Hearing Impairment: Reduced Pupil Dilation Response and Frontal Activation During Degraded Speech Perception.

PURPOSE: A relevant aspect of listening is the effort required during speech processing, which can be assessed by pupillometry. Here, we assessed the pupil dilation response of normal-hearing (NH) and hard of hearing (HH) individuals during listening to clear sentences and masked or degraded sentences. We combined this assessment with functional magnetic resonance imaging (fMRI) to investigate the neural correlates of the pupil dilation response. METHOD: Seventeen NH participants (Mage = 46 years) were compared to 17 HH participants (Mage = 45 years) who were individually matched in age and educational level. Participants repeated sentences that were presented clearly, that were distorted, or that were masked. The sentence intelligibility level of masked and distorted sentences was 50% correct. Silent baseline trials were presented as well. Performance measures, pupil dilation responses, and fMRI data were acquired. RESULTS: HH individuals had overall poorer speech reception than the NH participants, but not for noise-vocoded speech. In addition, an interaction effect was observed with smaller pupil dilation responses in HH than in NH listeners for the degraded speech conditions. Hearing impairment was associated with higher activation across conditions in the left superior temporal gyrus, as compared to the silent baseline. However, the region of interest analysis indicated lower activation during degraded speech relative to clear speech in bilateral frontal regions and the insular cortex, for HH compared to NH listeners. Hearing impairment was also associated with a weaker relation between the pupil response and activation in the right inferior frontal gyrus. Overall, degraded speech evoked higher frontal activation than clear speech. CONCLUSION: Brain areas associated with attentional and cognitive-control processes may be increasingly recruited when speech is degraded and are related to the pupil dilation response, but this relationship is weaker in HH listeners. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.27162135.

Glutamate dynamics and BOLD response during OCD symptom provocation in the lateral occipital cortex: A 7 Tesla fMRI-fMRS study.

Obsessive-compulsive disorder (OCD) is linked with dysfunction in frontal-striatal, fronto-limbic, and visual brain regions. Research using proton magnetic resonance spectroscopy (1H-MRS) suggests that altered neurometabolite levels, like glutamate, may contribute to this dysfunction. However, static neurometabolite levels in OCD patients have shown inconsistent results, likely due to previous studies' limited focus on neurometabolite dynamics. We employ functional MRS (fMRS) and functional magnetic resonance imaging (fMRI) to explore these dynamics and brain activation during OCD symptom provocation. We utilized a combined 7-tesla fMRI-fMRS setup to examine task-related BOLD response and glutamate changes in the lateral occipital cortex (LOC) of 30 OCD participants and 34 matched controls during an OCD-specific symptom provocation task. The study examined main effects and between-group differences in brain activation and glutamate levels during the task. A whole sample task-effects analysis on data meeting predefined quality criteria showed significant glutamate increases (n = 41 (22 OCD, 19 controls), mean change: 3.2 %, z = 3.75, p < .001) and task activation (n = 54 (26 OCD, 28 controls), p < .001) in the LOC during OCD blocks compared to neutral blocks. However, no differences in task-induced glutamate dynamics or activation between groups were found, nor a correlation between glutamate levels and task activation. We were able to measure task-induced increases in glutamate and BOLD levels, emphasizing its feasibility for OCD research. The absence of group differences highlights the need for further exploration to discern to what extent neurometabolite dynamics differ between OCD patients and controls. Once established, future studies can use pre-post intervention fMRS-fMRI to probe the effects of therapies modulating glutamate pathways in OCD.

