Non-motor outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts

Background

Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in Parkinson's disease (PD). Few studies have investigated the influence of the location of neurostimulation on NMS.

Oxidative burden and mitochondrial dysfunction in a mouse model of Rett syndrome

Rett syndrome is an X chromosome-linked neurodevelopmental disorder associated with cognitive impairment, motor dysfunction and breathing irregularities causing intermittent hypoxia. Evidence for impaired mitochondrial function is also accumulating. A subunit of complex III is among the potentially dys-regulated genes, the inner mitochondrial membrane is leaking protons, brain ATP levels seem reduced, and Rett patient blood samples confirm increased oxidative damage. We therefore screened for mitochondrial dysfunction and impaired redox balance. In hippocampal slices of a Rett mouse model (Mecp2(-/y)) we detected an increased FAD/NADH baseline-ratio indicating intensified oxidization. Cyanide-induced anoxia caused similar decreases in FAD/NADH ratio and mitochondrial membrane potential in both genotypes, but Mecp2(-/y) mitochondria seemed less polarized. Quantifying cytosolic redox balance with the genetically-encoded optical probe roGFP1 confirmed more oxidized baseline conditions, a more vulnerable redox-balance, and more intense responses of Mecp2(-/y) hippocampus to oxidative challenge and mitochondrial impairment. Trolox treatment improved the redox baseline of Mecp2(-/y) hippocampus and dampened its exaggerated responses to oxidative challenge. Microarray analysis of the hippocampal CA1 subfield did not detect alterations of key mitochondrial enzymes or scavenging systems. Yet, quantitative PCR confirmed a moderate upregulation of superoxide dismutase 1 in Mecp2(-/y) hippocampus, which might be a compensatory response to the increased oxidative burden. Since several receptors and ion-channels are redox-modulated, the mitochondrial and redox changes which already manifest in neonates could contribute to the hyperexcitability and diminished synaptic plasticity in MeCP2 deficiency. Therefore, targeting cellular redox balance might qualify as a potential pharmacotherapeutic approach to improve neuronal network function in Rett syndrome.     

Extended cortical activations during evaluating successive pain stimuli

Comparing pain is done in daily life and involves short-term memorizing and attention focusing. This event-related functional magnetic resonance imaging study investigated the short-term brain activations associated with the comparison of pain stimuli using a delayed discrimination paradigm. Fourteen healthy young volunteers compared two successive pain stimuli administered at a 10 s interval to the same location at the nasal mucosa. Fourteen age- and sex-matched subjects received similar pain stimuli without performing the comparison task. With the comparison task, the activations associated with the second pain stimulus were significantly greater than with the first stimulus in the anterior insular cortex and the primary somatosensory area. This was observed on the background of a generally increased stimulus-associated brain activation in the presence of the comparison task that included regions of the pain matrix (insular cortex, primary and secondary somatosensory area, midcingulate cortex, supplemental motor area) and regions associated with attention, decision making, working memory and body recognition (frontal and temporal gyri, inferior parietal lobule, precuneus, lingual cortices). This data provides a cerebral correlate for the role of pain as a biological alerting system that gains the subject''s attention and then dominates most other perceptions and activities involving pain-specific and non-pain-specific brain regions.     

Positive affect as a factor of resilience in the pain-negative affect relationship in patients with rheumatoid arthritis

OBJECTIVE: The purpose of this study is to examine positive affect (PA) as a factor of resilience in the relationships between pain and negative affect (NA) in a sample of patients with rheumatoid arthritis. METHODS: Forty-three patients (30 women; mean age, 57 years) were interviewed weekly by telephone for 8 weeks. Multilevel modeling was applied to study the within-week relationships among the variables. RESULTS: There was a Pain x PA interaction effect on NA (beta=-0.05, P<.01) indicating a weaker relationship between pain and NA in weeks with more PA. Pain (beta=0.37, P<.002), interpersonal stress (beta=2.42, P<.001), depression (beta=0.26, P<.01), average perceived stress (beta=10.80, P<.001), and also weekly PA (beta=-0.1, P<.01) had a main effect upon NA. CONCLUSION: Positive affect is most influential in reducing NA during weeks of higher pain and may be a factor of resilience, helping patients experiencing pain fluctuations as less distressful than at lower levels of PA.     

