Human Fronto-Tectal and Fronto-Striatal-Tectal Pathways Activate Differently During Anti-Saccades

Almost all cortical areas in the vertebrate brain take part in recurrent connections through the subcortical basal ganglia (BG) nuclei, through parallel inhibitory and excitatory loops. It has been suggested that these circuits can modulate our reactions to external events such that appropriate reactions are chosen from many available options, thereby imposing volitional control over behavior. The saccade system is an excellent model system to study cortico-BG interactions. In this study two possible pathways were investigated that might regulate automaticity of eye movements in the human brain; the cortico-tectal pathway, running directly between the frontal eye fields (FEF) and superior colliculus (SC) and the cortico-striatal pathway from the FEF to the SC involving the caudate nucleus (CN) in the BG. In an event-related functional magnetic resonance imaging (fMRI) paradigm participants made pro- and anti-saccades. A diffusion tensor imaging (DTI) scan was made for reconstruction of white matter tracts between the FEF, CN and SC. DTI fiber tracts were used to divide both the left and right FEF into two sub-areas, projecting to either ipsilateral SC or CN. For each of these FEF zones an event-related fMRI timecourse was extracted. In general activity in the FEF was larger for anti-saccades. This increase in activity was lateralized with respect to anti-saccade direction in FEF zones connected to the SC but not for zones only connected to the CN. These findings suggest that activity along the contralateral FEF–SC projection is responsible for directly generating anti-saccades, whereas the pathway through the BG might merely have a gating function withholding or allowing a pro-saccade

Introducing the DizzyQuest: an app-based diary for vestibular disorders

BACKGROUND Most questionnaires currently used for assessing symptomatology of vestibular disorders are retrospective, inducing recall bias and lowering ecological validity. An app-based diary, administered multiple times in daily life, could increase the accuracy and ecological validity of symptom measurement. The objective of this study was to introduce a new experience sampling method (ESM) based vestibular diary app (DizzyQuest), evaluate response rates, and to provide examples of DizzyQuest outcome measures which can be used in future research. METHODS Sixty-three patients diagnosed with a vestibular disorder were included. The DizzyQuest consisted of four questionnaires. The morning- and evening-questionnaires were administered once each day, the within-day-questionnaire 10 times a day using a semi-random time schedule, and the attack questionnaire could be completed after the occurrence of a vertigo or dizziness attack. Data were collected for 4~weeks. Response rates and loss-to-follow-up were determined. Reported symptoms in the within-day-questionnaire were compared within and between patients and subgroups of patients with different vestibular disorders. RESULTS Fifty-one patients completed the study period. Average response rates were significantly higher than the desired response rate of \textgreater 50% (p \textless 0.001). The attack-questionnaire was used 159 times. A variety of neuro-otological symptoms and different disease profiles were demonstrated between patients and subgroups of patients with different vestibular disorders. CONCLUSION The DizzyQuest is able to capture vestibular symptoms within their psychosocial context in daily life, with little recall bias and high ecological validity. The DizzyQuest reached the desired response rates and showed different disease profiles between subgroups of patients with different vestibular disorders. This is the first time ESM was used to assess daily symptoms and quality of life in vestibular disorders, showing that it might be a useful tool in this population

