Age-Related Differences in Functional Nodes of the Brain Cortex – A High Model Order Group ICA Study

Functional MRI measured with blood oxygen dependent (BOLD) contrast in the absence of intermittent tasks reflects spontaneous activity of so-called resting state networks (RSN) of the brain. Group level independent component analysis (ICA) of BOLD data can separate the human brain cortex into 42 independent RSNs. In this study we evaluated age-related effects from primary motor and sensory, and, higher level control RSNs. One hundred sixty-eight healthy subjects were scanned and divided into three groups: 55 adolescents (ADO, 13.2 ± 2.4 years), 59 young adults (YA, 22.2 ± 0.6 years), and 54 older adults (OA, 42.7 ± 0.5 years), all with normal IQ. High model order group probabilistic ICA components (70) were calculated and dual-regression analysis was used to compare 21 RSN's spatial differences between groups. The power spectra were derived from individual ICA mixing matrix time series of the group analyses for frequency domain analysis. We show that primary sensory and motor networks tend to alter more in younger age groups, whereas associative and higher level cognitive networks consolidate and re-arrange until older adulthood. The change has a common trend: both spatial extent and the low frequency power of the RSN's reduce with increasing age. We interpret these result as a sign of normal pruning via focusing of activity to less distributed local hubs

Mapping Transient Hyperventilation Induced Alterations with Estimates of the Multi-Scale Dynamics of BOLD Signal

Temporal blood oxygen level dependent (BOLD) contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD) trends of the form 1/fα. Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF) after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant α, fractal dimension Df, and, Hurst exponent H) characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The α was able to differentiate also blood vessels from grey matter changes. Df was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow

m-RESIST, a Mobile Therapeutic Intervention for Treatment-Resistant Schizophrenia: Feasibility, Acceptability, and Usability Study

Mental disorder; Schizophrenia; Treatment-resistantTrastorno mental; Esquizofrenia; Resistentencia al tratamientoMalaltia mental; Esquizofrènia; Resistència al tractamentBackground: In the European Union, around 5 million people are affected by psychotic disorders, and approximately 30%-50% of people with schizophrenia have treatment-resistant schizophrenia (TRS). Mobile health (mHealth) interventions may be effective in preventing relapses, increasing treatment adherence, and managing some of the symptoms of schizophrenia. People with schizophrenia seem willing and able to use smartphones to monitor their symptoms and engage in therapeutic interventions. mHealth studies have been performed with other clinical populations but not in populations with TRS. Objective: The purpose of this study was to present the 3-month prospective results of the m-RESIST intervention. This study aims to assess the feasibility, acceptability, and usability of the m-RESIST intervention and the satisfaction among patients with TRS after using this intervention. Methods: A prospective multicenter feasibility study without a control group was undertaken with patients with TRS. This study was performed at 3 sites: Sant Pau Hospital (Barcelona, Spain), Semmelweis University (Budapest, Hungary), and Sheba Medical Center and Gertner Institute of Epidemiology and Health Policy Research (Ramat-Gan, Israel). The m-RESIST intervention consisted of a smartwatch, a mobile app, a web-based platform, and a tailored therapeutic program. The m-RESIST intervention was delivered to patients with TRS and assisted by mental health care providers (psychiatrists and psychologists). Feasibility, usability, acceptability, and user satisfaction were measured. Results: This study was performed with 39 patients with TRS. The dropout rate was 18% (7/39), the main reasons being as follows: loss to follow-up, clinical worsening, physical discomfort of the smartwatch, and social stigma. Patients' acceptance of m-RESIST ranged from moderate to high. The m-RESIST intervention could provide better control of the illness and appropriate care, together with offering user-friendly and easy-to-use technology. In terms of user experience, patients indicated that m-RESIST enabled easier and quicker communication with clinicians and made them feel more protected and safer. Patients' satisfaction was generally good: 78% (25/32) considered the quality of service as good or excellent, 84% (27/32) reported that they would use it again, and 94% (30/32) reported that they were mostly satisfied. Conclusions: The m-RESIST project has provided the basis for a new modular program based on novel technology: the m-RESIST intervention. This program was well-accepted by patients in terms of acceptability, usability, and satisfaction. Our results offer an encouraging starting point regarding mHealth technologies for patients with TRS.This work has been supported by the Horizon 2020 Framework Programme of the European Union (grant 643552) and partly funded by CERCA (Centres de Recerca de Catalunya) Programme/Generalitat de Catalunya

