRs + GST. At 12 months, there were large decreases in PTSD severity (dImRs = 2.42, 95%CI = 1.97-2.87; dImRs + GST = 2.44, 95%CI = 1.99-2.90), but there was no significant difference between conditions (d = 0.02, 95%CI = -0.33-0.36, p = .944). Reductions in personality disorder symptoms and all other secondary outcomes were observed in both conditions. There were no significant differences between conditions on any of the secondary outcomes at 12 months.Conclusion: The more intensive concurrent trauma-focused and personality disorder treatment (ImRs + GST) was not superior to trauma-focused treatment alone (ImRs) for patients with PTSD and comorbid CPD. This suggests that trauma-focused treatment is the preferred primary treatment in patients presenting with both internalizing personality disorder and PTSD, reserving the stepping up to more intensive psychotherapy aimed at the personality disorder as a second line of treatment.Trial registration: ClinicalTrials.gov identifier: NCT03833531.

Concurrent trauma-focused and personality disorder treatment was not superior to only trauma-focused treatment for patients with posttraumatic stress disorder (PTSD) and comorbid cluster C personality disorders.Large reductions in PTSD severity and medium-to-large reductions in all secondary outcomes, including personality disorder symptoms, were observed in both treatment arms.These findings are remarkable, given the higher therapy dosage and specialized treatment for personality disorder comorbidity in the combined treatment arm.

TMS-induced plasticity improving cognitive control in OCD I: Clinical and neuroimaging outcomes from a randomised trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for obsessive-compulsive disorder (OCD). The neurobiological mechanisms of rTMS in OCD have been incompletely characterized. We compared clinical outcomes and changes in task-based brain activation following three different rTMS stimulation protocols, all combined with exposure and response prevention (ERP). METHODS: In this three-arm proof-of-concept randomized trial, 61 treatment-refractory adult OCD patients received 16 sessions of rTMS immediately prior to ERP over 8 weeks, with task-based functional MRI (tb-fMRI) scans and clinical assessments pre- and post-treatment. Patients received either: high frequency (HF) rTMS to the left dorsolateral prefrontal cortex (DLPFC)(n=19(6M/13F)); HF rTMS to the left pre-supplementary motor area (preSMA)(n=23(10M/13F)); or control rTMS to the vertex(n=19(6M/13F)). Changes in tb-fMRI activation pre-post treatment were compared using both a Bayesian region-of-interest and a general linear model whole-brain approach. RESULTS: Mean OCD symptom severity decreased significantly in all treatment groups (delta=-10.836, p<0.001, 95% CI[-12.504,-9.168]), with no differences between groups. Response rate in the entire sample was 57.4%. The DLPFC rTMS group showed decreased planning-related activation post-treatment that was associated with greater symptom improvement. No group-level activation changes were observed for the preSMA or vertex rTMS groups. Participants with greater symptom improvement in the preSMA group showed decreased error-related activation, and symptom improvement in the vertex group was associated with increased inhibition-related activation. CONCLUSIONS: PreSMA and DLPFC rTMS combined with ERP led to activation decreases in targeted task networks in individuals showing greater symptom improvement, although we observed no differences in symptom reduction between groups.

Targeted memory reactivation to augment treatment in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder with traumatic memories at its core. Post-treatment sleep may offer a unique time window to increase therapeutic efficacy through consolidation of therapeutically modified traumatic memories. Targeted memory reactivation (TMR) enhances memory consolidation by presenting reminder cues (e.g., sounds associated with a memory) during sleep. Here, we applied TMR in PTSD patients to strengthen therapeutic memories during sleep after one treatment session with eye movement desensitization and reprocessing (EMDR). PTSD patients received either slow oscillation (SO) phase-targeted TMR, using modeling-based closed-loop neurostimulation (M-CLNS) with EMDR clicks as a reactivation cue (n = 17), or sham stimulation (n = 16). Effects of TMR on sleep were assessed through high-density polysomnography. Effects on treatment outcome were assessed through subjective, autonomic, and fMRI responses to script-driven imagery (SDI) of the targeted traumatic memory and overall PTSD symptom level. Compared to sham stimulation, TMR led to stimulus-locked increases in SO and spindle dynamics, which correlated positively with PTSD symptom reduction in the TMR group. Given the role of SOs and spindles in memory consolidation, these findings suggest that TMR may have strengthened the consolidation of the EMDR-treatment memory. Clinically, TMR vs. sham stimulation resulted in a larger reduction of avoidance level during SDI. TMR did not disturb sleep or trigger nightmares. Together, these data provide first proof of principle that TMR may be a safe and viable future treatment augmentation strategy for PTSD. The required follow-up studies may implement multi-night TMR or TMR during REM sleep to further establish the clinical effect of TMR for traumatic memories.

