Search

Background: Clinicians are often hesitant to use trauma-focused therapy for patients with personality disorders (PDs) because of concerns that the pathology may worsen.Objective: Exploring trajectories of change and individual exacerbations in psychological distress and suicidal thoughts in patients with a PD without comorbid posttraumatic stress disorder (PTSD) during EMDR therapy or waiting time.Method: In a randomized controlled trial, the effectiveness of five sessions of EMDR therapy was compared with a waitlist in 97 outpatients. Acute suicidal patients were not included in this study. Psychological distress and suicidality scores were measured on a weekly basis during the EMDR and waiting list (WL) periods and at 3-month follow-up. Data were analysed in a descriptive manner for individual patients, and hierarchical cluster analysis was used to identify patterns of change among clusters of patients. Mann–Whitney U and chi-squared tests were used to explore differences in specific patient characteristics between the found clusters of patients.Results: Patients generally improved, and no clusters of patients deteriorated during the EMDR therapy. Session-to-session exacerbations occurred in both the EMDR (psychological distress: 10.0%; suicidal thoughts: 28.0%) and WL group (psychological distress: 28.0%; suicidal thoughts: 43.5%). Two percent of patients in the EMDR group and 8.7% of patients in the WL condition showed an increase in psychological distress, whereas 2.0% of patients in the EMDR group and 10.9% of patients in the WL condition showed an increase in suicidal thoughts posttreatment compared to baseline.Conclusions: These results show that although individual exacerbations in psychological distress and suicidal thoughts occur, these were less likely to occur in response to EMDR therapy compared with no therapy. Continuation of therapy following exacerbation led to a decrease in psychological distress and suicidal thoughts in most patients.

Research has shown that the impact of traumatic events and circumstances on individuals is cumulative and potentially has a wide range of harmful consequences, including negative consequences on mental health. One such consequence is the development of a personality disorder, a persistent mental condition characterized by a pronounced pattern of difficulties in impulse control, emotional regulation, cognitive functions, self-esteem, and interpersonal relationships. A wide array of studies indicates that the personal history of individuals with a personality disorder is often marked by exposure to traumatic events or other types of adverse childhood experiences (ACEs). Because existing treatments for personality disorders are usually long and costly, it is essential to continue exploring alternative and complementary interventions. Nowadays, knowledge and clinical experience in regard to personality disorders have been gained in addressing ACEs by processing memories of these events through eye movement desensitization and reprocessing (EMDR) therapy. In this paper, we present a theoretical framework for this treatment approach, based on Shapiro’s Adaptive Information Processing (AIP) model, describe its current empirical basis, and provide guidance on how to formulate a useful case conceptualization that can serve as a basis for the treatment of personality disorders with EMDR therapy. This approach is illustrated with a case example.

BackgroundExposure to adverse childhood events plays an important role in the development of borderline personality disorder (BPD). Emerging evidence suggests that trauma-focused therapy using eye movement desensitization and reprocessing (EMDR) can be beneficial for patients with BPD symptoms. To date, the effects of brief, intensive EMDR treatment for this target group have not been investigated in this population.ObjectiveThis study aimed to evaluate the effects of a brief and intensive trauma-focused therapy course using EMDR therapy in two patients diagnosed with BPD who did not fulfill the diagnostic criteria for post-traumatic stress disorder (PTSD). It was hypothesized that this approach would be associated with a decline in the core symptoms of BPD, and that this would have an enduring long-term effect on patients’ diagnostic status.MethodTen sessions of EMDR therapy were carried out across four consecutive treatment days, with the aim of processing patients’ core adverse childhood experiences. Both A-criterion-worthy memories (without intrusive reliving) and non-A-criterion-worthy memories that were considered responsible for the patients’ most prominent symptoms were targeted. The effects of EMDR therapy on trauma symptom severity and BPD diagnostic status (as established by the Structured Clinical Interview DSM-5) were determined. Additionally, the effects on psychological distress, quality of life, and difficulties in emotion regulation were determined at intake, post-treatment, and at 3-, 6-, and 12-months follow-up.ResultsBoth patients showed a strong decline in psychological distress and difficulties in emotion regulation, and reported an improvement in their quality of life. At post-treatment, and at 3-, 6-, and 12-months follow-up they no longer met the DSM-5 criteria for BPD.ConclusionThe findings of this small case study are in line with mounting evidence that a brief track of intensive trauma-focused therapy can result in long-term remission in patients with BPD. EMDR therapy seems to be a promising treatment approach for patients with BPD; however, the results need to be replicated in clinical trials.