Characteristics and predictors of off-label use of antipsychotics in general population sample

Objective Increasing number of people have been prescribed antipsychotics (APs) off-label in recent decades. This study aimed to identify the characteristics and predictors of receiving prescription of antipsychotics off-label. Methods The study sample was part of the Northern Finland Birth Cohort 1966 (n = 7071). Data included questionnaires and national register data. Information on prescribed medications was extracted from the national register. The sample was divided into three groups: Persons who had been prescribed APs off-label (n = 137), individuals with non-psychotic mental disorders without APs off label (n = 1478) and individuals who had been diagnosed with psychosis or bipolar disorder and who had been prescribed APs (n = 151). We compared sociodemographic, lifestyle and clinical characteristics between the off-label and the comparison groups using logistic regression. Results The most common diagnoses in the off-label group were depression (n = 96, 70.1%) and anxiety (n = 55, 40.1%). Compared with individuals with non-psychotic mental disorders who were not prescribed APs off-label, individuals with prescribed off-label APs had a lower level of education, lower socioeconomic status, were less often married, had a higher level of somatic and psychiatric morbidity, were more often smokers and more often had a substance abuse disorder and heavy alcohol consumption. When comparing the off-label group to individuals with psychosis or bipolar disorder who used APs, there were less differences, though individuals with psychosis or bipolar disorder had more markers of morbidity and a lower level of education. Conclusion Individuals who had been prescribed APs off label had a higher level of mental and somatic morbidity and poorer socioeconomic status than individuals with non-psychotic mental disorders who did not use APs.Peer reviewe

Intensity of artefacts in cone beam CT examinations caused by titanium and glass fibre-reinforced composite implants

Objectives:The aim was to compare titanium and glass fibre-reinforced composite (FRC) orbital floor implants using cone beam CT (CBCT). FRC implants are nonmetallic and these implants have not been analysed in CBCT images before. The purpose of this study is to compare the artefact formation of the titanium and the FRC orbital floor implants in CBCT images.Methods:One commercially pure titanium and one S-glass FRC with bioactive glass particles implant were imaged with CBCT using the same imaging values (80 kV, 1 mA, FOV 60 × 60 mm). CBCT images were analysed in axial slices from three areas to determine the magnitude of the artefacts in the vicinity of the implants. Quantified results based on the gray values of images were analysed using analysis-of-variance.Results:Compared to the reference the gray values of the titanium implant are more negative in every region of interest in all slices (p Conclusions:The titanium implant caused artefacts in all of the analysed CBCT slices. Compared to the reference the gray values of the FRC implant changed only slightly and this feature enables to use wider imaging options postoperatively

Association between changes in lumbar Modic changes and low back symptoms over a two-year period

Background: The association of Modic changes (MC) with low back pain (LBP) is unclear. The purpose of our study was to investigate the associations between the extent of Type 1 (M1) and Type 2 (M2) MC and low back symptoms over a two-year period. Methods: The subjects (n = 64, mean age 43.8 y; 55 [86%] women) were consecutive chronic LBP patients who had M1 or mixed M1/M2 on lumbar spine magnetic resonance imaging (MRI). Size and type of MC on sagittal lumbar MRI and clinical data regarding low back symptoms were recorded at baseline and two-year follow-up. The size (%) of each MC in relation to vertebral size was estimated from sagittal slices (midsagittal and left and right quarter), while proportions of M1 and M2 within the MC were evaluated from three separate slices covering the MC. The extent (%) of M1 and M2 was calculated as a product of the size of MC and the proportions of M1 and M2 within the MC, respectively. Changes in the extent of M1 and M2 were analysed for associations with changes in LBP intensity and the Oswestry disability index (ODI), using linear regression analysis. Results: At baseline, the mean LBP intensity was 6.5 and the mean ODI was 33%. During follow-up, LBP intensity increased in 15 patients and decreased in 41, while ODI increased in 19 patients and decreased in 44. In univariate analyses, change in the extent of M1 associated significantly positively with changes in LBP intensity and ODI (beta 0.26, p = 0.036 and beta 0.30, p = 0.017; respectively), whereas the change in the extent of M2 did not associate with changes in LBP intensity and ODI (beta -0.24, p = 0.054 and beta -0.13, p = 0.306; respectively). After adjustment for age, gender, and size of MC at baseline, change in the extent of M1 remained significantly positively associated with change in ODI (beta 0.53, p = 0.003). Conclusion: Change in the extent of M1 associated positively with changes in low back symptoms.Peer reviewe

