Visual Hallucinations in Eye Disease and Lewy Body Disease

Objective: Visual hallucinations (VH) most commonly occur in eye disease (ED), Parkinson’s disease (PD), and Lewy body dementia (LBD). The phenomenology of VH is likely to carry important information about the brain areas within the visual system generating them. Methods: Data from five controlled cross-sectional VH studies (164 controls, 135 ED, 156 PD, 79 (PDD 48 + DLB 31) LBD) were combined and analysed. The prevalence, phenomenology, frequency, duration, and contents of VH were compared across diseases and gender. Results: Simple VH were most common in ED patients (ED 65% vs. LBD 22% vs. PD 9%, Chi-square [χ2] test: χ2=31.43, df=2, p<0.001), whilst complex VH were more common in LBD (LBD 76% vs. ED 38%, vs PD 28%, Chi-square test: χ2=96.80, df=2, p<0.001). The phenomenology of complex VH was different across diseases and gender. ED patients reported more “flowers” (ED 21% vs. LBD 6% vs. PD 0%, Chi-square test: χ2=10.04, df=2, p=0.005) and “body parts” (ED 40% vs. LBD 17% vs. PD 13%, Chi-square test: χ2=11.14, df=2, p=0.004); in contrast LBD patients reported “people” (LBD 85% vs. ED 67% vs. PD 63%, Chi-square test: χ2=6.20, df=2, p=0.045) and “animals/insects” (LBD 50% vs. PD 42% vs. ED 21%, Chi-square test: χ2=9.76, df=2, p=0.008). Males reported more “machines” (13 % vs. 2%, Chi-square test: χ2=6.94, df=1, p=0.008), whilst females reported more “family members/children” (48% vs. 29%, Chi-square test: χ2=5.10, df=1, p=0.024). Conclusions: The phenomenology of VH is likely related to disease specific dysfunctions within the visual system and to past, personal experiences.

Effects of Anxiety on Anticipation and Visual Search in Dynamic, Time-Constrained Situations

We tested the predictions of Attentional Control Theory (ACT) by examining how anxiety affects visual search strategies, performance efficiency, and performance effectiveness using a dynamic, temporal-constrained anticipation task. Higher and lower skilled players viewed soccer situations under 2 task constraints (near vs. far situation) and were tested under high (HA) and low (LA) anxiety conditions. Response accuracy (effectiveness) and response time, perceived mental effort, and eye-movements (all efficiency) were recorded. A significant increase in anxiety was evidenced by higher state anxiety ratings on the MRF-L scale. Increased anxiety led to decreased performance efficiency because response times and mental effort increased for both skill groups whereas response accuracy did not differ. Anxiety influenced search strategies, with higher skilled players showing a decrease in number of fixation locations for far situations under HA compared with LA condition when compared with lower skilled players. Findings provide support for ACT with anxiety impairing processing efficiency and, potentially, top-down attentional control across different task constraints.

Assessment of the role of LASER-Doppler in the treatment of port-wine stains in infants

BACKGROUND Port-wine stains (PWS) are malformations of capillaries in 0.3% of newborn children. The treatment of choice is by pulsed dye LASER (PDL), and requires several sessions. The efficacy of this treatment is at present evaluated on the basis of clinical inspection and of digital photographs taken throughout the treatment. LASER-Doppler imaging (LDI) is a noninvasive method of imaging the perfusion of the tissues by the microcirculatory system (capillaries). The aim of this paper is to demonstrate that LDI allows a quantitative, numerical evaluation of the efficacy of the PDL treatment of PWS. METHOD The PDL sessions were organized according to the usual scheme, every other month, from September 1, 2012, to September 30, 2013. LDI imaging was performed at the start and at the conclusion of the PDL treatment, and simultaneously on healthy skin in order to obtain reference values. The results evidenced by LDI were analyzed according to the "Wilcoxon signed-rank" test before and after each session, and in the intervals between the three PDL treatment sessions. RESULTS Our prospective study is based on 20 new children. On average, the vascularization of the PWS was reduced by 56% after three laser sessions. Compared with healthy skin, initial vascularization of PWS was 62% higher than that of healthy skin at the start of treatment, and 6% higher after three sessions. During the 2 months between two sessions, vascularization of the capillary network increased by 27%. CONCLUSION This study shows that LDI can demonstrate and measure the efficacy of PDL treatment of PWS in children. The figures obtained when measuring the results by LDI corroborate the clinical assessments and may allow us to refine, and perhaps even modify, our present use of PDL and thus improve the efficacy of the treatment.