Family planning decision-making in relation to psychiatric disorders in women: a qualitative focus group study.

BACKGROUND: Recent studies revealed an elevated likelihood of unintended pregnancies among women with psychiatric disorders compared to their counterparts without such vulnerability. Despite the importance of understanding family planning decision-making in this group, qualitative inquiries are lacking. This study explored family planning decisions among women with psychiatric disorders. METHODS: Utilizing a qualitative approach, three focus group discussions were conducted with purposive sampling: women with a history of unintended pregnancies (N = 3), women without children (N = 5), and women with a history of intended pregnancies (N = 9), all of whom had self-reported psychiatric disorders. Using thematic framework analysis, we investigated the themes "Shadow of the past," reflecting past experiences, and "Shadow of the future," reflecting future imaginaries, building upon the existing "Narrative Framework." RESULTS: The Narrative Framework formed the foundation for understanding family planning among women with psychiatric disorders. The retrospective dimension of focus group discussions provided opportunities for reflective narratives on sensitive topics, revealing emotions of regret, grief and relief. Childhood trauma, adverse events, and inadequate parenting enriched the "Shadow of the past". The "Shadow of the present" was identified as a novel theme, addressing awareness of psychiatric disorders and emotions toward psychiatric stability. Social influences, stigma, and concerns about transmitting psychiatric disorders shaped future imaginaries in the shadow of the future. CONCLUSIONS: This study enlightens how family planning decision-making in women with psychiatric disorders might be complex, as marked by the enduring impact of past experiences and societal influences in this sample. These nuanced insights underscore the necessity for tailored support for women with psychiatric disorders.

Recent studies show that women with psychiatric disorders are more likely to experience unintended pregnancies. However, the underlying reasons are not fully understood. Understanding those reasons is important to provide better healthcare. Our study explored how women with psychiatric disorders make decisions about family planning.We had conversations with different groups of women­women with unintended pregnancies, women without children, and women with intended pregnancies­through focus group discussions. We partnered with the Dutch mental health organization MIND to capture diverse opinions. Key themes and categories in the discussions were identified and organized.We found four main themes: "Shadow of the past" showed how past events, trauma, and lack of knowledge about parenting affect family planning. "Shadow of the present" revealed different feelings about family planning, the importance of the awareness of psychiatric disorders, and uncertainty about decisions. "Shadow of the future" included thoughts about becoming a mother, the impact of social influences, and concerns about passing on psychiatric disorders. "Reflections on the decision" showed how psychiatric disorders, experiences with motherhood, and feelings of regret, grief and relief had an influence on family planning decisions.In conclusion, our study highlighted the complexity of family planning decisions for women with psychiatric disorders. Past experiences and societal influences, like stigma, play a big role. These insights show the need for personalized family planning support for women with psychiatric disorders.

The conversation about family planning and desire for children in mental healthcare: Patients' perspective versus Professionals' perspective in a mixed methods study.

BACKGROUND: Reproductive health and mental health are intertwined, but studies investigating family planning needs and desire for children in mental healthcare are scarce. METHODS: We studied the experiences of (former) patients, those with close relationships with the (former) patients (close ones) and mental health professionals (MHP) on discussing family planning and desire for children in mental healthcare. We combined quantitative (two nationwide surveys) and qualitative data (four focus groups) in a mixed-methods approach with sequential analytical design. RESULTS: Combined data from focus groups (n = 19 participants) and two surveys (n = 139 MHPs and n = 294 (former) patients and close ones) showed that a considerable group of MHPs (64.0%), patients (40.9%) and close ones (50.0%) found that family planning should be discussed by a psychiatrist. However, several obstacles impeded a conversation, such as fear of judgment, lack of time and knowledge and limited opportunity for in-depth exploration of life themes in therapeutic relationships. CONCLUSIONS: To increase the autonomy of patients in discussing family planning, we suggest MHPs explore the desire to discuss family planning with all patients in the reproductive phase of life, prior to discussing contraceptive care. MHPs should receive education about psychiatric vulnerability in relation to family planning and desire for children, and patients and close ones should be empowered to initiate a conversation themselves.

