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We performed a meta-analysis to synthesize evidence on the efficacy and safety of physical exercise as an add-on therapeutic intervention for quality of life (QoL), depressive symptoms and cognition across six chronic brain disorders: Alzheimer's disease, Huntington's disease, multiple sclerosis, Parkinson's disease, schizophrenia and unipolar depression. 122 studies ( = k) (n = 7231) were included. Exercise was superior to treatment as usual in improving QoL (k = 64, n = 4334, ES = 0.40, p < 0.0001), depressive symptoms (k = 60, n = 2909, ES = 0.78, p < 0.0001), the cognitive domains attention and working memory (k = 21, n = 1313, ES = 0.24, p < 0.009), executive functioning (k = 14, n = 977, ES = 0.15, p = 0.013), memory (k = 12, n = 994, ES = 0.12, p = 0.038) and psychomotor speed (k = 16, n = 896, ES = 0.23, p = 0.003). Meta-regression showed a dose-response effect for exercise time (min/week) on depressive symptoms (β = 0.007, p = 0.012). 69% of the studies that reported on safety, found no complications. Exercise is an efficacious and safe add-on therapeutic intervention showing a medium-sized effect on QoL and a large effect on mood in patients with chronic brain disorders, with a positive dose-response correlation. Exercise also improved several cognitive domains with small but significant effects.

Hallucinations may arise from an imbalance between sensory and higher cognitive brain regions, reflected by alterations in functional connectivity. It is unknown whether hallucinations across the psychosis continuum exhibit similar alterations in functional connectivity, suggesting a common neural mechanism, or whether different mechanisms link to hallucinations across phenotypes. We acquired resting-state functional MRI scans of 483 participants, including 40 non-clinical individuals with hallucinations, 99 schizophrenia patients with hallucinations, 74 bipolar-I disorder patients with hallucinations, 42 bipolar-I disorder patients without hallucinations, and 228 healthy controls. The weighted connectivity matrices were compared using network-based statistics. Non-clinical individuals with hallucinations and schizophrenia patients with hallucinations exhibited increased connectivity, mainly among fronto-temporal and fronto-insula/cingulate areas compared to controls (P < 0.001 adjusted). Differential effects were observed for bipolar-I disorder patients with hallucinations versus controls, mainly characterized by decreased connectivity between fronto-temporal and fronto-striatal areas (P = 0.012 adjusted). No connectivity alterations were found between bipolar-I disorder patients without hallucinations and controls. Our results support the notion that hallucinations in non-clinical individuals and schizophrenia patients are related to altered interactions between sensory and higher-order cognitive brain regions. However, a different dysconnectivity pattern was observed for bipolar-I disorder patients with hallucinations, which implies a different neural mechanism across the psychosis continuum.

To gain insight into possible underlying mechanism(s) of visual hallucinations (VH) in Parkinson's disease (PD), we explored changes in local oscillatory activity in different frequency bands with source-space magnetoencephalography (MEG). Eyes-closed resting-state MEG recordings were obtained from 20 PD patients with hallucinations (Hall+) and 20 PD patients without hallucinations (Hall-), matched for age, gender and disease severity. The Hall+ group was subdivided into 10 patients with VH only (unimodal Hall+) and 10 patients with multimodal hallucinations (multimodal Hall+). Subsequently, neuronal activity at source-level was reconstructed using an atlas-based beamforming approach resulting in source-space time series for 78 cortical and 12 subcortical regions of interest in the automated anatomical labeling (AAL) atlas. Peak frequency (PF) and relative power in six frequency bands (delta, theta, alpha1, alpha2, beta and gamma) were compared between Hall+ and Hall-, unimodal Hall+ and Hall-, multimodal Hall+ and Hall-, and unimodal Hall+ and multimodal Hall+ patients. PF and relative power per frequency band did not differ between Hall+ and Hall-, and multimodal Hall+ and Hall- patients. Compared to the Hall- group, unimodal Hall+ patients showed significantly higher relative power in the theta band (p = 0.005), and significantly lower relative power in the beta (p = 0.029) and gamma (p = 0.007) band, and lower PF (p = 0.011). Compared to the unimodal Hall+, multimodal Hall+ showed significantly higher PF (p = 0.007). In conclusion, a subset of PD patients with only VH showed slowing of MEG-based resting-state brain activity with an increase in theta activity, and a concomitant decrease in beta and gamma activity, which could indicate central cholinergic dysfunction as underlying mechanism of VH in PD. This signature was absent in PD patients with multimodal hallucinations., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