Theta burst stimulation improves overt visual search in spatial neglect independently of attentional load

Visual neglect is considerably exacerbated by increases in visual attentional load. These detrimental effects of attentional load are hypothesised to be dependent on an interplay between dysfunctional inter-hemispheric inhibitory dynamics and load-related modulation of activity in cortical areas such as the posterior parietal cortex (PPC). Continuous Theta Burst Stimulation (cTBS) over the contralesional PPC reduces neglect severity. It is unknown, however, whether such positive effects also operate in the presence of the detrimental effects of heightened attentional load. Here, we examined the effects of cTBS on neglect severity in overt visual search (i.e., with eye movements), as a function of high and low visual attentional load conditions. Performance was assessed on the basis of target detection rates and eye movements, in a computerised visual search task and in two paper-pencil tasks. cTBS significantly ameliorated target detection performance, independently of attentional load. These ameliorative effects were significantly larger in the high than the low load condition, thereby equating target detection across both conditions. Eye movement analyses revealed that the improvements were mediated by a redeployment of visual fixations to the contralesional visual field. These findings represent a substantive advance, because cTBS led to an unprecedented amelioration of overt search efficiency that was independent of visual attentional load.

False normal Lung Clearance Index in infants with cystic fibrosis due to software algorithms.

BACKGROUND Lung clearance index (LCI), a marker of ventilation inhomogeneity, is elevated early in children with cystic fibrosis (CF). However, in infants with CF, LCI values are found to be normal, although structural lung abnormalities are often detectable. We hypothesized that this discrepancy is due to inadequate algorithms of the available software package. AIM Our aim was to challenge the validity of these software algorithms. METHODS We compared multiple breath washout (MBW) results of current software algorithms (automatic modus) to refined algorithms (manual modus) in 17 asymptomatic infants with CF, and 24 matched healthy term-born infants. The main difference between these two analysis methods lies in the calculation of the molar mass differences that the system uses to define the completion of the measurement. RESULTS In infants with CF the refined manual modus revealed clearly elevated LCI above 9 in 8 out of 35 measurements (23%), all showing LCI values below 8.3 using the automatic modus (paired t-test comparing the means, P < 0.001). Healthy infants showed normal LCI values using both analysis methods (n = 47, paired t-test, P = 0.79). The most relevant reason for false normal LCI values in infants with CF using the automatic modus was the incorrect recognition of the end-of-test too early during the washout. CONCLUSION We recommend the use of the manual modus for the analysis of MBW outcomes in infants in order to obtain more accurate results. This will allow appropriate use of infant lung function results for clinical and scientific purposes.

Accuracy of tidal breathing measurement of FloRight compared to an ultrasonic flowmeter in infants.