Patient Perceptions of Illness Causes and Treatment Preferences for Obsessive-Compulsive Disorder: A Mixed-Methods Study.

Obsessive-compulsive disorder (OCD) is a condition with high patient morbidity and mortality. Research shows that eliciting patient explanations about illness causes and treatment preferences promotes cross-cultural work and engagement in health services. These topics are in the Cultural Formulation Interview (CFI), a semi-structured interview first published in DSM-5 that applies anthropological approaches within mental health services to promote person-centered care. This study focuses on the New York City site of an international multi-site study that used qualitative-quantitative mixed methods to: (1) analyze CFI transcripts with 55 adults with OCD to explore perceived illness causes and treatment preferences, and (2) explore whether past treatment experiences are related to perceptions about causes of current symptoms. The most commonly named causes were circumstantial stressors (n = 16), genetics (n = 12), personal psychological traits (n = 9), an interaction between circumstantial stressors and participants' brains (n = 6), and a non-specific brain problem (n = 6). The most common treatment preferences were psychotherapy (n = 42), anything (n = 4), nothing (n = 4), and medications (n = 2). Those with a prior medication history had twice the odds of reporting a biological cause, though this was not a statistically significant difference. Our findings suggest that providers should ask patients about illness causes and treatment preferences to guide treatment choice.

[Hitting and yelling during sleep: diagnosis and implications of REM sleep behavior disorder]. / Slaan en schreeuwen in de slaap.

Rapid eye movement (REM) sleep behavior disorder is characterized by dream enactment during REM sleep. Due to different treatment requirements, it is important to distinguish REM sleep behavior disorder from other causes of nocturnal restlessness, including sleep apnea, non-REM parasomnia and sleep-related hypermotor epilepsy. In addition, a diagnosis of isolated REM sleep behavior disorder is impactful, because it carries a greatly increased risk for the later development of Parkinson's disease and related synucleinopathies. In this clinical lesson we describe three patients with abnormal nocturnal movements and vocalizations. The history can provide important clues towards the diagnosis, but a video-polysomnography is required before REM sleep behavior disorder can be diagnosed.

Age of onset of obsessive-compulsive disorder differentially affects white matter microstructure.

Previous diffusion MRI studies have reported mixed findings on white matter microstructure alterations in obsessive-compulsive disorder (OCD), likely due to variation in demographic and clinical characteristics, scanning methods, and underpowered samples. The OCD global study was created across five international sites to overcome these challenges by harmonizing data collection to identify consistent brain signatures of OCD that are reproducible and generalizable. Single-shell diffusion measures (e.g., fractional anisotropy), multi-shell Neurite Orientation Dispersion and Density Imaging (NODDI) and fixel-based measures, were extracted from skeletonized white matter tracts in 260 medication-free adults with OCD and 252 healthy controls. We additionally performed structural connectome analysis. We compared cases with controls and cases with early (<18) versus late (18+) OCD onset using mixed-model and Bayesian multilevel analysis. Compared with healthy controls, adult OCD individuals showed higher fiber density in the sagittal stratum (B[SE] = 0.10[0.05], P = 0.04) and credible evidence for higher fiber density in several other tracts. When comparing early (n = 145) and late-onset (n = 114) cases, converging evidence showed lower integrity of the posterior thalamic radiation -particularly radial diffusivity (B[SE] = 0.28[0.12], P = 0.03)-and lower global efficiency of the structural connectome (B[SE] = 15.3[6.6], P = 0.03) in late-onset cases. Post-hoc analyses indicated divergent direction of effects of the two OCD groups compared to healthy controls. Age of OCD onset differentially affects the integrity of thalamo-parietal/occipital tracts and the efficiency of the structural brain network. These results lend further support for the role of the thalamus and its afferent fibers and visual attentional processes in the pathophysiology of OCD.