Neurohumoral response and clinical effectiveness of continuous aortic flow augmentation in patients with decompensated heart failure

The increasing number of patients with progressive or exacerbated heart failure that is refractory to medical treatment necessitates the development of innovative cardiac assist devices. The aim of this study was to investigate whether a new percutaneously inserted system, which allows continuous aortic flow augmentation (CAFA), could be shown to be clinically effective with neurohormonal benefit in patients admitted with decompensated heart failure. Patients with exacerbations of chronic heart failure were recruited for the study. A percutaneous circulation assist device (Cancion system) promoting CAFA was implanted for up to 4 days in each patient. Clinical improvement was evaluated by measuring the clinical status according to the New York Heart Association (NYHA) classification and biochemical parameters including troponin and B-type natriuretic peptide (BNP) as markers of cardiac necrosis and cardiac overload; these parameters were measured before, during, and after CAFA treatment. The decrease in BNP was determined after implantation, reaching, on average, a maximum decrease of 57% at 72 h (P = 0.04). The neurohumoral response remained significant (P < 0.05) up to 120 h after implantation, with a decrease in BNP levels of 37%, on average, compared to baseline values. Troponin I did not show any significant change during mechanical assistance (P > 0.2). All patients had improved clinical status according to the NYHA classification, and the improvement lasted for more than 1 week. Percutaneous heart-assist devices promoting CAFA offer clinical improvement and a neurohumoral response, with a significant BNP reduction in severe exacerbation of chronic heart failure that is refractory to medical treatment.     

Volume loss in the deep gray matter and thalamic subnuclei: a longitudinal study on disability progression in multiple sclerosis

Journal of Neurology - Volume loss in the deep gray matter (DGM) has been reported in patients with multiple sclerosis (MS) already at early stages of the disease and is thought to progress...     

Short timescale modulation of cortical and cerebellar activity in the early phase of motor sequence learning: an fMRI study

Brain Imaging and Behavior - Motor learning is a multi-stage process, in which the involvement of different brain regions is related to the specific stage. We aimed at characterising short...     

Effects of media stories featuring coping with suicidal crises on psychiatric patients: Randomized controlled trial

BackgroundAccumulating evidence suggests beneficial effects of media stories featuring individuals mastering their suicidal crises, but effects have not been assessed for psychiatric patients.MethodsWe randomized n = 172 adult psychiatric patients (n = 172, 97.1% inpatients) to read an educative article featuring a person mastering a suicidal crisis (n = 92) or an unrelated article (n = 80) in a single-blind randomized controlled trial. Questionnaire data were collected before (T ₁) and after exposure (T ₂) as well as 1 week later (study end-point, T ₃). The primary outcome was suicidal ideation as assessed with the Reasons for Living Inventory; secondary outcomes were help-seeking intentions, mood, hopelessness, and stigmatization. Differences between patients with affective versus other diagnoses were explored based on interaction tests.ResultsWe found that patients with affective disorders (n = 99) experienced a small-sized reduction of suicidal ideation at 1-week follow up (mean difference to control group [MD] at T ₃ = −0.17 [95% CI −0.33, −0.03], d = −0.15), whereas patients with nonaffective diagnoses (n = 73) experienced a small-sized increase (T ₂: MD = 0.24 [95% CI 0.06, 0.42], d = 0.19). Intervention group participants further experienced a nonsustained increase of help-seeking intentions (T ₂: MD = 0.53 [95% CI 0.11, 0.95], d = 0.19) and a nonsustained deterioration of mood (T ₂: MD = −0.14 [95% CI −0.27, −0.02], d = −0.17).ConclusionsThis study suggests that patients with affective disorders appear to benefit from media materials featuring mastery of suicidal crises. More research is needed to better understand which patient groups are at possible risk of unintended effects.     

Tau kinase inhibitors protect hippocampal synapses despite of insoluble tau accumulation

A better understanding of the cellular and molecular pathomechanisms of Alzheimer's disease (AD) is a prerequisite for the development of efficient treatments. We have used a novel assay system based on virus-transduced organotypic hippocampal slice cultures that mimics important aspects of tau-driven AD pathology in a short time frame. Human tau P301L, when expressed in pyramidal neurons of hippocampal slice cultures, was increasingly phosphorylated at several disease-relevant epitopes, leading to progressive neuronal dystrophy and formation of RIPA-insoluble tau. AD-like tau hyperphosphorylation was reduced by the tau kinase inhibitors lithium and SRN-003-556, but RIPA-insoluble tau remained unaffected after treatment with any of these substances. Only SRN-003-556 was able to protect hippocampal neurons from synaptic damage that was presumably caused by a toxic soluble tau fraction. These data provide first mechanistic insights towards the functional benefits of SRN-003-556 that have been observed in vivo.