Obtaining adequate understanding of scientific concepts is considered challenging due to learners' misconceptions about natural phenomena. Misconceptions may coexist with scientific knowledge in the brain. Therefore, misconceptions must be cognitively inhibited in order to select the scientific knowledge. There is, however, lack of substantial neuroscientific evidence supporting this hypothesis. In this study, we sought for this evidence by investigating medical students who solved a cardiovascular conceptual problem in a magnetic resonance imaging scanner. Brain activation was compared between understanders who had the scientific knowledge, and misunderstanders who held a misconception. No significant activation was found in brain areas related to cognitive inhibition in understanders compared with misunderstanders. Therefore, we could not confirm the idea that cognitive inhibition is involved in overcoming a misconception. Instead, we found that the putamen was significantly activated in misunderstanders compared with understanders, suggesting a role for episodic memory in learners holding a misconception.

Abstract Background Existing recommended treatment options for personality disorders (PDs) are extensive and costly. There is emerging evidence indicating that trauma-focused treatment using eye movement desensitization and reprocessing (EMDR) therapy aimed at resolving memories of individuals’ adverse events can be beneficial for this target group within a relatively short time frame. The primary purpose of the present study is to determine the effectiveness of EMDR therapy versus waiting list in reducing PD symptom severity. Furthermore, the effects of EMDR therapy on trauma symptom severity, loss of diagnosis, personal functioning, quality of life, and mental health outcomes will be determined. In addition, the cost-effectiveness of EMDR therapy in the treatment of PDs is investigated. Moreover, predictors of treatment success, symptom deterioration and treatment discontinuation will be assessed. Lastly, experiences with EMDR therapy will be explored. Method In total, 159 patients with a PD will be included in a large multicentre single-blind randomized controlled trial. The Structured Clinical Interview for DSM-5 Personality Disorders will be used to determine the presence of a PD. Participants will be allocated to either a treatment condition with EMDR therapy (ten biweekly 90-min sessions) or a waiting list. Three months after potential treatment with EMDR therapy, patients can receive treatment as usual for their PD. All participants are subject to single-blinded baseline, post-intervention and 3-, 6- and 12-month follow-up assessments. The primary outcome measures are the Assessment of DSM-IV Personality Disorders and the Clinician-Administered PTSD Scale for DSM-5. For cost-effectiveness, the Treatment Inventory of Costs in Patients with psychiatric disorders, EuroQol-5D-3L, and the Mental Health Quality of Life Questionnaire will be administered. The PTSD Checklist for DSM-5, Brief State Paranoia Checklist and Difficulties in Emotion Regulation Scale will be used to further index trauma symptom severity. Type of trauma is identified at baseline with the Childhood Trauma Questionnaire-SF and Life Events Checklist for the DSM-5. Personal functioning and health outcome are assessed with the Level of Personality Functioning Scale-BF 2.0, Outcome Questionnaire-45 and Mental Health Quality of Life Questionnaire. Experiences with EMDR therapy of patients in the EMDR therapy condition are explored with a semi-structured interview at post-intervention. Discussion It is expected that the results of this study will contribute to knowledge about the effectiveness, and cost-effectiveness of trauma-focused treatment using EMDR therapy in individuals diagnosed with a PD. Follow-up data provide documentation of long-term effects of EMDR therapy on various outcome variables, most importantly the reduction of PD symptom severity and loss of diagnoses. Trial registration Netherlands Trial Register NL9078 . Registered on 31 November 2020