Long-term remission rates and trajectory predictors in obsessive-compulsive disorder: Findings from a six-year naturalistic longitudinal cohort study.

BACKGROUND: This naturalistic study, utilizing data from the Netherlands Obsessive-Compulsive Disorder Association (NOCDA) cohort, investigated the long-term remission rates and predictors of different trajectories of obsessive-compulsive disorder (OCD) within a clinical population. METHODS: A sample of 213 participants was classified into three illness trajectories: "Chronic," "Episodic, "and "Remitted-OCD." Long-term remission rates were calculated based on three follow-up measurements over a 6-year period. A multinomial logistic regression model, incorporating five selected predictors with high explanatory power and one covariate, was employed to analyze OCD trajectory outcomes. RESULTS: The long-term full remission rates, calculated from all the measurements combined (14%), were significantly lower than what was observed in earlier studies and when compared to assessments at each individual follow-up (∼30%). Moreover, high baseline symptom severity and early age of onset were identified as significant risk factors for a chronic course of OCD, while male sex and younger age predicted a more favorable trajectory. Notably, the likelihood of an episodic course remained high even without identified risk factors. LIMITATIONS: The bi-annual data collection process is unable to capture participants' clinical conditions between assessments. Additionally, no data was collected regarding the specific type and duration of psychological treatment received. Regarding the type of treatment participants received. CONCLUSIONS: Results suggest that long-term remission rates may be lower than previously reported. Consequently, employing multiple assessment points in longitudinal studies is necessary for valid estimation of long-term full remission rates. The results emphasize the importance of personalized clinical care and ongoing monitoring and maintenance for most OCD cases.

Pregnancy intention in relation to maternal and neonatal outcomes in women with versus without psychiatric diagnoses.

BACKGROUND: Studies have identified adverse maternal and neonatal outcomes for women with psychiatric disorders. Additionally, psychiatric disorders may pose an increased risk for unintended pregnancies (UPs) which in turn may also impact negatively on outcomes. The present study aims to compare the incidence of UPs in women with versus without current/past psychiatric diagnoses and investigates whether psychiatric history modifies the relation between delivery outcomes in women with and without UPs. METHODS: A retrospective cohort was compiled of women who gave birth in a large hospital in Amsterdam, the Netherlands. Women ≥18 years old with singleton pregnancies and birth registrations in the electronic patient file during January 1, 2015 to March 1, 2020 were included. Patient characteristics (including pregnancy intention and psychiatric history), maternal (gestational diabetes, mode of delivery) and neonatal outcomes (e.g., gestational age [GA], birthweight and Apgar scores) were registered by health care providers in hospital charts. Incidence of UPs was compared between women with versus without current/past psychiatric diagnoses. Maternal and neonatal outcomes were compared between women with versus without UPs with linear or logistic regression models adjusted for relevant confounders with an interaction term for UP with current/past psychiatric diagnoses. RESULTS: We included 1219 women with and 1093 women without current/past psychiatric diagnoses. Current/past psychiatric diagnoses were significantly associated with UPs after adjustment for confounders (39.0% vs. 29.6%, OR 1.56, CI 1.23-2.00, p < 0.001). In sub-analyses, women with depressive (OR 1.67, CI 1.24-2.26, p = 0.001), personality (OR 2.64, CI 1.38-5.11, p = 0.004) and substance-related and addictive disorders (OR 4.29, CI 1.90-10.03, p = 0.001) had higher odds of UPs compared to women without current/past psychiatric diagnoses. Amongst women with UPs, current/past psychiatric diagnoses did not modify maternal or neonatal outcomes, except for GA at delivery as women with both UPs and current/past psychiatric diagnosis had a 2.21-day higher mean GA at delivery than women in the reference group (p-value interaction = 0.001). CONCLUSIONS: Current/past psychiatric diagnoses are associated with a higher odd of UPs. In our sample, maternal and neonatal outcomes were comparable for women with and without UPs and these results were similar for women with and without current/past psychiatric diagnoses, except for GA at delivery. Although our study is limited by several factors, we found that women with current/past psychiatric diagnoses, irrespective of pregnancy planning status, do not have more adverse maternal or pregnancy outcomes. Increased efforts are needed to ensure that psychoeducation and conversations about pregnancy planning and UPs are available for women with current/past psychiatric diagnoses.