TMS-induced plasticity improving cognitive control in OCD II: Task-based neural predictors of treatment response.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has the potential to increase the clinical effect of exposure with response prevention (ERP) psychotherapy for obsessive-compulsive disorder (OCD). We investigated the use of task-based functional MRI (tb-fMRI) for predicting clinical outcomes to different rTMS protocols combined with ERP in OCD. METHOD: 61 adults with OCD underwent rTMS and ERP and were randomized to different high frequency rTMS conditions: left dorsolateral prefrontal cortex (DLPFC; n=19), left pre-supplementary motor area (preSMA; n=23), and control stimulation at the vertex at low intensity (n=19). The Tower of London task and Stop-Signal Task were used to assess pretreatment activation during planning and inhibitory control, respectively. We adopted a Bayesian region-based approach to test whether clinical improvement can be predicted by tb-fMRI-derived measures of task-related brain activation or functional connectivity between task-relevant regions and the bilateral amygdala. RESULTS: For the vertex group, but not the DLPFC/preSMA rTMS conditions, higher activation in several task-relevant regions during planning and response inhibition, and lower error-related activation, corresponded with better short-term clinical improvement. Lower precuneus activation with increased planning taskload correlated with symptom reduction in the DLPFC group. In the preSMA group, higher error-related activation and lower inhibition-related insular-amygdalar connectivity was associated with symptom reduction. CONCLUSIONS: Pretreatment tb-fMRI-derived measures of activation and connectivity during planning and inhibition-related processes are associated with clinical response for specific rTMS conditions in OCD. Future placebo-controlled trials with larger sample sizes should combine clinical information and neural correlates to improve prediction of clinical outcome.

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.

Transcranial Magnetic Stimulation-Induced Plasticity Improving Cognitive Control in Obsessive-Compulsive Disorder, Part I: Clinical and Neuroimaging Outcomes From a Randomized 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 3 different rTMS protocols, all combined with exposure and response prevention. METHODS: In this 3-arm proof-of-concept randomized trial, 61 treatment-refractory adult patients with OCD received 16 sessions of rTMS immediately before exposure and response prevention over 8 weeks, with task-based functional magnetic resonance imaging scans and clinical assessments before and after treatment. Patients received high-frequency rTMS to the left dorsolateral prefrontal cortex (n = 19 [13 women/6 men]), high-frequency rTMS to the left pre-supplementary motor area (preSMA) (n = 23 [13 women/10 men]), or control rTMS to the vertex (n = 19 [13 women/6 men]). Changes in task-based functional magnetic resonance imaging activation before/after 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 (Δ = -10.836, p < .001, 95% CI -12.504 to -9.168), with no differences between groups. Response rate in the entire sample was 57.4%. The dorsolateral prefrontal cortex rTMS group showed decreased planning-related activation after treatment that was associated with greater symptom improvement. No group-level activation changes were observed for the preSMA and vertex rTMS groups. Participants in the preSMA group with greater symptom improvement showed decreased error-related activation, and symptom improvement in the vertex group was associated with increased inhibition-related activation. CONCLUSIONS: rTMS to preSMA and dorsolateral prefrontal cortex combined with exposure and response prevention led to activation decreases in targeted task networks in individuals showing greater symptom improvement, although we observed no differences in symptom reduction between groups.

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.

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 ).

Dopamine Transporter Availability in Early Parkinson's Disease is Dependent on Sunlight Exposure.

BACKGROUND: Preliminary studies suggested seasonality of dopaminergic functioning, but it is unknown whether dopamine transporter (DAT) expression in humans is also dependent on the seasons. We, therefore, investigated seasonal and sunlight-dependent effects on DAT availability in early Parkinson's disease (PD) patients and healthy controls. METHODS: DAT single-photon emission computed tomography scans (n = 730) were gathered from the Parkinson's Progression Marker Initiative (PPMI) database. We used global horizontal irradiance (GHI) as proxy for sun exposure/month and assessed associations between striatal DAT availability and season (autumn/winter versus spring/summer), GHI and latitude of the PPMI site. RESULTS: In PD patients, DAT availability in the left caudate nucleus was higher in spring/summer (B [standard error (SE)] = 0.05 [0.02], P = 0.03) and positively associated with higher sun exposure (B [SE] = 0.59 [0.22] × 10-3 , P = 0.007). Latitude (in degrees north) of the PPMI site was negatively associated with DAT availability in both PD and healthy controls. CONCLUSION: Striatal DAT availability may be influenced by daylight exposure. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Multimodal multilayer network centrality relates to executive functioning.