Cerebral amyloid angiopathy (CAA) is frequently found post mortem in Alzheimer's dementia, but often undetected during life especially since in vivo hallmarks of CAA and its vascular damage become overt relatively late in the disease process. Decreased neurovascular coupling to visual stimulation has been put forward as an early MRI marker for CAA disease severity. The current study investigates the role of neurovascular coupling in AD related dementia and its early stages. We included 25 subjective cognitive impairment, 33 mild cognitive impairment and 17 dementia patients and 44 controls. All participants underwent magnetic resonance imaging of the brain and neuropsychological assessment. Univariate general linear modeling analyses were used to assess neurovascular coupling between patient groups and controls. Moreover, linear regression analyses was used to assess the associations between neurovascular coupling and cognition. Our data show that BOLD amplitude is lower in dementia (mean 0.8 ± 0.2, p = 0.001) and MCI patients (mean 0.9 ± 0.3, p = 0.004) compared with controls (mean 1.1 ± 0.2). A low BOLD amplitude was associated with low scores in multiple cognitive domains. We conclude that cerebrovascular dysfunction, most likely due CAA, is an important comorbidity in early stages of dementia and has an independent effect on cognition. [ABSTRACT FROM AUTHOR]

Objective: Complex post‐traumatic stress disorder (CPTSD) is a classification within the International Classification of Diseases, 11th Revision (ICD‐11) that, besides the DSM‐5 symptom clusters of post‐post‐traumatic stress disorder (PTSD), includes the presence of negative self‐concept, difficulties in regulating emotions and relationship skills. The purpose of the present study was to provide guidance on how to deliver Eye Movement Desensitization and Reprocessing (EMDR) therapy in the context of CPTSD, based on current clinical knowledge and the latest scientific research findings. Method: This paper describes the treatment of a 52‐year‐old woman with CPTSD and borderline personality disorder for which immediate trauma‐focused EMDR therapy was used. Results: First, a description of what EMDR therapy entails and some important treatment strategies that the therapist may employ to assist in trauma‐focused treatment of clients with CPTSD using EMDR therapy are outlined. Conclusion: The treatment results are in line with mounting evidence supporting the notion that EMDR therapy is a safe and potentially effective treatment alternative for individuals with CPTSD or personality problems. [ABSTRACT FROM AUTHOR]

Background: Little is known about the effects of targeting memories of adverse (childhood) events in people with a personality disorder (PD). Objective: Determining the effectiveness of brief EMDR therapy in individuals with PD. Method: In a randomized-controlled trial, 97 outpatients with a PD as main diagnosis were allocated to either five (90 minutes) sessions of EMDR therapy (n = 51) or a waiting list (WL) control condition (n = 46) followed by 3 months of treatment as usual for their PD. Individuals with posttraumatic stress disorder (PTSD) were excluded. Measurements were performed on psychological symptoms, psychological distress, and personality dysfunctioning. Outcomes were compared at baseline, post-treatment, and at 3-month follow up. Data were analysed as intent-to-treat with linear mixed models. Results: EMDR therapy yielded significant improvements with medium to large effect sizes for the primary outcomes after treatment, i.e. psychological symptoms (EMDR: d =.42; control group: d =.07), psychological distress (EMDR: d =.69; control group: d =.29), and personality functioning (EMDR: d =.41; control group: d = −.10) within groups. At 3-month follow-up, after 3 months of TAU, improvements were maintained. Significant differences were found between both groups regarding all outcome measures in favour of the EMDR group at post-treatment (ds between −.62 and −.65), and at follow-up, after 3 months of TAU (ds between −.45 and −.53). Conclusions: The results suggest that EMDR therapy can be beneficial in the treatment of patients with PDs. More rigorous outcome research examining long-term effects and using a longer treatment track is warranted.