Repetitive Transcranial Magnetic Stimulation-Induced Neuroplasticity and the Treatment of Psychiatric Disorders: State of the Evidence and Future Opportunities.

Neuroplasticity, or activity-dependent neuronal change, is a crucial mechanism underlying the mechanisms of effect of many therapies for neuropsychiatric disorders, one of which is repetitive transcranial magnetic stimulation (rTMS). Understanding the neuroplastic effects of rTMS at different biological scales and on different timescales and how the effects at different scales interact with each other can help us understand the effects of rTMS in clinical populations and offers the potential to improve treatment outcomes. Several decades of research in the fields of neuroimaging and blood biomarkers is increasingly showing its clinical relevance, allowing measurement of the synaptic, functional, and structural changes involved in neuroplasticity in humans. In this narrative review, we describe the evidence for rTMS-induced neuroplasticity at multiple levels of the nervous system, with a focus on the treatment of psychiatric disorders. We also describe the relationship between neuroplasticity and clinical effects, discuss methods to optimize neuroplasticity, and identify future research opportunities in this area.

Changes in depression symptom profile with gender-affirming hormone use in transgender persons.

BACKGROUND: Women show higher prevalence of depression and different symptomatology than men, possibly influenced by sex hormones. Many transgender persons, who face a high risk of depression, use Gender-Affirming Hormone Therapy (GAHT), but the impact of GAHT on depressive symptom profiles is unknown. METHODS: This study examined depressive symptoms in transgender persons before GAHT and after 3- and 12 months of GAHT. We used the Inventory of Depressive Symptomatology-Self Report to assess depressive symptoms, exploratory factor analysis (EFA) to assess symptom clusters, and linear mixed models to assess changes in symptom clusters. RESULTS: This study included 110 transmasculine (TM) and 89 transfeminine (TF) participants. EFA revealed four symptom clusters: mood, anxiety, lethargy, and somatic symptoms. Changes in total depressive symptoms significantly differed between TM and TF groups. After 3 months of GAHT, TM participants reported improvement in lethargy (-16 %; 95%CI: -29 %; -2 %), and after 12 months TF participants reported worsening in low mood (24 %; 95%CI: 3 %; 51 %), but absolute score changes were modest. Neither group showed changes in anxiety or somatic symptoms. LIMITATIONS: This study had limited sample sizes at 12 months follow-up and did not include relevant biological or psychosocial covariates. DISCUSSION: Changes in depressive symptoms after GAHT use differ in TM and TF persons: TM persons report slight improvements in lethargy, whereas TF persons report a slight increase in low mood. Starting GAHT represents a significant life event with profound social and physical effects, and further research should assess social and biological effects of GAHT on mood-related symptoms.

Brain activation during an emotional task in participants with PTSD and borderline and/or cluster C personality disorders.

INTRODUCTION: Although comorbidity of post-traumatic stress disorder (PTSD) with borderline personality disorder (BPD) and/or cluster C personality disorders (CPD) is common, neural correlates of this comorbidity are unknown. METHODS: We acquired functional MRI scans during an emotional face task in participants with PTSD + CPD (n = 34), PTSD + BPD (n = 24), PTSD + BPD + CPD (n = 18) and controls (n = 30). We used ANCOVAs and Bayesian analyses on specific ROIs in a fearful vs. scrambled faces contrast. We also investigated associations with clinical measures. RESULTS: There were no robust differences in brain activation between the groups with ANCOVAs. Transdiagnostically, we found a negative association between severity of dissociation and right insula and right dmPFC activation, and emotion regulation problems with right dmPFC activation. Bayesian analyses showed credible evidence for higher activation in all ROIs in the PTSD + BPD + CPD group compared to PTSD + BPD and PTSD + CPD. DISCUSSION: Our Bayesian and correlation analyses support new dimensional conceptualizations of personality disorders.

Long-term effects of cognitive training in Parkinson's disease: A randomized, controlled trial.

