Cognitive Underperformance in a Mixed Neuropsychiatric Sample at Diagnostic Evaluation of Adult ADHD.

(1) Background: The clinical assessment of attention-deficit/hyperactivity disorder (ADHD) in adulthood is known to show non-trivial base rates of noncredible performance and requires thorough validity assessment. (2) Objectives: The present study estimated base rates of noncredible performance in clinical evaluations of adult ADHD on one or more of 17 embedded validity indicators (EVIs). This study further examines the effect of the order of test administration on EVI failure rates, the association between cognitive underperformance and symptom overreporting, and the prediction of cognitive underperformance by clinical information. (3) Methods: A mixed neuropsychiatric sample (N = 464, ADHD = 227) completed a comprehensive neuropsychological assessment battery on the Vienna Test System (VTS; CFADHD). Test performance allows the computation of 17 embedded performance validity indicators (PVTs) derived from eight different neuropsychological tests. Further, all participants completed several self- and other-report symptom rating scales assessing depressive symptoms and cognitive functioning. The Conners' Adult ADHD Rating Scale and the Beck Depression Inventory-II were administered to derive embedded symptom validity measures (SVTs). (4) Results and conclusion: Noncredible performance occurs in a sizeable proportion of about 10% up to 30% of individuals throughout the entire battery. Tests for attention and concentration appear to be the most adequate and sensitive for detecting underperformance. Cognitive underperformance represents a coherent construct and seems dissociable from symptom overreporting. These results emphasize the importance of performing multiple PVTs, at different time points, and promote more accurate calculation of the positive and negative predictive values of a given validity measure for noncredible performance during clinical assessments. Future studies should further examine whether and how the present results stand in other clinical populations, by implementing rigorous reference standards of noncredible performance, characterizing those failing PVT assessments, and differentiating between underlying motivations.

Cancer Patients' Age-Related Benefits from Mobile Neurofeedback-Therapy in Quality of Life and Self-efficacy: A Clinical Waitlist Control Study.

Electroencephalographic neurofeedback (EEG NF) can improve quality of life (QoL) and reduce distress by modifying the amplitude of selected brain frequencies. This study aims to investigate the effects of NF therapy on QoL and self-efficacy in cancer patients and to explore age-related reactions. In a waitlist control paradigm, psychometric data (EORTC QLQ-C30, General Self-Efficacy Scale) of 20 patients were collected at three different time points, each five weeks apart. An outpatient 10-session NF intervention (mobile) was conducted between the second and third measurement point. QoL and self-efficacy changed significantly over time (QoL: F(2,36) = 5.294, p < .05, η2 = .227; Self-efficacy: F(2,26) = 8.178, p < .05, η2 = .386). While QoL increased in younger patients, older patients initially showed a decrease in QoL, which then increased during intervention. Younger patients did not differ from older patients in QoL in both waitlist control (T0-T1) and intervention phase (T1-T2). QoL in older patients significantly differed between waitlist control and intervention phase (Z = - 2.023, p < .05, d = 1.085). Self-efficacy increased in both age categories. Younger and older patients did not differ in self-efficacy in waitlist control, but in intervention phase (F(1,16) = 7.014, p < .05, η2 = .319). The current findings suggest that NF therapy is a promising treatment modality for improving QoL in cancer patients. Our study reveals NF being a tool to influence self-efficacy, which should receive more appreciation in clinical care. However, the effect of NF in different age groups as well as the influence on further cancer-related symptoms should be investigated in future research.

Networks of Neuropsychological Functions in the Clinical Evaluation of Adult ADHD.