Exercise-induced modulation of cardiac lipid content in healthy lean young men

Cardiac lipid accumulation is associated with decreased cardiac function and energy status (PCr/ATP). It has been suggested that elevated plasma fatty acid (FA) concentrations are responsible for the cardiac lipid accumulation. Therefore, the aim of the present study was to investigate if elevating plasma FA concentrations by exercise results in an increased cardiac lipid content, and if this influences cardiac function and energy status. Eleven male subjects (age 25.4 ± 1.1 years, BMI 23.6 ± 0.8 kg/m2) performed a 2-h cycling protocol, once while staying fasted and once while ingesting glucose, to create a state of high versus low plasma FA concentrations, respectively. Cardiac lipid content was measured by proton magnetic resonance spectroscopy (1H-MRS) at baseline, directly after exercise and again 4 h post-exercise, together with systolic function (by multi-slice cine-MRI) and cardiac energy status (by 31P-MRS). Plasma FA concentrations were increased threefold during exercise and ninefold during recovery in the fasted state compared with the glucose-fed state (p < 0.01). Cardiac lipid content was elevated at the end of the fasted test day (from 0.26 ± 0.04 to 0.44 ± 0.04%, p = 0.003), while it did not change with glucose supplementation (from 0.32 ± 0.03 to 0.26 ± 0.05%, p = 0.272). Furthermore, PCr/ATP was decreased by 32% in the high plasma FA state compared with the low FA state (n = 6, p = 0.014). However, in the high FA state, the ejection fraction 4 h post-exercise was higher compared with the low FA state (63 ± 2 vs. 59 ± 2%, p = 0.018). Elevated plasma FA concentrations, induced by exercise in the fasted state, lead to increased cardiac lipid content, but do not acutely hamper systolic function. Although the lower cardiac energy status is in line with a lipotoxic action of cardiac lipid content, a causal relationship cannot be proven

Celio (\u2705), Orkand (\u2707) Named Up and Coming Leaders

BackgroundAlthough auditory verbal hallucinations (AVH) are a core symptom of schizophrenia, they also occur in non-psychotic individuals, in the absence of other psychotic, affective, cognitive and negative symptoms. AVH have been hypothesized to result from deviant integration of inferior frontal, parahippocampal and superior temporal brain areas. However, a direct link between dysfunctional connectivity and AVH has not yet been established. To determine whether hallucinations are indeed related to aberrant connectivity, AVH should be studied in isolation, for example in non-psychotic individuals with AVH.MethodResting-state connectivity was investigated in 25 non-psychotic subjects with AVH and 25 matched control subjects using seed regression analysis with the (1) left and (2) right inferior frontal, (3) left and (4) right superior temporal and (5) left parahippocampal areas as the seed regions. To correct for cardiorespiratory (CR) pulsatility rhythms in the functional magnetic resonance imaging (fMRI) data, heartbeat and respiration were monitored during scanning and the fMRI data were corrected for these rhythms using the image-based method for retrospective correction of physiological motion effects RETROICOR.ResultsIn comparison with the control group, non-psychotic individuals with AVH showed increased connectivity between the left and the right superior temporal regions and also between the left parahippocampal region and the left inferior frontal gyrus. Moreover, this group did not show a negative correlation between the left superior temporal region and the right inferior frontal region, as was observed in the healthy control group.ConclusionsAberrant connectivity of frontal, parahippocampal and superior temporal brain areas can be specifically related to the predisposition to hallucinate in the auditory domain.</jats:sec

Coloring local feature extraction

International audienceAlthough color is commonly experienced as an indispensable quality in describing the world around us, state-of-the art local feature-based representations are mostly based on shape description, and ignore color information. The description of color is hampered by the large amount of variations which causes the measured color values to vary significantly. In this paper we aim to extend the description of local features with color information. To accomplish a wide applicability of the color descriptor, it should be robust to : 1. photometric changes commonly encountered in the real world, 2. varying image quality, from high quality images to snap-shot photo quality and compressed internet images. Based on these requirements we derive a set of color descriptors. The set of proposed descriptors are compared by extensive testing on multiple applications areas, namely, matching, retrieval and classification, and on a wide variety of image qualities. The results show that color descriptors remain reliable under photometric and geometrical changes, and with decreasing image quality. For all experiments a combination of color and shape outperforms a pure shape-based approach