Executive functioning (EF) is a higher order cognitive process that is thought to depend on a network organization facilitating integration across subnetworks, in the context of which the central role of the fronto-parietal network (FPN) has been described across imaging and neurophysiological modalities. However, the potentially complementary unimodal information on the relevance of the FPN for EF has not yet been integrated. We employ a multilayer framework to allow for integration of different modalities into one 'network of networks.' We used diffusion MRI, resting-state functional MRI, MEG, and neuropsychological data obtained from 33 healthy adults to construct modality-specific single-layer networks as well as a single multilayer network per participant. We computed single-layer and multilayer eigenvector centrality of the FPN as a measure of integration in this network and examined their associations with EF. We found that higher multilayer FPN centrality, but not single-layer FPN centrality, was related to better EF. We did not find a statistically significant change in explained variance in EF when using the multilayer approach as compared to the single-layer measures. Overall, our results show the importance of FPN integration for EF and underline the promise of the multilayer framework toward better understanding cognitive functioning.

(HIIT-The Track) High-Intensity Interval Training for People with Parkinson's Disease: Individual Response Patterns of (Non-)Motor Symptoms and Blood-Based Biomarkers-A Crossover Single-Case Experimental Design.

INTRODUCTION: Physical exercise is receiving increasing interest as an augmentative non-pharmacological intervention in Parkinson's disease (PD). This pilot study primarily aimed to quantify individual response patterns of motor symptoms to alternating exercise modalities, along with non-motor functioning and blood biomarkers of neuroplasticity and neurodegeneration. MATERIALS & METHODS: People with PD performed high-intensity interval training (HIIT) and continuous aerobic exercise (CAE) using a crossover single-case experimental design. A repeated assessment of outcome measures was conducted. The trajectories of outcome measures were visualized in time series plots and interpreted relative to the minimal clinically important difference (MCID) and smallest detectable change (SDC) or as a change in the positive or negative direction using trend lines. RESULTS: Data of three participants were analyzed and engaging in physical exercise seemed beneficial for reducing motor symptoms. Participant 1 demonstrated improvement in motor function, independent of exercise modality; while for participant 2, such a clinically relevant (positive) change in motor function was only observed in response to CAE. Participant 3 showed improved motor function after HIIT, but no comparison could be made with CAE because of drop-out. Heterogeneous responses on secondary outcome measures were found, not only between exercise modalities but also among participants. CONCLUSION: Though this study underpins the positive impact of physical exercise in the management of PD, large variability in individual response patterns to the interventions among participants makes it difficult to identify clear exercise-induced adaptations in functioning and blood biomarkers. Further research is needed to overcome methodological challenges in measuring individual response patterns.

Poor Insight in Obsessive-Compulsive Disorder as a Multifaceted Phenomenon: Evidence From Brain Activation During Symptom Provocation.

BACKGROUND: Poor insight in obsessive-compulsive disorder (OCD) is associated with higher symptom severity, more comorbidities, and worse response to treatment. This study aimed to elucidate underlying mechanisms of poor insight in OCD by exploring its neurobiological correlates. METHODS: Using a symptom provocation task during functional magnetic resonance imaging, we compared brain activation of patients with poor insight (n = 19; 14 female, 5 male), good/fair insight (n = 63; 31 female, 32 male), and healthy control participants (n = 42; 22 female, 20 male) using a Bayesian region-of-interest and a general linear model whole-brain approach. Insight was assessed using the Overvalued Ideas Scale. RESULTS: Compared with patients with good/fair insight and healthy control participants, patients with OCD and poor insight showed widespread lower task-related activation in frontal areas (subgenual anterior cingulate cortex, ventromedial prefrontal cortex, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, supplementary motor area, precentral gyrus), parietal areas (posterior parietal cortex, precuneus), and the middle temporal gyrus and insula. Results were not driven by interindividual differences in OCD symptom severity, medication usage, age of disorder onset, or state distress levels. CONCLUSIONS: During symptom provocation, patients with OCD and poor insight show altered activation in brain circuits that are involved in emotional processing, sensory processing, and cognitive control. Future research should focus on longitudinal correlates of insight and/or use tasks that probe emotional and sensory processing and cognitive control.