This study applied network analysis to explore the relations between neuropsychological functions of individuals in the clinical evaluation of attention-deficit/hyperactivity disorder (ADHD) in adulthood. A total of 319 participants from an outpatient referral context, that is, 173 individuals with ADHD (ADHD group) and 146 individuals without ADHD (n-ADHD group), took part in this study and completed a comprehensive neuropsychological assessment. A denser network with stronger global connectivity was observed in the ADHD group compared to the n-ADHD group. The strongest connections were consistent in both networks, that is, the connections between selective attention and vigilance, and connections between processing speed, fluency, and flexibility. Further centrality estimation revealed attention-related variables to have the highest expected influence in both networks. The observed relationships between neuropsychological functions, and the high centrality of attention, may help identify neuropsychological profiles that are specific to ADHD and optimize neuropsychological assessment and treatment planning of individuals with cognitive impairment.

Ceramide levels in blood plasma correlate with major depressive disorder severity and its neutralization abrogates depressive behavior in mice.

Major depressive disorder (MDD) is a severe disease of unknown pathogenesis that will affect ∼10% of people during their lifetime. Therapy for MDD requires prolonged treatment and often fails, predicating a need for novel treatment strategies. Here, we report increased ceramide levels in the blood plasma of MDD patients and in murine stress-induced models of MDD. These blood plasma ceramide levels correlated with the severity of MDD in human patients and were independent of age, sex, or body mass index. In addition, intravenous injection of anti-ceramide antibodies or neutral ceramidase rapidly abrogated stress-induced MDD, and intravenous injection of blood plasma from mice with MDD induced depression-like behavior in untreated mice, which was abrogated by ex vivo preincubation of the plasma with anti-ceramide antibodies or ceramidase. Mechanistically, we demonstrate that ceramide accumulated in endothelial cells of the hippocampus of stressed mice, evidenced by the quantitative measurement of ceramide in purified hippocampus endothelial cells. We found ceramide inhibited the activity of phospholipase D (PLD) in endothelial cells in vitro and in the hippocampus in vivo and thereby decreased phosphatidic acid in the hippocampus. Finally, we show intravenous injection of PLD or phosphatidic acid abrogated MDD, indicating the significance of this pathway in MDD pathogenesis. Our data indicate that ceramide controls PLD activity and phosphatidic acid formation in hippocampal endothelial cells and thereby mediates MDD. We propose that neutralization of plasma ceramide could represent a rapid-acting targeted treatment for MDD.

It Takes Time: Vigilance and Sustained Attention Assessment in Adults with ADHD.

Objectives: The present study compares the utility of eight different tests of vigilance and sustained attention in the neuropsychological examination of adults with Attention-deficit/hyperactivity disorder (ADHD). Methods: Thirty-one adults diagnosed with ADHD performed eight tests for vigilance and sustained attention, spread over three assessment days. Results: Adults with ADHD showed cognitive impairments in most tests and test variables, even though their sensitivity differed greatly. No specific type of test variable stands out to be the most sensitive, and no evidence for a differential deterioration of performance over time was observed. Conclusion: This study underscores the role of vigilance and sustained attention tests in the assessment of adult ADHD. It is further concluded that summary scores over the entire test duration are sufficient, but that all variables of a test should be considered. Finally, we hypothesize that reassessment on a different day may benefit a more accurate clinical assessment of adults with ADHD, in order to adequately take intraindividual fluctuations and limitations regarding test reliability into account.

Klotho KL-VS haplotype does not improve cognition in a population-based sample of adults age 55-87 years.

The heterozygous human Klotho KL-VS haplotype has been associated with improved cognitive performance but results are inconsistent. Here we assessed Klotho KL-VS haplotype and cognition using data from the third examination of the population-based Heinz Nixdorf Recall Study. We analyzed cognition tests (immediate and delayed word list, Trail-Making Test [TMT] part A and B, Maze test, interference condition of the Stroop color-word test, verbal fluency) and their associations with Klotho KL-VS haplotype. The Klotho KL-VS haplotype is classified by the V-allele at SNP rs9536314 (F352V) and the S-allele at SNP rs9527025 (C370S). Heterozygotes for the KL-VS haplotype were compared with non-carriers. Analyses were performed in 1812 subjects (55-87 years). We found consistent but only slightly lower performance in heterozygous carriers of the KL-VS haplotype in all tasks with Z-scores ranging between Z = - 0.042 (verbal fluency) and - 0.17 (TMT part A). Differences between carriers and non-carriers were similar for men and women for all tests but TMT part B (interaction contrast = 8.4 s (95% CI - 2.3; 19.1)). While cognition declined with age, we found an effect modification by age (55-65 years, 66-75 years, > 75 years). In the 66-75 years KL-VS heterozygous age group, lower performance was seen in memory, visual attention and motor speed. Contrary to our hypothesis, heterozygous carriers of the KL-VS haplotype did not show enhanced performance in cognitive tests in our study.