Neuroimaging MRI data in scientific research is increasingly pooled, but the reliability of such studies may be hampered by the use of different hardware elements. This might introduce bias, for example when cross-sectional studies pool data acquired with different head coils, or when longitudinal clinical studies change head coils halfway. In the present study, we aimed to estimate this possible bias introduced by using different head coils to create awareness and to avoid misinterpretation of results. We acquired, with both an 8 channel and 32 channel head coil, T1-weighted, diffusion tensor imaging and resting state fMRI images at 3T MRI (Philips Achieva) with stable acquisition parameters in a large group of cognitively healthy participants (n = 77). Standard analysis methods, i.e., voxel-based morphometry, tract-based spatial statistics and resting state functional network analyses, were used in a within-subject design to compare 8 and 32 channel head coil data. Signal-to-noise ratios (SNR) for both head coils showed similar ranges, although the 32 channel SNR profile was more homogeneous. Our data demonstrates specific patterns of gray and white matter volume differences between head coils (relative volume change of 6 to 9%), related to altered image contrast and therefore, altered tissue segmentation. White matter connectivity (fractional anisotropy and diffusivity measures) showed hemispherical dependent differences between head coils (relative connectivity change of 4 to 6%), and functional connectivity in resting state networks was higher using the 32 channel head coil in posterior cortical areas (relative change up to 27.5%). This study shows that, even when acquisition protocols are harmonized, the results of standardized analysis models can be severely affected by the use of different head coils. Researchers should be aware of this when combining multiple neuroimaging MRI datasets, to prevent coil-related bias and avoid misinterpretation of their findings.

Background: Progressive subcortical changes are known to occur in Huntington's disease (HD), a hereditary neurodegenerative disorder. Less is known about the occurrence and cohesion of whole brain grey matter changes in HD. Objectives: We aimed to detect network integrity changes in grey matter structural covariance networks and examined relationships with clinical assessments. Methods: Structural magnetic resonance imaging data of premanifest HD (n = 30), HD patients (n = 30) and controls (n = 30) was used to identify ten structural covariance networks based on a novel technique using the co-variation of grey matter with independent component analysis in FSL. Group differences were studied controlling for age and gender. To explore whether our approach is effective in examining grey matter changes, regional voxel-based analysis was additionally performed. Results: Premanifest HD and HD patients showed decreased network integrity in two networks compared to controls. One network included the caudate nucleus, precuneous and anterior cingulate cortex (in HD p

Objective: Frontotemporal dementia (FTD) is characterized by behavioral disturbances and language problems. Familial forms can be caused by genetic defects in microtubule-associated protein tau (MAPT), progranulin (GRN), and C9orf72. In light of upcoming clinical trials with potential disease-modifying agents, the development of sensitive biomarkers to evaluate such agents in the earliest stage of FTD is crucial. In the current longitudinal study we used arterial spin labeling MRI (ASL) in presymptomatic carriers of MAPT and GRN mutations to investigate early changes in cerebral blood flow (CBF). Methods: Healthy first-degree relatives of patients with a MAPT or GRN mutation underwent ASL at baseline and follow-up after two years. We investigated cross-sectional and longitudinal differences in CBF between mutation carriers (n = 34) and controls without a mutation (n = 31). Results: GRN mutation carriers showed significant frontoparietal hypoperfusion compared with controls at follow-up, whereas we found no cross-sectional group differences in the total study group or the MAPT subgroup. Longitudinal analyses revealed a significantly stronger decrease in CBF in frontal, temporal, parietal, and subcortical areas in the total group of mutation carriers and the GRN subgroup, with the strongest decrease in two mutation carriers who converted to clinical FTD during follow-up. Interpretation: We demonstrated longitudinal alterations in CBF in presymptomatic FTD independent of grey matter atrophy, with the strongest decrease in individuals that developed symptoms during follow-up. Therefore, ASL could have the potential to serve as a sensitive biomarker of disease progression in the presymptomatic stage of FTD in future clinical trials.

