Neurophysiological signature(s) of visual hallucinations across neurological and perceptual:and non-invasive treatment with physical exercise

Hallucinations are common and stressful in many psychiatric, neurologic and perceptual disorders disturbing daily life, and increasing mortality, while current treatment of hallucinations is far from optimal. In current clinical practice, treatment with medication is selected in accordance with guidelines for the underlying diagnostic entity, not on the underlying mechanism of hallucinations per se. Understanding the pathophysiological mechanism of (subtypes of) hallucinations may provide new opportunities for treatment and enable rational choice of pharmacotherapy in a personalized manner increasing treatment efficacy and safety. In part I of this dissertation, we found common neurophysiological mechanism(s) underlying visual hallucinations (VH) across disorders. Although the hypothesis of altered attention in VH is not new and has been proposed in several individual disorders, its neurophysiological signature(s) have never been investigated and compared as such across a variety of disorders. This dissertation shows that VH across disorders are quite similar with regard to an underlying neurophysiological mechanism. This finding may aid the discovery of treatment options that could effectively alleviate these hallucinations across disorders, as it suggests that treatment effective for VH in one disorder may be beneficial for VH in another disorder too. In part II of this dissertation, we found evidence for the efficacy of physical exercise (PE) as an add-on treatment for clinical symptoms in schizophrenia spectrum disorder, but also for quality of life, depressive symptoms, and cognitive impairment in the chronic brain disorders Alzheimer’s disease, Huntington’s disease, Multiple Sclerosis, Parkinson’s disease, Schizophrenia, and Unipolar Depression

Author Correction:Functional connectome differences in individuals with hallucinations across the psychosis continuum (Scientific Reports, (2021), 11, 1, (1108), 10.1038/s41598-020-80657-8)

The Supplementary Information published with this Article contained an error, where an old version of Figure S5 was used. This error has now been corrected in the Supplementary Information file that accompanies the original Article. The corrected Supplementary Information file is also linked to this correction notices.</p

Understanding hallucinations in probable Alzheimer's disease:Very low prevalence rates in a tertiary memory clinic

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

Author Correction:Functional connectome differences in individuals with hallucinations across the psychosis continuum (Scientific Reports, (2021), 11, 1, (1108), 10.1038/s41598-020-80657-8)

The Supplementary Information published with this Article contained an error, where an old version of Figure S5 was used. This error has now been corrected in the Supplementary Information file that accompanies the original Article. The corrected Supplementary Information file is also linked to this correction notices

Functional connectome differences in individuals with hallucinations across the psychosis continuum

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.publishedVersio

Not the number but the location of lymph nodes matters for recurrence rate and disease-free survival in patients with differentiated thyroid cancer

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

The effect of mind-body and aerobic exercise on negative symptoms in schizophrenia:A meta-analysis

OBJECTIVE: This meta-analysis aims to evaluate the effects of different types of physical exercise (PE) on negative symptoms in schizophrenia patients. Mind-body exercise (MBE), aerobic exercise (AE) and resistance training (RT) will be investigated. METHOD: The Cochrane Library, Medline, Embase and PsycINFO were searched from their inception until April 26, 2018. Randomized controlled trials comparing PE with any control group in patients with schizophrenia were included when negative symptoms had been assessed. This meta-analysis was conducted according to the PRISMA guidelines. The methodological quality of the included studies was assessed with the Cochrane Risk of Bias assessment tool. Moderator, sensitivity, and meta regression analyses were conducted to explore causes of heterogeneity and impact of study quality. RESULTS: We included 22 studies (N = 1249). The overall methodological quality was poor. The meta-analysis (random effects model) showed a medium significant effect in favor of any PE intervention (Hedges' g = 0.434, 95% CI = 0.196-0.671) versus any control condition. MBE and AE respectively showed a medium significant effect (Hedges' g = 0.461) and a small significant effect (Hedges' g = 0.341) versus any control condition. The effect of RT could not be examined. The overall heterogeneity was high (I2 = 76%) and could not be reduced with moderator or sensitivity analyses. CONCLUSION: This meta-analysis demonstrated that PE could be a promising intervention in the treatment of negative symptoms. However, the quality of the included studies was low and heterogeneity was high, which makes it impossible to make a clear recommendation. Therefore, results should be interpreted with care

Using motivational techniques to reduce cardiometabolic risk factors in long term psychiatric inpatients: A naturalistic interventional study

Background People with severe mental illness have markedly reduced life expectancy; cardiometabolic disease is a major cause. Psychiatric hospital inpatients have elevated levels of cardiometabolic risk factors and are to a high degree dependent of the routines and facilities of the institutions. Studies of lifestyle interventions to reduce cardiometabolic risk in psychiatric inpatients are few. The current study aimed at assessing the feasibility and effects of a lifestyle intervention including Motivational Interviewing (MI) on physical activity levels, cardiometabolic risk status and mental health status in psychotic disorder inpatients. Methods Prospective naturalistic intervention study of 83 patients at long term inpatient psychosis treatment wards in South-Eastern Norway. Patients were assessed 3–6 months prior to, at start and 6 months after a life-style intervention program including training of staff in MI, simple changes in routines and improvements of facilities for physical exercise. Assessments were done by clinical staff and included level of physical activity, motivation, life satisfaction, symptom levels (MADRS, AES-C, PANSS, and GAF) as well as anthropometric and biochemical markers of cardiometabolic risk. A mixed model was applied to analyze change over time. Results A total of 88% of patients received MI interventions, with a mean of 2.5 MI interventions per week per patient. The physical activity level was not increased, but activity level was positively associated with motivation and negatively associated with positive symptoms. Triglyceride levels and number of smokers were significantly reduced and a significant decrease in symptom levels was observed. Conclusions The current results suggest that a simple, low cost life-style intervention program focusing on motivational change is feasible and may reduce symptoms and improve lifestyle habits in psychosis patients in long term treatment facilities. Similar programs may easily be implemented in other psychiatric hospitals.submittedVersio

What Electrophysiology Tells Us About Alzheimer’s Disease::A Window into the Synchronization and Connectivity of Brain Neurons

Electrophysiology provides a real-time readout of neural functions and network capability in different brain states, on temporal (fractions of milliseconds) and spatial (micro, meso, and macro) scales unmet by other methodologies. However, current international guidelines do not endorse the use of electroencephalographic (EEG)/magnetoencephalographic (MEG) biomarkers in clinical trials performed in patients with Alzheimer’s disease (AD), despite a surge in recent validated evidence. This Position Paper of the ISTAART Electrophysiology Professional Interest Area endorses consolidated and translational electrophysiological techniques applied to both experimental animal models of AD and patients, to probe the effects of AD neuropathology (i.e., brain amyloidosis, tauopathy, and neurodegeneration) on neurophysiological mechanisms underpinning neural excitation/inhibition and neurotransmission as well as brain network dynamics, synchronization, and functional connectivity reflecting thalamocortical and cortico-cortical residual capacity. Converging evidence shows relationships between abnormalities in EEG/MEG markers and cognitive deficits in groups of AD patients at different disease stages. The supporting evidence for the application of electrophysiology in AD clinical research as well as drug discovery pathways warrants an international initiative to include the use of EEG/MEG biomarkers in the main multicentric projects planned in AD patients, to produce conclusive findings challenging the present regulatory requirements and guidelines for AD studies