Accuracy and reproducibility of automated white matter hyperintensities segmentation with lesion segmentation tool: A European multi-site 3T study.

Brain vascular damage accumulate in aging and often manifest as white matter hyperintensities (WMHs) on MRI. Despite increased interest in automated methods to segment WMHs, a gold standard has not been achieved and their longitudinal reproducibility has been poorly investigated. The aim of present work is to evaluate accuracy and reproducibility of two freely available segmentation algorithms. A harmonized MRI protocol was implemented in 3T-scanners across 13 European sites, each scanning five volunteers twice (test-retest) using 2D-FLAIR. Automated segmentation was performed using Lesion segmentation tool algorithms (LST): the Lesion growth algorithm (LGA) in SPM8 and 12 and the Lesion prediction algorithm (LPA). To assess reproducibility, we applied the LST longitudinal pipeline to the LGA and LPA outputs for both the test and retest scans. We evaluated volumetric and spatial accuracy comparing LGA and LPA with manual tracing, and for reproducibility the test versus retest. Median volume difference between automated WMH and manual segmentations (mL) was -0.22[IQR = 0.50] for LGA-SPM8, -0.12[0.57] for LGA-SPM12, -0.09[0.53] for LPA, while the spatial accuracy (Dice Coefficient) was 0.29[0.31], 0.33[0.26] and 0.41[0.23], respectively. The reproducibility analysis showed a median reproducibility error of 20%[IQR = 41] for LGA-SPM8, 14% [31] for LGA-SPM12 and 10% [27] with the LPA cross-sectional pipeline. Applying the LST longitudinal pipeline, the reproducibility errors were considerably reduced (LGA: 0%[IQR = 0], p < 0.001; LPA: 0% [3], p < 0.001) compared to those derived using the cross-sectional algorithms. The DC using the longitudinal pipeline was excellent (median = 1) for LGA [IQR = 0] and LPA [0.02]. LST algorithms showed moderate accuracy and good reproducibility. Therefore, it can be used as a reliable cross-sectional and longitudinal tool in multi-site studies.

Problems in measuring the JTC-bias in patients with psychotic disorders with the fish task: a secondary analysis of a baseline assessment of a randomized controlled trial.

BACKGROUND: The jumping to conclusions bias (JTC) is considered to be an important causal factor in theoretical models for the formation and maintenance of delusions. However, recent meta-analytic findings show a rather equivocal pattern of results regarding associations between JTC and delusions. Thus, the present study aims to investigate in a large sample whether the JTC-bias is more pronounced in patients with psychotic disorders in comparison to controls and whether the JTC bias is associated with a more severe delusional conviction, persecutory delusions, and positive symptoms in general. METHODS: Patients with psychotic disorders (n = 300) enrolled in a therapy trial and healthy controls (n = 51) conducted a variant of the beads task (fish task) as a measure for the JTC-bias at the start of the trial. Further, clinical interviews were used to assess patients' delusional severity and delusional conviction. RESULTS: There were no statistically significant differences between patients with psychotic disorders (with 53% displaying the JTC-bias) and controls (41%). Furthermore, there were no statistically significant correlations between JTC measures and persecutory delusions, delusional conviction, and positive symptoms. CONCLUSIONS: We found no differences in JTC between patients with psychotic disorders and healthy controls, which is in part in line with meta-analytic findings using a wide range of JTC task variants. Interestingly, patients with psychotic disorders displayed JTC rates commonly found in the literature, while healthy control subjects showed an unexpectedly high level of JTC. The task variant we used in the present study (fish task) is discussed as a potential reason for our results, as it may induce a more deliberative reasoning style in controls as compared to the traditional beads task. Furthermore, possible implications for the measurement of the JTC-bias, in general, are discussed. TRIAL REGISTRATION: ISRCTN29242879 ( isrctn.com ), date of registration: April 12th 2006, retrospectively registered.