Magnetic resonance imaging (MRI) is sensitive to structural and functional changes in the brain caused by Alzheimer's disease (AD), and can therefore be used to help in diagnosing the disease. Improving classification of AD patients based on MRI scans might help to identify AD earlier in the disease's progress, which may be key in developing treatments for AD. In this study we used an elastic net classifier based on several measures derived from the MRI scans of mild to moderate AD patients (N=77) from the prospective registry on dementia study and controls (N=173) from the Austrian Stroke Prevention Family Study. We based our classification on measures from anatomical MRI, diffusion weighted MRI and resting state functional MRI. Our unimodal classification performance ranged from an area under the curve (AUC) of 0.760 (full correlations between functional networks) to 0.909 (grey matter density). When combining measures from multiple modalities in a stepwise manner, the classification performance improved to an AUC of 0.952. This optimal combination consisted of grey matter density, white matter density, fractional anisotropy, mean diffusivity, and sparse partial correlations between functional networks. Classification performance for mild AD as well as moderate AD also improved when using this multimodal combination. We conclude that different MRI modalities provide complementary information for classifying AD. Moreover, combining multiple modalities can substantially improve classification performance over unimodal classification.

Background: Functional imaging methods, such as resting-state functional magnetic resonance imaging, reflect changes in neural connectivity and may help to assess the widespread consequences of disease-specific network changes in Parkinson's disease. In this study we used a relatively new graph analysis approach in functional imaging: eigenvector centrality mapping. This model-free method, applied to all voxels in the brain, identifies prominent regions in the brain network hierarchy and detects localized differences between patient populations. In other neurological disorders, eigenvector centrality mapping has been linked to changes in functional connectivity in certain nodes of brain networks.Objectives: Examining changes in functional brain connectivity architecture on a whole brain and network level in patients with Parkinson's disease.Methods: Whole brain resting-state functional architecture was studied with a recently introduced graph analysis approach (eigenvector centrality mapping). Functional connectivity was further investigated in relation to eight known resting-state networks. Cross-sectional analyses included group comparison of functional connectivity measures of Parkinson's disease patients (n = 107) with control subjects (n = 58) and correlations with clinical data, including motor and cognitive impairment and a composite measure of predominantly non-dopaminergic symptoms.Results: Eigenvector centrality mapping revealed that frontoparietal regions were more prominent in the whole-brain network function in patients compared to control subjects, while frontal and occipital brain areas were less prominent in patients. Using standard resting-state networks, we found predominantly increased functional connectivity, namely within sensorimotor system and visual networks in patients. Regional group differences in functional connectivity of both techniques between patients and control subjects partly overlapped for highly connected posterior brain regions, in particular in the posterior cingulate cortex and precuneus. Clinico-functional imaging relations were not found.Conclusions: Changes on the level of functional brain connectivity architecture might provide a different perspective of pathological consequences of Parkinson's disease. The involvement of specific, highly connected (hub) brain regions may influence whole brain functional network architecture in Parkinson's disease.

We investigated the ability of cortical and subcortical gray matter (GM) atrophy in combination with white matter (WM) integrity to distinguish behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) and from controls using voxel-based morphometry, subcortical structure segmentation, and tract-based spatial statistics. To determine which combination of MR markers differentiated the three groups with the highest accuracy, we conducted discriminant function analyses. Adjusted for age, sex and center, both types of dementia had more GM atrophy, lower fractional anisotropy (FA) and higher mean (MD), axial (L1) and radial diffusivity (L23) values than controls. BvFTD patients had more GM atrophy in orbitofrontal and inferior frontal areas than AD patients. In addition, caudate nucleus and nucleus accumbens were smaller in bvFTD than in AD. FA values were lower; MD, L1 and L23 values were higher, especially in frontal areas of the brain for bvFTD compared to AD patients. The combination of cortical GM, hippocampal volume and WM integrity measurements, classified 97–100% of controls, 81–100% of AD and 67–75% of bvFTD patients correctly. Our results suggest that WM integrity measures add complementary information to measures of GM atrophy, thereby improving the classification between AD and bvFTD.