Global multi-center and multi-modal magnetic resonance imaging study of obsessive-compulsive disorder: Harmonization and monitoring of protocols in healthy volunteers and phantoms.

OBJECTIVES: We describe the harmonized MRI acquisition and quality assessment of an ongoing global OCD study, with the aim to translate representative, well-powered neuroimaging findings in neuropsychiatric research to worldwide populations. METHODS: We report on T1-weighted structural MRI, resting-state functional MRI, and multi-shell diffusion-weighted imaging of 140 healthy participants (28 per site), two traveling controls, and regular phantom scans. RESULTS: Human image quality measures (IQMs) and outcome measures showed smaller within-site variation than between-site variation. Outcome measures were less variable than IQMs, especially for the traveling controls. Phantom IQMs were stable regarding geometry, SNR, and mean diffusivity, while fMRI fluctuation was more variable between sites. CONCLUSIONS: Variation in IQMs persists, even for an a priori harmonized data acquisition protocol, but after pre-processing they have less of an impact on the outcome measures. Continuous monitoring IQMs per site is valuable to detect potential artifacts and outliers. The inclusion of both cases and healthy participants at each site remains mandatory.

Cross-national harmonization of neurocognitive assessment across five sites in a global study.

OBJECTIVE: Cross-national work on neurocognitive testing has been characterized by inconsistent findings, suggesting the need for improved harmonization. Here, we describe a prospective harmonization approach in an ongoing global collaborative study. METHOD: Visuospatial N-Back, Tower of London (ToL), Stop Signal task (SST), Risk Aversion (RA), and Intertemporal Choice (ITC) tasks were administered to 221 individuals from Brazil, India, the Netherlands, South Africa, and the USA. Prospective harmonization methods were employed to ensure procedural similarity of task implementation and processing of derived task measures across sites. Generalized linear models tested for between-site differences controlling for sex, age, education, and socioeconomic status (SES). Associations with these covariates were also examined and tested for differences by site with site-by-covariate interactions. RESULTS: The Netherlands site performed more accurately on N-Back and ToL than the other sites, except for the USA site on the N-Back. The Netherlands and the USA sites performed faster than the other three sites during the go events in the SST. Finally, the Netherlands site also exhibited a higher tolerance for delay discounting than other sites on the ITC, and the India site showed more risk aversion than other sites on the RA task. However, effect size differences across sites on the five tasks were generally small (i.e., partial eta-squared < 0.05) after dropping the Netherlands (on ToL, N-Back, ITC, and SST tasks) and India (on the RA task). Across tasks, regardless of site, the N-Back (sex, age, education, and SES), ToL (sex, age, and SES), SST (age), and ITC (SES) showed associations with covariates. CONCLUSIONS: Four out of the five sites showed only small between-site differences for each task. Nevertheless, despite our extensive prospective harmonization steps, task score performance deviated from the other sites in the Netherlands site (on four tasks) and the India site (on one task). Because the procedural methods were standardized across sites, and our analyses were adjusted for covariates, the differences found in cognitive performance may indicate selection sampling bias due to unmeasured confounders. Future studies should follow similar cross-site prospective harmonization procedures when assessing neurocognition and consider measuring other possible confounding variables for additional statistical control. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Abnormal white-matter rich-club organization in obsessive-compulsive disorder.