Amygdalar nuclei and hippocampal subfields on MRI: Test-retest reliability of automated volumetry across different MRI sites and vendors.

BACKGROUND: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults. METHODS: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. RESULTS: Significant MRI site and vendor effects (p â€‹< â€‹.05) were found in a few subfields/nuclei for the ε, while extensive effects were found for the DICE score of most subfields/nuclei. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (absolute value of Spearman's r correlations >0.43, p â€‹< â€‹1.39E-36). In particular, volumes larger than 200 â€‹mm3 (for amygdalar nuclei) and 300 â€‹mm3 (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε â€‹< â€‹5% and DICE â€‹> â€‹0.80). CONCLUSION: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.

Theory of mind, emotion recognition, delusions and the quality of the therapeutic relationship in patients with psychosis - a secondary analysis of a randomized-controlled therapy trial.

BACKGROUND: Cognitive models of psychosis postulate an important role of Theory of mind (ToM) in the formation and maintenance of delusions, but research on this plausible conjecture has gathered conflicting findings. In addition, it is still an open question whether problems in emotion recognition (ER) are associated with delusions. We examined the association of problems in ToM and ER with different aspects of delusions in a large sample of patients with psychosis enrolled in a therapy trial. This also enabled us to explore the possible impact of ToM and ER on one part of patients' social life: the quality of their therapeutic relationship. METHODS: Patients with psychotic disorders and delusions and/or hallucinations (n = 185) and healthy controls (n = 48) completed a ToM picture sequencing task and an ER task. Subsequently, patients were enrolled in a randomized-controlled Cognitive Behavior Therapy (CBT) trial (ISRCTN29242879). Patients and therapists rated the quality of the therapeutic relationship during the first five sessions of therapy. RESULTS: In comparison to controls, patients were impaired in both ToM and ER. Patients with deficits in ER experienced more severe delusional distress, whereas ToM problems were not related to delusions. In addition, deficits in ER predicted a less favorable therapeutic relationship and interactional problems viewed by the therapist. Impaired ER also moderated (increased) the negative influence of delusions on the therapeutic relationship and interactional difficulties viewed by the therapist. CONCLUSIONS: Cognitive models on the formation and maintenance of delusions should consider ER as a potential candidate that might be related to the formation and maintenance of delusional distress, whereas problems in ToM might not be directly related to delusions and secondary dimensions of delusions. In addition, problems in ER in patients with psychosis might have an impact on the quality of the therapeutic relationship and patients with problems in ER are more likely to be viewed as problematic by their therapists. Nevertheless, training ER might be a way to improve the quality of the therapeutic relationship and potentially the effectiveness of CBT or other interventions for patients with psychosis.

Cognitive bias modification as an add-on treatment in clinical depression: Results from a placebo-controlled, single-blinded randomized control trial.

BACKGROUND: Only 60% of depressed patients respond sufficiently to treatment, so there is a dire need for novel approaches to improve treatment effects. Cognitive Bias Modification (CBM) may be an effective and easily implemented computerized add-on to treatment-as-usual. Therefore, we investigated the effects of a positivity-attention training and a positivity-approach training compared to control trainings. METHODS: In a blinded randomized-controlled design, 139 depressed inpatients received either the CBM Attention Dot-Probe Training (DPT) or the CBM Approach-Avoidance Training (AAT), next to treatment as usual. N = 121 finished all four training sessions. Both trainings had an active and a control condition. In both active conditions, patients were trained to preferentially process generally positive pictures over neutral pictures. Depressive symptom severity was assessed before and after CBM, and positivity bias was measured at the start and end of each session. RESULTS: Clinician-rated depressive symptom severity decreased more in patients who received the active condition of the DPT or the AAT compared to patients in the control conditions. Significant change in positivity bias was found for the DPT (not the AAT), but did not mediate the effect of the training on depressive symptoms. CONCLUSIONS: The results suggest that both types of CBM (i.e., DPT and AAT) may provide a fitting add-on treatment option for clinical depression. The working mechanisms and optimal dose of CBM trainings, plus their possible combination, should be examined in more detail.