Background: Computerized cognitive training may be promising to improve cognitive impairment in Parkinson's disease and has even been suggested to delay cognitive decline. However, evidence to date is limited. The aim of this study was to assess the durability of eight-week cognitive training effects at up to two years follow-up. Methods: One hundred and thirty-six (1 3 6) individuals with Parkinson's disease, subjective cognitive complaints but without severe cognitive impairment (Montreal Cognitive Assessment ≥ 22) participated in this double-blind RCT. Participants underwent an eight-week home-based intervention of either adaptive, computerized cognitive training with BrainGymmer (n = 68) or an active control (n = 68). They underwent extensive neuropsychological assessment, psychiatric questionnaires and motor symptom assessment at baseline and one and two years after the intervention. We used mixed-model analyses to assess changes in cognitive function at follow-up and performed Fisher's exact tests to assess conversion of cognitive status. Results: There were no group differences on any neuropsychological assessment outcome at one- and two-year follow-up. Groups were equally likely to show conversion of cognitive status at follow-up. A considerable amount of assessments was missed (1y: n = 27; 2y: n = 33), most notably due to COVID-19 regulations. Conclusions: Eight-week cognitive training did not affect long-term cognitive function in Parkinson's disease. Future studies may focus on one cognitive subgroup to enhance reliability of study results. Intervention improvements are needed to work towards effective, lasting treatment options.

TMS-induced plasticity improving cognitive control in OCD I: Clinical and neuroimaging outcomes from a randomised trial of rTMS for OCD.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment option for obsessive-compulsive disorder (OCD). The neurobiological mechanisms of rTMS in OCD have, however, been incompletely characterized. We compared clinical outcomes and changes in task-based brain activation following three different rTMS stimulation protocols, all combined with exposure and response prevention (ERP). Methods: In this three-arm proof-of-concept randomized controlled clinical trial, 61 treatment-refractory adult OCD patients received 16 sessions of rTMS immediately prior to ERP over 8 weeks, with task-based functional MRI (tb-fMRI) scans and clinical assessments pre- and post-treatment. Patients received either: high frequency (HF) rTMS to the left dorsolateral prefrontal cortex (DLPFC) (n=19 (6M/13F)); HF rTMS to the left pre-supplementary motor area (preSMA) (n=23 (10M/13F)); or control rTMS to the vertex (n=19 (6M/13F)). Changes in tb-fMRI activation pre-post treatment were compared using both a Bayesian region-of-interest and a general linear model whole-brain approach. Results: Mean OCD symptom severity decreased significantly in all treatment groups (delta=- 10.836, p<0.001, 95% CI [-12.504, -9.168]), with no differences between groups. Response rate in the entire sample was 57.4%. Groups receiving DLPFC or preSMA rTMS showed, respectively, a decrease in planning and error processing task-related activation after treatment that was associated with symptom improvement, while individuals in the vertex rTMS group with greater symptom improvement showed an increase in inhibition-related activation. Conclusions: PreSMA and DLPFC rTMS combined with ERP led to significant symptom improvement related to activation decreases in targeted task networks, although we observed no differences in symptom reduction between groups. This trial was registered at clinicaltrials.gov ( NCT03667807 ).

Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study.

BACKGROUND: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated. OBJECTIVE: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group. METHODS: Cerebellar parcellation was performed using a deep learning-based approach from 2487 people with PD and 1212 age and sex-matched controls across 22 sites. Linear mixed effects models compared total and regional cerebellar volume in people with PD at each Hoehn and Yahr (HY) disease stage, to an age- and sex- matched control group. Associations with motor symptom severity and Montreal Cognitive Assessment scores were investigated. RESULTS: Overall, people with PD had a regionally smaller posterior lobe (dmax = -0.15). HY stage-specific analyses revealed a larger anterior lobule V bilaterally (dmax = 0.28) in people with PD in HY stage 1 compared to controls. In contrast, smaller bilateral lobule VII volume in the posterior lobe was observed in HY stages 3, 4, and 5 (dmax = -0.76), which was incrementally lower with higher disease stage. Within PD, cognitively impaired individuals had lower total cerebellar volume compared to cognitively normal individuals (d = -0.17). CONCLUSIONS: We provide evidence of a dissociation between anterior "motor" lobe and posterior "non-motor" lobe cerebellar regions in PD. Whereas less severe stages of the disease are associated with larger motor lobe regions, more severe stages of the disease are marked by smaller non-motor regions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.