INTRODUCTION Monitoring breathing pattern is especially relevant in infants with lung disease. Recently, a vest-based inductive plethysmograph system (FloRight®) has been developed for tidal breathing measurement in infants. We investigated the accuracy of tidal breathing flow volume loop (TBFVL) measurements in healthy term-born infants and infants with lung disease by the vest-based system in comparison to an ultrasonic flowmeter (USFM) with a face mask. We also investigated whether the system discriminates between healthy infants and those with lung disease. METHODS Floright® measures changes in thoracoabdominal volume during tidal breathing through magnetic field changes generated by current-carrying conductor coils in an elastic vest. Simultaneous TBFVL measurements by the vest-based system and the USFM were performed at 44 weeks corrected postmenstrual age during quiet unsedated sleep. TBFVL parameters derived by both techniques and within both groups were compared. RESULTS We included 19 healthy infants and 18 infants with lung disease. Tidal volume per body weight derived by the vest-based system was significantly lower with a mean difference (95% CI) of -1.33 ml/kg (-1.73; -0.92), P < 0.001. Respiratory rate and ratio of time to peak tidal expiratory flow over total expiratory time (tPTEF/tE) did not differ between the two techniques. Both systems were able to discriminate between healthy infants and those with lung disease using tPTEF/tE. CONCLUSION FloRight® accurately measures time indices and may discriminate between healthy infants and those with lung disease, but demonstrates differences in tidal volume measurements. It may be better suited to monitor breathing pattern than for TBFVL measurements.

The influence of naturalistic, directionally non-specific motion on the spatial deployment of visual attention in right-hemispheric stroke

An impairment of the spatial deployment of visual attention during exploration of static (i.e., motionless) stimuli is a common finding after an acute, right-hemispheric stroke. However, less is known about how these deficits: a) are modulated through naturalistic motion (i.e., without directional, specific spatial features); and, b) evolve in the subacute/chronic post-stroke phase. In the present study, we investigated free visual exploration in three patient groups with subacute/chronic right-hemispheric stroke and in healthy subjects. The first group included patients with left visual neglect and a left visual field defect (VFD), the second patients with a left VFD but no neglect, and the third patients without neglect or VFD. Eye movements were measured in all participants while they freely explored a traffic scene without (static condition) and with (dynamic condition) naturalistic motion, i.e., cars moving from the right or left. In the static condition, all patient groups showed similar deployment of visual exploration (i.e., as measured by the cumulative fixation duration) as compared to healthy subjects, suggesting that recovery processes took place, with normal spatial allocation of attention. However, the more demanding dynamic condition with moving cars elicited different re-distribution patterns of visual attention, quite similar to those typically observed in acute stroke. Neglect patients with VFD showed a significant decrease of visual exploration in the contralesional space, whereas patients with VFD but no neglect showed a significant increase of visual exploration in the contralesional space. No differences, as compared to healthy subjects, were found in patients without neglect or VFD. These results suggest that naturalistic motion, without directional, specific spatial features, may critically influence the spatial distribution of visual attention in subacute/chronic stroke patients.

Rhinovirus Infections and Associated Respiratory Morbidity in Infants: A Prospective Cohort Study.

BACKGROUND Risk factors promoting rhinovirus (RV) infections are inadequately described in healthy populations, especially infants. OBJECTIVES To determine the frequency of symptomatic and asymptomatic RV infections and identify possible risk factors from host and environment among otherwise healthy infants. METHODS In a prospective birth cohort, respiratory health was assessed in 41 term-born infants by weekly telephone interviews during the first year of life, and weekly nasal swabs were collected to determine RV prevalence. In a multilevel logistic regression model, associations between prevalence and respiratory symptoms during RV infections and host/environmental factors were determined. RESULTS 27% of nasal swabs in 41 infants tested positive for RVs. Risk factors for RV prevalence were autumn months (OR=1.71, p=0.01, 95% CI 1.13-2.61), outdoor temperatures between 5-10 °C (OR=2.33, p=0.001, 95% CI 1.41-3.86), older siblings (OR=2.60, p=0.001, 95% CI 1.50-4.51) and childcare attendance (OR=1.53, p=0.07, 95% CI 0.96-2.44). 51% of RV-positive samples were asymptomatic. Respiratory symptoms during RV infections were less likely during the first three months of life (OR=0.34, p=0.003, 95% CI 0.17-0.69) and in infants with atopic mothers (OR=0.44, p=0.008, 95% CI 0.24-0.80). Increased tidal volume (OR=1.67, p=0.03, 95% CI 1.04-2.68) and outdoor temperatures between 2-5 °C (OR=2.79, p=0.02, 95% CI 1.17-6.61) were associated with more symptoms. CONCLUSIONS RVs are highly prevalent during the first year of life, and most infections are asymptomatic. Frequency of RV infections is associated with environmental factors, while respiratory symptoms during RV infections are linked to host determinants like infant age, maternal atopy, or premorbid lung function.