Negative schemata about the self and others and paranoid ideation in at-risk states and those with persisting positive symptoms.

BACKGROUND: The objective of this study is to test the conflicting theories concerning the association of negative self and other schemata and paranoid ideation. METHODS: A risk-based approach, including risk stratification, is used to gain insight into the association of the negative self and other schemata that may be shared by individuals or differentiate between individuals at clinical high risk (CHR) for a first-episode psychosis and those with full-blown psychosis. The dataset includes a sample of individuals at CHR (n = 137) and a sample of individuals with persisting positive symptoms (PPS, n = 211). The CHR sample was subdivided according to a prognostic index yielding 4 CHR sub-classes with increasing risk for transition to psychosis. RESULTS: Negative beliefs about the self were associated with paranoid ideation in CHR and a lower risk state. In the highest risk state and full-blown psychosis, there is an association with negative beliefs about others. CONCLUSION: These findings are in line with theories suggesting a switch from a predominantly activated negative self-schema to a malevolent others-schema in association with paranoid ideation along the risk-continuum. However, due to methodological limitations these results should be replicated by future studies.

Neural Mechanisms Underlying Affective Theory of Mind in Violent Antisocial Personality Disorder and/or Schizophrenia.

Among violent offenders with schizophrenia, there are 2 sub-groups, one with and one without, conduct disorder (CD) and antisocial personality disorder (ASPD), who differ as to treatment response and alterations of brain structure. The present study aimed to determine whether the 2 groups also differ in Theory of Mind and neural activations subsuming this task. Five groups of men were compared: 3 groups of violent offenders-schizophrenia plus CD/ASPD, schizophrenia with no history of antisocial behavior prior to illness onset, and CD/ASPD with no severe mental illness-and 2 groups of non-offenders, one with schizophrenia and one without (H). Participants completed diagnostic interviews, the Psychopathy Checklist Screening Version Interview, the Interpersonal Reactivity Index, authorized access to clinical and criminal files, and underwent functional magnetic resonance imaging while completing an adapted version of the Reading-the-Mind-in-the-Eyes Task (RMET). Relative to H, nonviolent and violent men with schizophrenia and not CD/ASPD performed more poorly on the RMET, while violent offenders with CD/ASPD, both those with and without schizophrenia, performed similarly. The 2 groups of violent offenders with CD/ASPD, both those with and without schizophrenia, relative to the other groups, displayed higher levels of activation in a network of prefrontal and temporal-parietal regions and reduced activation in the amygdala. Relative to men without CD/ASPD, both groups of violent offenders with CD/ASPD displayed a distinct pattern of neural responses during emotional/mental state attribution pointing to distinct and comparatively successful processing of social information.

Association between CSF biomarkers, hippocampal volume and cognitive function in patients with amnestic mild cognitive impairment (MCI).

Few studies have examined the relationship between CSF and structural biomarkers, and cognitive function in MCI. We examined the relationship between cognitive function, hippocampal volume and cerebrospinal fluid (CSF) Aß42 and tau in 145 patients with MCI. Patients were assessed on cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), the Geriatric Depression Scale and the Functional Activities Questionnaire. Hippocampal volume was measured using magnetic resonance imaging (MRI), and CSF markers of Aß42, tau and p-tau181 were also measured. Worse performance on a wide range of memory and sustained attention tasks were associated with reduced hippocampal volume, higher CSF tau and p-tau181 and increased tau/Aß42 ratio. Memory tasks were also associated with lower ability to conduct functional activities of daily living, providing a link between AD biomarkers, memory performance and functional outcome. These results suggest that biomarkers of Aß and tau are strongly related to cognitive performance as assessed by the CANTAB, and have implications for the early detection and characterization of incipient AD.