Rich-club organization is key to efficient global neuronal signaling and integration of information. Alterations interfere with higher-order cognitive processes, and are common to several psychiatric and neurological conditions. A few studies examining the structural connectome in obsessive-compulsive disorder (OCD) suggest lower efficiency of information transfer across the brain. However, it remains unclear whether this is due to alterations in rich-club organization. In the current study, the structural connectome of 28 unmedicated OCD patients, 8 of their unaffected siblings and 28 healthy controls was reconstructed by means of diffusion-weighted imaging and probabilistic tractography. Topological and weighted measures of rich-club organization and connectivity were computed, alongside global and nodal measures of network integration and segregation. The relationship between clinical scores and network properties was explored. Compared to healthy controls, OCD patients displayed significantly lower topological and weighted rich-club organization, allocating a smaller fraction of all connection weights to the rich-club core. Global clustering coefficient, local efficiency, and clustering of nonrich club nodes were significantly higher in OCD patients. Significant three-group differences emerged, with siblings displaying highest and lowest values in different measures. No significant correlation with any clinical score was found. Our results suggest weaker structural connectivity between rich-club nodes in OCD patients, possibly resulting in lower network integration in favor of higher network segregation. We highlight the need of looking at network-based alterations in brain organization and function when investigating the neurobiological basis of this disorder, and stimulate further research into potential familial protective factors against the development of OCD.

Effect of eight-week online cognitive training in Parkinson's disease: A double-blind, randomized, controlled trial.

INTRODUCTION: Cognitive training (CT) has been proposed as a treatment option for cognitive impairment in Parkinson's disease (PD). We aimed to assess the efficacy of adaptive, computerized CT on cognitive function in PD. METHODS: In this double-blind, randomized controlled trial we enrolled PD patients that experienced substantial subjective cognitive complaints. Over a period of eight weeks, participants underwent 24 sessions of computerized multi-domain CT or an active control intervention for 45 min each (randomized 1:1). The primary outcome was the accuracy on the Tower of London task; secondary outcomes included effects on other neuropsychological outcomes and subjective cognitive complaints. Outcomes were assessed before and after training and at six-months follow-up, and analyzed with multivariate mixed-model analyses. RESULTS: The intention-to-treat population consisted of 136 participants (n = 68 vs. n = 68, age M: 62.9y, female: 39.7%). Multivariate mixed-model analyses showed no group difference on the Tower of London accuracy corrected for baseline performance (n = 130): B: -0.06, 95% CI: -0.27 to 0.15, p = 0.562. Participants in the CT group were on average 0.30 SD (i.e., 1.5 s) faster on difficulty load 4 of this task (secondary outcome): 95% CI: -0.55 to -0.06, p = 0.015. CT did not reduce subjective cognitive complaints. At follow-up, no group differences were found. CONCLUSIONS: This study shows no beneficial effect of eight-week computerized CT on the primary outcome (i.e., planning accuracy) and only minor improvements on secondary outcomes (i.e., processing speed) with limited clinical impact. Personalized or ecologically valid multi-modal intervention methods could be considered to achieve clinically meaningful and lasting effects.

A hands-on tutorial on network and topological neuroscience.

The brain is an extraordinarily complex system that facilitates the optimal integration of information from different regions to execute its functions. With the recent advances in technology, researchers can now collect enormous amounts of data from the brain using neuroimaging at different scales and from numerous modalities. With that comes the need for sophisticated tools for analysis. The field of network neuroscience has been trying to tackle these challenges, and graph theory has been one of its essential branches through the investigation of brain networks. Recently, topological data analysis has gained more attention as an alternative framework by providing a set of metrics that go beyond pairwise connections and offer improved robustness against noise. In this hands-on tutorial, our goal is to provide the computational tools to explore neuroimaging data using these frameworks and to facilitate their accessibility, data visualisation, and comprehension for newcomers to the field. We will start by giving a concise (and by no means complete) overview of the field to introduce the two frameworks and then explain how to compute both well-established and newer metrics on resting-state functional magnetic resonance imaging. We use an open-source language (Python) and provide an accompanying publicly available Jupyter Notebook that uses the 1000 Functional Connectomes Project dataset. Moreover, we would like to highlight one part of our notebook dedicated to the realistic visualisation of high order interactions in brain networks. This pipeline provides three-dimensional (3-D) plots of pairwise and higher-order interactions projected in a brain atlas, a new feature tailor-made for network neuroscience.