We studied neurophysiological indicators of hallucinations in Alzheimer's disease patients with hallucinations (ADhall+), and compared them with nonhallucinating AD (ADhall-) and dementia with Lewy bodies (DLBhall+) patients. Thirty-six matched ADhall+ and 108 ADhall- and 29 DLBhall+ patients were selected from the Amsterdam Dementia Cohort. Electroencephalography (EEG) spectral and functional connectivity (FC) analyses (phase lag index) were performed. Quantitative and visual EEG measures were combined in a random forest algorithm to determine which EEG-based variable(s) play a role in hallucinations. ADhall+ patients showed lower peak frequency (7.26 vs. 7.94 Hz, p < 0.01), α2-and β-power, and α2-FC but higher δ-power compared to ADhall-. ADhall+ showed lower δ-power, higher β-power, and α1-FC than DLBhall+ but did not differ in peak frequency (7.26 vs. 6.95 Hz), θ- or α-power. ADhall+ patients could be differentiated from ADhall- and DLBhall+ with a weighted accuracy of 71% with α1-power and 100% with β-FC, the 2 most differentiating features. In sum, EEG slowing and decrease in α1-and β-band activity form potential neurophysiological indicators of underlying cholinergic deficiency in ADhall+ and DLBhall+., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Averaging at 13.4%, current literature reports widely varying prevalence rates of hallucinations in patients with probable Alzheimer's disease (AD), and is still inconclusive on contributive factors to hallucinations in AD., Methods: This study assessed prevalence, associated factors and clinical characteristics of hallucinations in 1227 patients with probable AD, derived from a tertiary memory clinic specialized in early diagnosis of dementia. Hallucinations were assessed with the Neuropsychiatric Inventory., Results: Hallucination prevalence was very low, with only 4.5% (n = 55/1227) affected patients. Hallucinations were mostly visual (n = 40/55) or auditory (n = 12/55). Comorbid delusions were present in over one-third of cases (n = 23/55).Hallucinations were associated with increased dementia severity, neuropsychiatric symptoms, and a lifetime history of hallucination-evoking disease (such as depression and sensory impairment), but not with age or gender., Discussion: In the largest sample thus far, we report a low prevalence of hallucinations in probable AD patients, comparable to rates in non-demented elderly. Our results suggest that hallucinations are uncommon in early stage AD. Clinicians that encounter hallucinations in patients with early AD should be sensitive to hallucination-evoking comorbidity.

Introduction: The aim of this study was to build a random forest classifier to improve the diagnostic accuracy in differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and to quantify the relevance of multimodal diagnostic measures, with a focus on electroencephalography (EEG)., Methods: A total of 66 DLB, 66 AD patients, and 66 controls were selected from the Amsterdam Dementia Cohort. Quantitative EEG (qEEG) measures were combined with clinical, neuropsychological, visual EEG, neuroimaging, and cerebrospinal fluid data. Variable importance scores were calculated per diagnostic variable., Results: For discrimination between DLB and AD, the diagnostic accuracy of the classifier was 87%. Beta power was identified as the single-most important discriminating variable. qEEG increased the accuracy of the other multimodal diagnostic data with almost 10%., Discussion: Quantitative EEG has a higher discriminating value than the combination of the other multimodal variables in the differentiation between DLB and AD.

Background: Physical exercise may be valuable for patients with schizophrenia spectrum disorders as it may have beneficial effect on clinical symptoms, quality of life and cognition., Methods: A systematic search was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Controlled and uncontrolled studies investigating the effect of any type of physical exercise interventions in schizophrenia spectrum disorders were included. Outcome measures were clinical symptoms, quality of life, global functioning, depression or cognition. Meta-analyses were performed using Comprehensive Meta-Analysis software. A random effects model was used to compute overall weighted effect sizes in Hedges' g., Results: Twenty-nine studies were included, examining 1109 patients. Exercise was superior to control conditions in improving total symptom severity (k = 14, n = 719: Hedges' g = .39, P < .001), positive (k = 15, n = 715: Hedges' g = .32, P < .01), negative (k = 18, n = 854: Hedges' g = .49, P < .001), and general (k = 10, n = 475: Hedges' g = .27, P < .05) symptoms, quality of life (k = 11, n = 770: Hedges' g = .55, P < .001), global functioning (k = 5, n = 342: Hedges' g = .32, P < .01), and depressive symptoms (k = 7, n = 337: Hedges' g = .71, P < .001). Yoga, specifically, improved the cognitive subdomain long-term memory (k = 2, n = 184: Hedges' g = .32, P < .05), while exercise in general or in any other form had no effect on cognition., Conclusion: Physical exercise is a robust add-on treatment for improving clinical symptoms, quality of life, global functioning, and depressive symptoms in patients with schizophrenia. The effect on cognition is not demonstrated, but may be present for yoga., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Directed information flow between brain regions might be disrupted in dementia with Lewy bodies (DLB) and relate to the clinical syndrome of DLB. To investigate this hypothesis, resting-state electroencephalography recordings were obtained in patients with probable DLB and Alzheimer's disease (AD), and controls (N = 66 per group, matched for age and gender). Phase transfer entropy was used to measure directed connectivity in the groups for the theta, alpha, and beta frequency band. A posterior-to-anterior phase transfer entropy gradient, with occipital channels driving the frontal channels, was found in controls in all frequency bands. This posterior-to-anterior gradient was largely lost in DLB in the alpha band (p < 0.05). In the beta band, posterior brain regions were less driving in information flow in AD than in DLB and controls. In conclusion, the common posterior-to-anterior pattern of directed connectivity in controls is disturbed in DLB patients in the alpha band, and in AD patients in the beta band. Disrupted alpha band-directed connectivity may underlie the clinical syndrome of DLB and differentiate between DLB and AD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cerebral dominance of language function and hand preference are suggested to be heritable traits with possible shared genetic background. However, joined genetic studies of these traits have never been conducted. We performed a genetic linkage study in 37 multigenerational human pedigrees of both sexes (consisting of 355 subjects) enriched with left-handedness in which we also measured language lateralization. Hand preference was measured with the Edinburgh Handedness Inventory, and language lateralization was measured with functional transcranial Doppler during language production. The estimated heritability of left-handedness and language lateralization in these pedigrees is 0.24 and 0.31, respectively. A parametric major gene model was tested for left-handedness. Nonparametric analyses were performed for left-handedness, atypical lateralization, and degree of language lateralization. We did not observe genome-wide evidence for linkage in the parametric or nonparametric analyses for any of the phenotypes tested. However, multiple regions showed suggestive evidence of linkage. The parametric model showed suggestive linkage for left-handedness in the 22q13 region [heterogeneity logarithm of odds (HLOD) = 2.18]. Nonparametric multipoint analysis of left-handedness showed suggestive linkage in the same region [logarithm of odds (LOD) = 2.80]. Atypical language lateralization showed suggestive linkage in the 7q34 region (LODMax = 2.35). For strength of language lateralization, we observed suggestive linkage in the 6p22 (LODMax = 2.54), 7q32 (LODMax = 1.93), and 9q33 (LODMax = 2.10) regions. We did not observe any overlap of suggestive genetic signal between handedness and the extent of language lateralization. The absence of significant linkage argues against the presence of a major gene coding for both traits; rather, our results are suggestive of these traits being two independent polygenic complex traits., (Copyright © 2015 the authors 0270-6474/15/358730-07$15.00/0.)