Multivariate genome-wide analyses of the well-being spectrum

We introduce two novel methods for multivariate genome-wide-association meta-analysis (GWAMA) of related traits that correct for sample overlap. A broad range of simulation scenarios supports the added value of our multivariate methods relative to univariate GWAMA. We applied the novel methods to life satisfaction, positive affect, neuroticism, and depressive symptoms, collectively referred to as the well-being spectrum (Nobs = 2,370,390), and found 304 significant independent signals. Our multivariate approaches resulted in a 26% increase in the number of independent signals relative to the four univariate GWAMAs and in an ~57% increase in the predictive power of polygenic risk scores. Supporting transcriptome- and methylome-wide analyses (TWAS and MWAS, respectively) uncovered an additional 17 and 75 independent loci, respectively. Bioinformatic analyses, based on gene expression in brain tissues and cells, showed that genes differentially expressed in the subiculum and GABAergic interneurons are enriched in their effect on the well-being spectrum

High cellular monocyte activation in people living with human immunodeficiency virus on combination antiretroviral therapy and lifestyle-matched controls is associated with greater inflammation in cerebrospinal fluid

Background. Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). Methods. A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD). Results. People living with HIV, HIV-negative individuals, and BBD had comparable percentages of classical, intermediate, and nonclassical monocytes. Expression of CD163, CD32, CD64, HLA-DR, CD38, CD40, CD86, CD91, CD11c, and CX3CR1 on monocytes did not differ between PLHIV and HIV-negative individuals, but it differed significantly from BBD. Principal component analysis revealed that 57.5% of PLHIV and 62.5% of HIV-negative individuals had a high monocyte activation profile compared with 2.9% of BBD. Cellular monocyte activation in the COBRA cohort was strongly associated with soluble markers of monocyte activation and inflammation in the CSF. Conclusions. People living with HIV and HIV-negative COBRA participants had high levels of cellular monocyte activation compared with age-matched BBD. High monocyte activation was predictive for inflammation in the CSF

Testing effectiveness of the revised Cape Town modified early warning and SBAR systems: a pilot pragmatic parallel group randomised controlled trial

Abstract Background Nurses’ recognition of clinical deterioration is crucial for patient survival. Evidence for the effectiveness of modified early warning scores (MEWS) is derived from large observation studies in developed countries. Methods We tested the effectiveness of the paper-based Cape Town (CT) MEWS vital signs observation chart and situation-background-assessment-recommendation (SBAR) communication guide. Outcomes were: proportion of appropriate responses to deterioration, differences in recording of clinical parameters and serious adverse events (SAEs) in intervention and control trial arms. Public teaching hospitals for adult patients in Cape Town were randomised to implementation of the CT MEWS/SBAR guide or usual care (observation chart without track-and-trigger information) for 31 days on general medical and surgical wards. Nurses in intervention wards received training, as they had no prior knowledge of early warning systems. Identification and reporting of patient deterioration in intervention and control wards were compared. In the intervention arm, 24 day-shift and 23 night-shift nurses received training. Clinical records were reviewed retrospectively at trial end. Only records of patients who had given signed consent were reviewed. Results We recruited two of six CT general hospitals. We consented 363 patients and analysed 292 (80.4%) patient records (n = 150, 51.4% intervention, n = 142, 48.6% control arm). Assistance was summoned for fewer patients with abnormal vital signs in the intervention arm (2/45, 4.4% versus (vs) 11/81, 13.6%, OR 0.29 (0.06–1.39)), particularly low systolic blood pressure. There was a significant difference in recording between trial arms for parameters listed on the MEWS chart but omitted from the standard observations chart: oxygen saturation, level of consciousness, pallor/cyanosis, pain, sweating, wound oozing, pedal pulses, glucose concentration, haemoglobin concentration, and “looks unwell”. SBAR was used twice. There was no statistically significant difference in SAEs (5/150, 3.3% vs 3/143, 2.1% P = 0.72, OR 1.61 (0.38–6.86)). Conclusions The revised CT MEWS observations chart improved recording of certain parameters, but did not improve nurses’ ability to identify early signs of clinical deterioration and to summon assistance. Recruitment of only two hospitals and exclusion of patients too ill to consent limits generalisation of results. Further work is needed on educational preparation for the CT MEWS/SBAR and its impact on nurses’ reporting behaviour. Trial registration Pan African Clinical Trials Registry, PACTR201406000838118. Registered on 2 June 2014, www.pactr.org