The nasal microbiota in infants with cystic fibrosis in the first year of life: a prospective cohort study.

BACKGROUND Respiratory tract infections and subsequent airway inflammation occur early in the life of infants with cystic fibrosis. However, detailed information about the microbial composition of the respiratory tract in infants with this disorder is scarce. We aimed to undertake longitudinal in-depth characterisation of the upper respiratory tract microbiota in infants with cystic fibrosis during the first year of life. METHODS We did this prospective cohort study at seven cystic fibrosis centres in Switzerland. Between Feb 1, 2011, and May 31, 2014, we enrolled 30 infants with a diagnosis of cystic fibrosis. Microbiota characterisation was done with 16S rRNA gene pyrosequencing and oligotyping of nasal swabs collected every 2 weeks from the infants with cystic fibrosis. We compared these data with data for an age-matched cohort of 47 healthy infants. We additionally investigated the effect of antibiotic treatment on the microbiota of infants with cystic fibrosis. Statistical methods included regression analyses with a multivariable multilevel linear model with random effects to correct for clustering on the individual level. FINDINGS We analysed 461 nasal swabs taken from the infants with cystic fibrosis; the cohort of healthy infants comprised 872 samples. The microbiota of infants with cystic fibrosis differed compositionally from that of healthy infants (p=0·001). This difference was also found in exclusively antibiotic-naive samples (p=0·001). The disordering was mainly, but not solely, due to an overall increase in the mean relative abundance of Staphylococcaceae in infants with cystic fibrosis compared with healthy infants (multivariable linear regression model stratified by age and adjusted for season; second month: coefficient 16·2 [95% CI 0·6-31·9]; p=0·04; third month: 17·9 [3·3-32·5]; p=0·02; fourth month: 21·1 [7·8-34·3]; p=0·002). Oligotyping analysis enabled differentiation between Staphylococcus aureus and coagulase-negative Staphylococci. Whereas the analysis showed a decrease in S aureus at and after antibiotic treatment, coagulase-negative Staphylococci increased. INTERPRETATION Our study describes compositional differences in the microbiota of infants with cystic fibrosis compared with healthy controls, and disordering of the microbiota on antibiotic administration. Besides S aureus, coagulase-negative Staphylococci also contributed to the disordering identified in these infants. These findings are clinically important in view of the crucial role that bacterial pathogens have in the disease progression of cystic fibrosis in early life. Our findings could be used to inform future studies of the effect of antibiotic treatment on the microbiota in infants with cystic fibrosis, and could assist in the prevention of early disease progression in infants with this disorder. FUNDING Swiss National Science Foundation, Fondation Botnar, the Swiss Society for Cystic Fibrosis, and the Swiss Lung Association Bern.

Interhemispheric connections shape subjective experience of bistable motion

The right and left visual hemifields are represented in different cerebral hemispheres and are bound together by connections through the corpus callosum. Much has been learned on the functions of these connections from split-brain patients [1-4], but little is known about their contribution to conscious visual perception in healthy humans. We used diffusion tensor imaging and functional magnetic resonance imaging to investigate which callosal connections contribute to the subjective experience of a visual motion stimulus that requires interhemispheric integration. The "motion quartet" is an ambiguous version of apparent motion that leads to perceptions of either horizontal or vertical motion [5]. Interestingly, observers are more likely to perceive vertical than horizontal motion when the stimulus is presented centrally in the visual field [6]. This asymmetry has been attributed to the fact that, with central fixation, perception of horizontal motion requires integration across hemispheres whereas perception of vertical motion requires only intrahemispheric processing [7]. We are able to show that the microstructure of individually tracked callosal segments connecting motion-sensitive areas of the human MT/V5 complex (hMT/V5+; [8]) can predict the conscious perception of observers. Neither connections between primary visual cortex (V1) nor other surrounding callosal regions exhibit a similar relationship.