Background and Purpose: Residual stenosis after recanalization of an acute symptomatic extracranial occlusion of the internal carotid artery (ICA) might be an indication for carotid endarterectomy. We evaluated the proportion of residual high-grade stenosis (≥70%, near occlusions not included) on follow-up imaging in a consecutive series of patients with an acute symptomatic occlusion of the extracranial ICA., Methods: We included patients participating in the Dutch Acute Stroke Study (DUST), who had an acute symptomatic occlusion of the extracranial ICA that was diagnosed on computed tomographic angiography within 9 hours after onset of neurological symptoms. Follow-up imaging of the carotid artery had to be available within 7 days after admission., Results: Of the 1021 patients participating in DUST between May 2009 and May 2013, an acute symptomatic occlusion of the extracranial ICA was found in 126 (12.3%) patients. Follow-up imaging was available in 86 (68.3%) of these patients. At follow-up, a residual stenosis of <30% was found in 15 (17.4%; 95% confidence interval, 10.8-26.9) patients, a 30% to 49% stenosis in 3 (3.5%; 95% confidence interval, 0.8-10.2) patients, a 50% to 69% stenosis in 2 (2.3%; 95% confidence interval, 0.1-8.6) patients, and a ≥70% stenosis in 14 (16.3%; 95% confidence interval, 9.8-25.6) patients. A near or persistent occlusion was present in the remaining 52 (60.5%) patients., Conclusions: A residual high-grade stenosis of the extracranial ICA occurs in 1 of 6 patients with a symptomatic occlusion in the acute stage of cerebral ischemia. Because this may have implications for secondary prevention, we recommend follow-up imaging in these patients within a week after the event., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00880113., (© 2014 American Heart Association, Inc.)

Background: Several Japanese studies have focused on identifying prognostic factors in patients with positive lymph nodes to predict recurrence rate and disease-free survival (DFS). However, different treatment protocol is followed in Japan compared with the European and American approach. This study was designed to investigate whether the number and/or location of lymph nodes predicts prognosis in patients with DTC treated with total thyroidectomy, lymph node dissection, and postoperative radioactive iodine ablation., Methods: All 402 patients who were treated at the Department of Nuclear Medicine between 1998 and 2010 for DTC were reviewed. Patients were treated with (near) total thyroidectomy, lymph node dissection on indication, and postoperative I-131 ablation. Median follow-up was 49 (range, 10-240) months. Outcome measures were recurrence rate, disease-free survival, and mean time to recurrence., Results: Ninety-seven patients had proven lymph node metastases. Recurrence rate was significantly higher in patients with positive lymph nodes in the lateral compartment vs. patients with lymph node metastasis in the central compartment (60 vs. 30%, p = 0.007). Disease-free survival and mean time to recurrence also were significantly shorter (30 vs. 52 months, p = 0.035 and 7 vs. 44 months, p = 0.004, respectively). The number of lymph nodes and extranodal growth were not significantly associated with the outcome measures used., Conclusions: The location of positive lymph nodes was significantly correlated with the risk of recurrence and a shorter DFS. Hence, the TNM criteria are useful in subdividing patients based on risk of recurrence and DFS.