HGF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice

The MET protooncogene, c-MET, encodes a cell surface tyrosine kinase receptor. The ligand for c-MET is hepatocyte growth factor (HGF), also known as scatter factor (SF), which is known to affect proliferation and motility of primarily epithelial cells. Recently, HGF/SF was also shown to affect haemopoiesis. Studies with epithelial and transfected NIH3T3 cells indicated that the HGF/SF–c-MET interaction promotes invasion in vitro and in vivo. We previously demonstrated that HGF/SF induces adhesion of c-MET-positive B-lymphoma cells to extracellular matrix molecules, and promoted migration and invasion in in vitro assays. Here, the effect of HGF/SF on tumorigenicity of c-MET-positive and c-MET-negative human B-lymphoma cell lines was studied in C.B-17 scid/scid (severe combined immune deficient) mice. Intravenously (i.v.) injected c-MET-positive (BJAB) as well as c-MET-negative (Daudi and Ramos cells) B-lymphoma cells formed tumours in SCID mice. The B-lymphoma cells invaded different organs, such as liver, kidney, lymph nodes, lung, gonads and the central nervous system. We assessed the effect of human HGF/SF on the dissemination of the B-lymphoma cells and found that administration of 5 μg HGF/SF to mice, injected (i.v.) with c-MET-positive lymphoma cells, significantly (P = 0.018) increased the number of metastases in lung, liver and lymph nodes. In addition, HGF/SF did not significantly influence dissemination of c-MET-negative lymphoma cells (P = 0.350 with Daudi cells and P = 0.353 with Ramos cells). Thus the effect of administration of HGF/SF on invasion of lymphoma cells is not an indirect one, e.g. via an effect on endothelial cells. Finally, we investigated the effect of HGF/SF on dissemination of c-MET-transduced Ramos cells. In response to HGF/SF, c-MET-transduced Ramos cells showed an increased migration through Matrigel in Boyden chambers compared to wild-type and control-transduced Ramos cells. The dissemination pattern of c-MET-transduced cells did not differ from control cells in in vivo experiments using SCID mice. Also no effect of HGF/SF administration could be documented, in contrast to the in vitro experiments. From our experiments can be concluded that the HGF/SF–c-MET interaction only plays a minor role in the dissemination of human B-lymphoma cells. © 1999 Cancer Research Campaig

A Functional and Structural Investigation of the Human Fronto-Basal Volitional Saccade Network

Almost all cortical areas are connected to the subcortical basal ganglia (BG) through parallel recurrent inhibitory and excitatory loops, exerting volitional control over automatic behavior. As this model is largely based on non-human primate research, we used high resolution functional MRI and diffusion tensor imaging (DTI) to investigate the functional and structural organization of the human (pre)frontal cortico-basal network controlling eye movements. Participants performed saccades in darkness, pro- and antisaccades and observed stimuli during fixation. We observed several bilateral functional subdivisions along the precentral sulcus around the human frontal eye fields (FEF): a medial and lateral zone activating for saccades in darkness, a more fronto-medial zone preferentially active for ipsilateral antisaccades, and a large anterior strip along the precentral sulcus activating for visual stimulus presentation during fixation. The supplementary eye fields (SEF) were identified along the medial wall containing all aforementioned functions. In the striatum, the BG area receiving almost all cortical input, all saccade related activation was observed in the putamen, previously considered a skeletomotor striatal subdivision. Activation elicited by the cue instructing pro or antisaccade trials was clearest in the medial FEF and right putamen. DTI fiber tracking revealed that the subdivisions of the human FEF complex are mainly connected to the putamen, in agreement with the fMRI findings. The present findings demonstrate that the human FEF has functional subdivisions somewhat comparable to non-human primates. However, the connections to and activation in the human striatum preferentially involve the putamen, not the caudate nucleus as is reported for monkeys. This could imply that fronto-striatal projections for the oculomotor system are fundamentally different between humans and monkeys. Alternatively, there could be a bias in published reports of monkey studies favoring the caudate nucleus over the putamen in the search for oculomotor functions