Auditory motion direction encoding in auditory cortex and high-level visual cortex

The aim of this functional magnetic resonance imaging (fMRI) study was to identify human brain areas that are sensitive to the direction of auditory motion. Such directional sensitivity was assessed in a hypothesis-free manner by analyzing fMRI response patterns across the entire brain volume using a spherical-searchlight approach. In addition, we assessed directional sensitivity in three predefined brain areas that have been associated with auditory motion perception in previous neuroimaging studies. These were the primary auditory cortex, the planum temporale and the visual motion complex (hMT/V5+). Our whole-brain analysis revealed that the direction of sound-source movement could be decoded from fMRI response patterns in the right auditory cortex and in a high-level visual area located in the right lateral occipital cortex. Our region-of-interest-based analysis showed that the decoding of the direction of auditory motion was most reliable with activation patterns of the left and right planum temporale. Auditory motion direction could not be decoded from activation patterns in hMT/V5+. These findings provide further evidence for the planum temporale playing a central role in supporting auditory motion perception. In addition, our findings suggest a cross-modal transfer of directional information to high-level visual cortex in healthy humans.

Respiratory muscle activity related to flow and lung volume in preterm infants compared with term infants

Infants with chronic lung disease (CLD) have a capacity to maintain functional lung volume despite alterations to their lung mechanics. We hypothesize that they achieve this by altering breathing patterns and dynamic elevation of lung volume, leading to differences in the relationship between respiratory muscle activity, flow and lung volume. Lung function and transcutaneous electromyography of the respiratory muscles (rEMG) were measured in 20 infants with CLD and in 39 healthy age-matched controls during quiet sleep. We compared coefficient of variations (CVs) of rEMG and the temporal relationship of rEMG variables, to flow and lung volume [functional residual capacity (FRC)] between these groups. The time between the start of inspiratory muscle activity and the resulting flow (tria)--in relation to respiratory cycle time--was significantly longer in infants with CLD. Although FRC had similar associations with tria and postinspiratory activity (corrected for respiratory cycle time), the CV of the diaphragmatic rEMG was lower in CLD infants (22.6 versus 31.0%, p = 0.030). The temporal relationship of rEMG to flow and FRC and the loss of adaptive variability provide additional information on coping mechanisms in infants with CLD. This technique could be used for noninvasive bedside monitoring of CLD.

Seeing and identifying with a virtual body decreases pain perception

Pain and the conscious mind (or the self) are experienced in our body. Both are intimately linked to the subjective quality of conscious experience. Here, we used virtual reality technology and visuo-tactile conflicts in healthy subjects to test whether experimentally induced changes of bodily self-consciousness (self-location; self-identification) lead to changes in pain perception. We found that visuo-tactile stroking of a virtual body but not of a control object led to increased pressure pain thresholds and self-location. This increase was not modulated by the synchrony of stroking as predicted based on earlier work. This differed for self-identification where we found as predicted that synchrony of stroking increased self-identification with the virtual body (but not a control object), and positively correlated with an increase in pain thresholds. We discuss the functional mechanisms of self-identification, self-location, and the visual perception of human bodies with respect to pain perception.

Short- and long-term immunological and virological outcome in HIV-infected infants according to the age at antiretroviral treatment initiation

The clinical benefit of antiretroviral therapy in infants is established. In this cohort collaboration, we compare immunological and virological response to treatment started before or after 3 months of age. Early initiation provides a better short-term response, although evolution after 12 months of age is similar in both groups.