Prevalence and characteristics of psychiatric morbidity treated in specialized health care in a nationwide cohort of people with newly diagnosed Alzheimer's disease

Objective: Psychiatric disorders have been implied as both risk factors and prodromal symptoms of Alzheimer's disease (AD). A better understanding of the history of psychiatric morbidity in people with AD may aid with understanding this relationship and highlight challenges in diagnosing AD in people with concomitant psychiatric disorders.Methods: Medication use and Alzheimer's disease (MEDALZ) study is a nationwide register-based cohort of people (n = 70,718) who received a clinically verified AD diagnosis in Finland in 2005-2011 and were community-dwelling at the time of diagnosis. The study population was divided into four groups based on psychiatric morbidity treated in specialized health care. We characterized the groups using data of psychiatric and somatic illnesses, psychotropic drug use, and socioeconomic factors and investigated factors associated with prodromal AD.Results: Altogether, 4.3% of cohort members had a psychiatric diagnosis at least five years before AD diagnosis, 3.1% had a psychiatric diagnosis only up to five years before AD diagnosis, and 1.1% had a psychiatric diagnosis both less and more than 5 years before AD. Belonging to the Prodromal group (psychiatric diagnosis within 5 years before AD diagnosis) was most strongly associated with substance abuse (RR 65.06, 95%CI 55.54-76.22). Other associated factors with the Prodromal group were female gender, use of psychotropics, stroke, and asthma/COPD.Conclusion: Substance abuse and psychotropic drug use are common five years before AD diagnosis. These can be potential markers of possible prodromal symptoms of AD and should be acknowledged in clinical work.</p

Off-label prescribing of antipsychotics - a questionnaire survey of Finnish physicians

English abstract.Peer reviewe

Kysely lääkäreille : psykoosilääkkeiden off label - määräämisen käytännöt

Unettomuus ja ahdistuneisuus olivat yleisimmät syyt, joiden takia lääkärit määräsivät psykoosilääkkeitä off label -käyttöön. Eniten määrättiin ketiapiinia. Lääkärit raportoivat potilaiden saavan off label -käytöstä enemmän hyötyä kuin haittaa. Potilaiden seurantaan tulee kiinnittää nykyistä enemmän huomiota

Longitudinal regional brain volume loss in schizophrenia: Relationship to antipsychotic medication and change in social function.

BACKGROUND: Progressive brain volume loss in schizophrenia has been reported in previous studies but its cause and regional distribution remains unclear. We investigated progressive regional brain reductions in schizophrenia and correlations with potential mediators. METHOD: Participants were drawn from the Northern Finland Birth Cohort 1966. A total of 33 schizophrenia individuals and 71 controls were MRI scanned at baseline (mean age=34.7, SD=0.77) and at follow-up (mean age=43.4, SD=0.44). Regional brain change differences and associations with clinical mediators were examined using FSL voxelwise SIENA. RESULTS: Schizophrenia cases exhibited greater progressive brain reductions than controls, mainly in the frontal and temporal lobes. The degree of periventricular brain volume reductions were predicted by antipsychotic medication exposure at the fourth ventricular edge and by the number of days in hospital between the scans (a proxy measure of relapse duration) at the thalamic ventricular border. Decline in social and occupational functioning was associated with right supramarginal gyrus reduction. CONCLUSION: Our findings are consistent with the possibility that antipsychotic medication exposure and time spent in relapse partially explain progressive brain reductions in schizophrenia. However, residual confounding could also account for the findings and caution must be applied before drawing causal inferences from associations demonstrated in observational studies of modest size. Less progressive brain volume loss in schizophrenia may indicate better preserved social and occupational functions.Academy of Finland, Medical Research Council, Sigrid Jusélius Foundation and the Signe and Ane Gyllenberg Foundation, Finland, Stanley Foundation, Brain & Behavior Research Foundation. The work was partially completed within the University of Cambridge Behavioural and Clinical Neuroscience Institute, supported by a joint award from the Medical Research Council and Wellcome Trust.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.schres.2015.06.01