Attenuated Readiness Potential in the Absence of Executive Dysfunction in Adults With ADHD.

OBJECTIVE: Patients with ADHD display a decreased contingent negative variation in Go/NoGo tasks. It is unclear whether the attenuation is due to deficits of executive function or to disorder of motor planning. The readiness potential (RP) recorded during self-initiated movements could cast light on this question. METHOD: RP was recorded in 25 stably medicated adult ADHD patients and 21 healthy controls matched for age, education, and verbal IQ. Participants also completed neuropsychological tests of executive function. RESULTS: Compared with healthy controls, ADHD patients showed significantly diminished RP peaks and also decreased negativity in preparation of the movement at frontal locations. There were no significant group differences with regard to tests of executive function. CONCLUSION: In adults with ADHD, deficits of motor organization are also manifest in situations not involving external stimulus processing. The attenuated RP occurred in the absence of executive dysfunction. Results are consistent with partial independence between motor and executive dysfunction in ADHD.

The effect of auditory and visual training on the mismatch negativity in schizophrenia.

BACKGROUND: The mismatch negativity (MMN) is an electrophysiological index of early auditory attention and has repeatedly been suggested to be associated with cognitive functioning. Despite the frequently reported finding of reduced MMN amplitude in schizophrenia, up to now, studies assessing the impact of perceptual discrimination training aiming to improve MMN measures in schizophrenia patients are scarce. METHOD: In the present study, the effect of auditory training (AUD, n=14) on the MMN was compared to that of visual-spatial training (VIS, n=14) and a treatment-as-usual (TAU, n=14) condition in schizophrenia patients. Training consisted of ten 50-min sessions over two weeks. Assessments took place before and after training and at a two-month follow-up. They comprised clinical measures and MMN recordings to frequency and duration deviant stimuli. RESULTS: There was a significant main effect for type of stimulus deviance with a more negative MMN to frequency than duration deviants. In contrast to our hypotheses, we did not find training specific effects on MMN amplitude or latency. CONCLUSION: The visual, as well as the auditory training program failed to result in treatment related MMN changes in schizophrenia patients when compared to treatment-as-usual as a control condition. In contrast to reports in healthy subjects, the induction of training related MMN changes in schizophrenia patients may constitute a specific challenge and require more extensive training protocols.

Occipital event-related potentials to addiction-related stimuli in detoxified patients with alcohol dependence, and their association with three-month relapse.

BACKGROUND: Understanding the biological underpinnings of relapse in alcohol dependency is a major issue in addiction research. Based on recent evidence regarding the relevance of occipital visual evoked response potentials (ERPs) in addiction research, and its significance for relapse research, we assessed occipital ERPs to alcohol- and non-alcohol-related stimuli in recently detoxified patients and controls. METHODS: Thirty recently detoxified patients with alcohol addiction, and 31 healthy control subjects, were assessed in a Go and a NoGo condition, each using three visual stimuli: tea, juice and beer. In the "Go" condition, subjects had to respond to the juice (12.5 %) and the beer stimulus (12.5 %), and ignore the tea picture (75 %). In the "NoGo" condition, subjects had to respond to the tea picture (75 %) and ignore the juice and the beer picture (12.5 % each). The subjects' EEGs were analyzed with regard to the occipital P100 and N170 ERP components. Patients were then evaluated for relapse 3 months after this initial assessment. RESULTS: P100 amplitudes differed between conditions and between stimuli, and we found a condition x electrode interaction. However, none of these P100 results involved group or relapse-status effects. N170 amplitudes in patients were elevated as compared to controls. Additionally, patients' heightened N170 amplitudes in response to the alcohol-related (beer) stimulus were found only under the NoGo condition, where subjects had to react to the frequent tea stimulus and ignore the beer and the juice stimuli, thus resulting in a condition x stimulus x group interaction. Patients reporting relapse in a 3-month follow-up assessment showed larger NoGo N170 alcohol cue-related ERP amplitudes and increased depression scores as compared to patients who stayed abstinent. Depression was related to shortened P100 latencies in patients, but unrelated to the N170 NoGo cue-reactivity effect. CONCLUSIONS: Our results indicate a sensitivity of occipital ERPs to addiction-related stimuli when these act as non-targets. Recently detoxified patients may be vulnerable to addiction-related cues when these occur outside the focus of directed attention, thereby circumventing intentional control processes. Furthermore, ERPs to addiction-related stimuli may be useful as a predictor of abstinence success in recently detoxified patients.