Eight-week multi-domain cognitive training does not impact large-scale resting-state brain networks in Parkinson's disease.

There is meta-analytic evidence for the efficacy of cognitive training (CT) in Parkinson's disease (PD). We performed a randomized controlled trial where we found small positive effects of CT on executive function and processing speed in individuals with PD (ntotal = 140). In this study, we assessed the effects of CT on brain network connectivity and topology in a subsample of the full study population (nmri = 86). Participants were randomized into an online multi-domain CT and an active control condition and performed 24 sessions of either intervention in eight weeks. Resting-state functional MRI scans were acquired in addition to extensive clinical and neuropsychological assessments pre- and post-intervention. In line with our preregistered analysis plan (osf.io/3st82), we computed connectivity between 'cognitive' resting-state networks and computed topological outcomes at the whole-brain and sub-network level. We assessed group differences after the intervention with mixed-model analyses adjusting for baseline performance and analyzed the association between network and cognitive performance changes with repeated measures correlation analyses. The final analysis sample consisted of 71 participants (n CT = 37). After intervention there were no group differences on between-network connectivity and network topological outcomes. No associations between neural network and neuropsychological performance change were found. CT increased segregated network topology in a small sub-sample of cognitively intact participants. Post-hoc nodal analyses showed post-intervention enhanced connectivity of both the dorsal anterior cingulate cortex and dorsolateral prefrontal cortex in the CT group. The results suggest no large-scale brain network effects of eight-week computerized CT, but rather localized connectivity changes of key regions in cognitive function, that potentially reflect the specific effects of the intervention.

Longitudinal changes in neurometabolite concentrations in the dorsal anterior cingulate cortex after concentrated exposure therapy for obsessive-compulsive disorder.

BACKGROUND: The dorsal anterior cingulate cortex (dACC) plays an important role in the pathophysiology of obsessive-compulsive disorder (OCD) due to its role in error processing, cognitive control and emotion regulation. OCD patients have shown altered concentrations in neurometabolites in the dACC, particularly Glx (glutamate+glutamine) and tNAA (N-acetylaspartate+N-acetyl-aspartyl-glutamate). We investigated the immediate and prolonged effects of exposure and response prevention (ERP) on these neurometabolites. METHODS: Glx and tNAA concentrations were measured using magnetic resonance spectroscopy (1H-MRS) in 24 OCD patients and 23 healthy controls at baseline. Patients received concentrated ERP over four days. A subset was re-scanned after one week and three months. RESULTS: No Glx and tNAA abnormalities were observed in OCD patients compared to healthy controls before treatment or over time. Patients with childhood or adult onset differed in the change over time in tNAA (F(2,40) = 7.24, É³2p= 0.27, p = 0.004): concentrations increased between one week after treatment and follow-up in the childhood onset group (t(39) = -2.43, d = -0.86, p = 0.020), whereas tNAA concentrations decreased between baseline and follow-up in patients with an adult onset (t(42) = 2.78, d = 1.07, p = 0.008). In OCD patients with versus without comorbid mood disorders, lower Glx concentrations were detected at baseline (t(38) = -2.28, d = -1.00, p = 0.028). Glx increased after one week of treatment within OCD patients with comorbid mood disorders (t(30) = -3.09, d = -1.21, p = 0.004). LIMITATIONS: Our OCD sample size allowed the detection of moderate to large effect sizes only. CONCLUSION: ERP induced changes in neurometabolites in OCD seem to be dependent on mood disorder comorbidity and disease stage rather than OCD itself.