Background: Decreased cerebrovascular reactivity, measured as changes in blood‐oxygen‐level‐dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before clinical application, the effect of aging on BOLD parameters, and reproducibility and test–retest reliability of these parameters should be assessed. Purpose: Assess the effect of healthy aging on cerebrovascular reactivity (BOLD amplitude, time to peak, and time to baseline). And determine reproducibility and test–retest reliability of these parameters. Study Type: Prospective‐observational. Population: Eighty‐six healthy adults (mean age 56 years, 55% female), 10 presymptomatic D‐CAA mutation carriers (mean age 34 years, 70% female), and 10 symptomatic D‐CAA mutation carriers (mean age 54 years, 70% female). Field Strength/Sequence: 3‐T, three‐dimensional (3D) T1‐weighted MRI and gradient echo BOLD fMRI. Assessment: To assess test–retest reliability of BOLD parameters, i.e. BOLD amplitude, time to peak, and time to baseline, BOLD fMRI scans were repeated three times immediately after each other, in both controls and mutation carriers. To assess reproducibility, BOLD fMRI scans were repeated with a 3‐week interval for each subject. Statistical Tests: Linear regression analyses and two‐way mixed absolute agreement intra‐class correlation approach. Results: Healthy aging was associated with decreased BOLD amplitude (β = −0.711) and prolonged time to baseline (β = 0.236) in the visual cortex after visual stimulation Reproducibility of BOLD amplitude was excellent (ICC 0.940) in the subgroup of healthy adults. Test–retest reliability for BOLD amplitude was excellent in healthy adults (ICC 0.856–0.910) and presymptomatic D‐CAA mutation carriers (ICC 0.959–0.981). In symptomatic D‐CAA mutation carriers, test–retest reliability was poor for all parameters (ICCs < 0.5). Data Conclusion: Healthy aging is associated with decreased cerebrovascular reactivity, measured by changes in BOLD response to visual stimulation. The BOLD amplitude appears to be a robust measurement in healthy adults and presymptomatic D‐CAA mutation carriers, but not in symptomatic D‐CAA mutation carriers. [ABSTRACT FROM AUTHOR]

There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV) adjuvated with the saponin-based adjuvant Matrix-M (MM) can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

Proton magnetic resonance spectroscopy ((1)H MRS) is a valuable tool in Alzheimer's disease research, investigating the functional integrity of the brain. The present longitudinal study set out to characterize the neurochemical profile of the hippocampus, measured by single voxel (1)H MRS at 7 Tesla, in the brains of AβPPSswe-PS1dE9 and wild-type mice at 8 and 12 months of age. Furthermore, we wanted to determine whether alterations in hippocampal metabolite levels coincided with behavioral changes, cognitive decline and neuropathological features, to gain a better understanding of the underlying neurodegenerative processes. Moreover, correlation analyses were performed in the 12-month-old AβPP-PS1 animals with the hippocampal amyloid-β deposition, TBS-T soluble Aβ levels and high-molecular weight Aβ aggregate levels to gain a better understanding of the possible involvement of Aβ in neurochemical and behavioral changes, cognitive decline and neuropathological features in AβPP-PS1 transgenic mice. Our results show that at 8 months of age AβPPswe-PS1dE9 mice display behavioral and cognitive changes compared to age-matched wild-type mice, as determined in the open field and the (reverse) Morris water maze. However, there were no variations in hippocampal metabolite levels at this age. AβPP-PS1 mice at 12 months of age display more severe behavioral and cognitive impairment, which coincided with alterations in hippocampal metabolite levels that suggest reduced neuronal integrity. Furthermore, correlation analyses suggest a possible role of Aβ in inflammatory processes, synaptic dysfunction and impaired neurogenesis.

Plasma cells daily secrete their own mass in antibodies, which fold and assemble in the endoplasmic reticulum (ER). To reach these levels, cells require pERp1, a novel lymphocyte-specific small ER-resident protein, which attains expression levels as high as BiP when B cells differentiate into plasma cells. Although pERp1 has no homology with known ER proteins, it does contain a CXXC motif typical for oxidoreductases. In steady state, the CXXC cysteines are locked by two parallel disulfide bonds with a downstream C[(X).sub.6]C motif, and pERp1 displays only modest oxidoreductase activity, pERpl emerged as a dedicated folding factor for IgM, associating with both heavy and light chains and promoting assembly and secretion of mature IgM.