Test-retest reliability of the default mode network in a multi-centric fMRI study of healthy elderly: Effects of data-driven physiological noise correction techniques.

Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within-site test-retest reliability and the across-site reproducibility consistency of DMN-derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue-based regression, PESTICA and FSL-FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z-scores and, albeit less markedly, the cluster-size in the DMN; in particular, FSL-FIX tended to increase the DMN z-scores compared to others. Within-site test-retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5-11% for DMN z-scores and cluster-size reliability. DMN pattern overlap was in the range 60-65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL-FIX and Tissue-based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z-scores relative to NPC. Overall these findings support the use of rPNC methods like tissue-based or FSL-FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114-2132, 2016. © 2016 Wiley Periodicals, Inc.

The effect of deviance predictability on mismatch negativity in schizophrenia patients.

Mismatch negativity (MMN) is an electrophysiological index of prediction error processing and recently has been considered an endophenotype marker in schizophrenia. While the prediction error is a core concept in the MMN generation, predictability of deviance occurrence has rarely been assessed in MMN research and in schizophrenia patients. We investigated the MMN to 12% temporally predictable or unpredictable duration decrement deviant stimuli in two runs in 29 healthy controls and 31 schizophrenia patients. We analyzed MMN amplitudes and latencies and its associations with clinical symptoms at electrode Fz. With a stimulus onset asynchronicity of 500 ms in the regular predictable condition, a deviant occurred every 4s while it varied randomly in the unpredictable condition. In the random condition we found diminished MMN amplitudes in patients which normalized in the regular deviance condition, resulting in an analysis of variance main effect of predictability and a predictability x group interaction. Deviance predictability did not affect the MMN of control subjects and we found no relevant results with regard to MMN latencies. Our results indicate that MMN amplitudes in patients normalize to the level of the control subjects in the case of a temporally fixed regular deviant. In schizophrenia patients the detection of deviance is basically intact. However, the temporal uncertainty of deviance occurrence may be of substantial relevance to the highly replicated MMN deficit in schizophrenia patients.

Aerobic Activity in the Healthy Elderly Is Associated with Larger Plasticity in Memory Related Brain Structures and Lower Systemic Inflammation.

Cognitive abilities decline over the time course of our life, a process, which may be mediated by brain atrophy and enhanced inflammatory processes. Lifestyle factors, such as regular physical activities have been shown to counteract those noxious processes and are assumed to delay or possibly even prevent pathological states, such as dementing disorders. Whereas the impact of lifestyle and immunological factors and their interactions on cognitive aging have been frequently studied, their effects on neural parameters as brain activation and functional connectivity are less well studied. Therefore, we investigated 32 healthy elderly individuals (60.4 ± 5.0 SD; range 52-71 years) with low or high level of self-reported aerobic physical activity at the time of testing. A higher compared to a lower level in aerobic physical activity was associated with an increased encoding related functional connectivity in an episodic memory network comprising mPFC, thalamus, hippocampus precuneus, and insula. Moreover, encoding related functional connectivity of this network was associated with decreased systemic inflammation, as measured by systemic levels of interleukin 6.