Reducing instability of inter-subject covariance of FDG uptake networks using structure-weighted sparse estimation approach.

PURPOSE: Sparse inverse covariance estimation (SICE) is increasingly utilized to estimate inter-subject covariance of FDG uptake (FDGcov) as proxy of metabolic brain connectivity. However, this statistical method suffers from the lack of robustness in the connectivity estimation. Patterns of FDGcov were observed to be spatially similar with patterns of structural connectivity as obtained from DTI imaging. Based on this similarity, we propose to regularize the sparse estimation of FDGcov using the structural connectivity. METHODS: We retrospectively analyzed the FDG-PET and DTI data of 26 healthy controls, 41 patients with Alzheimer's disease (AD), and 30 patients with frontotemporal lobar degeneration (FTLD). Structural connectivity matrix derived from DTI data was introduced as a regularization parameter to assign individual penalties to each potential metabolic connectivity. Leave-one-out cross validation experiments were performed to assess the differential diagnosis ability of structure weighted SICE approach. A few approaches of structure weighted were compared with the standard SICE. RESULTS: Compared to the standard SICE, structural weighting has shown more stable performance in the supervised classification, especially in the differentiation AD vs. FTLD (accuracy of 89-90%, while unweighted SICE only 85%). There was a significant positive relationship between the minimum number of metabolic connection and the robustness of the classification accuracy (r = 0.57, P < 0.001). Shuffling experiments showed significant differences between classification score derived with true structural weighting and those obtained by randomized structure (P < 0.05). CONCLUSION: The structure-weighted sparse estimation can enhance the robustness of metabolic connectivity, which may consequently improve the differentiation of pathological phenotypes.

Mapping covariance in brain FDG uptake to structural connectivity.

PURPOSE: Inter-subject covariance of regional 18F-fluorodeoxyglucose (FDG) PET measures (FDGcov) as proxy of brain connectivity has been gaining an increasing acceptance in the community. Yet, it is still unclear to what extent FDGcov is underlied by actual structural connectivity via white matter fiber tracts. In this study, we quantified the degree of spatial overlap between FDGcov and structural connectivity networks. METHODS: We retrospectively analyzed neuroimaging data from 303 subjects, both patients with suspected neurodegenerative disorders and healthy individuals. For each subject, structural magnetic resonance, diffusion tensor imaging, and FDG-PET data were available. The images were spatially normalized to a standard space and segmented into 62 anatomical regions using a probabilistic atlas. Sparse inverse covariance estimation was employed to estimate FDGcov. Structural connectivity was measured by streamline tractography through fiber assignment by continuous tracking. RESULTS: For the whole brain, 55% of detected connections were found to be convergent, i.e., present in both FDGcov and structural networks. This metric for random networks was significantly lower, i.e., 12%. Convergent were 80% of intralobe connections and only 30% of interhemispheric interlobe connections. CONCLUSION: Structural connectivity via white matter fiber tracts is a relevant substrate of FDGcov, underlying around a half of connections at the whole brain level. Short-range white matter tracts appear to be a major substrate of intralobe FDGcov connections.

Acoustically driven orientation and navigation in enclosed spaces.

Awareness of space, and subsequent orientation and navigation in rooms, is dominated by the visual system. However, humans are able to extract auditory information about their surroundings from early reflections and reverberation in enclosed spaces. To better understand orientation and navigation based on acoustic cues only, three virtual corridor layouts (I-, U-, and Z-shaped) were presented using real-time virtual acoustics in a three-dimensional 86-channel loudspeaker array. Participants were seated on a rotating chair in the center of the loudspeaker array and navigated using real rotation and virtual locomotion by "teleporting" in steps on a grid in the invisible environment. A head mounted display showed control elements and the environment in a visual reference condition. Acoustical information about the environment originated from a virtual sound source at the collision point of a virtual ray with the boundaries. In different control modes, the ray was cast either in view or hand direction or in a rotating, "radar"-like fashion in 90° steps to all sides. Time to complete, number of collisions, and movement patterns were evaluated. Navigation and orientation were possible based on the direct sound with little effect of room acoustics and control mode. Underlying acoustic cues were analyzed using an auditory model.

Psychophysical evidence for auditory motion parallax.

Distance is important: From an ecological perspective, knowledge about the distance to either prey or predator is vital. However, the distance of an unknown sound source is particularly difficult to assess, especially in anechoic environments. In vision, changes in perspective resulting from observer motion produce a reliable, consistent, and unambiguous impression of depth known as motion parallax. Here we demonstrate with formal psychophysics that humans can exploit auditory motion parallax, i.e., the change in the dynamic binaural cues elicited by self-motion, to assess the relative depths of two sound sources. Our data show that sensitivity to relative depth is best when subjects move actively; performance deteriorates when subjects are moved by a motion platform or when the sound sources themselves move. This is true even though the dynamic binaural cues elicited by these three types of motion are identical. Our data demonstrate a perceptual strategy to segregate intermittent sound sources in depth and highlight the tight interaction between self-motion and binaural processing that allows assessment of the spatial layout of complex acoustic scenes.

The percept of reverberation is not affected by visual room impression in virtual environments.

Humans possess mechanisms to suppress distracting early sound reflections, summarized as the precedence effect. Recent work shows that precedence is affected by visual stimulation. This paper investigates possible effects of visual stimulation on the perception of later reflections, i.e., reverberation. In a highly immersive audio-visual virtual reality environment, subjects were asked to quantify reverberation in conditions where simultaneously presented auditory and visual stimuli either match in room identity, sound source azimuth, and sound source distance, or diverge in one of these aspects. While subjects reliably judged reverberation across acoustic environments, the visual room impression did not affect reverberation estimates.

Health Applications for Corporate Health Management.

INTRODUCTION: Many corporate organizations around the world are looking at new ways to improve the health and well-being of their employees. Many have begun to use m-health approaches and unique applications (apps) to provide assistance. In Germany, both m-health and occupational health management (OHM) are growing quickly. Therefore, we hypothesized that the combination-apps usage in OHM-is growing as well. We studied the usage of health apps in large corporations for health management of employed individuals. METHODS: To understand the environment in Germany, a two-part study was conducted. First, an extensive literature search was done and second, interviews were conducted with 12 of the 20 biggest companies' health management representatives. RESULTS: Using key search terms, 5,445 peer-reviewed journal articles traced with German databases and on PubMed were reviewed. Interestingly and somewhat surprising to the authors, none of them covered our specific topic. Interviews were conducted with 60% of the companies indicated. Only 3 out of 12 companies use apps. Four companies are piloting apps. With one exception, apps cover well-known areas such as food coaching, physical motion, smoking cessation, stress prevention, and other health-related subjects. One app used sensors in work clothing to prevent unhealthy motion. With a few exceptions, there has been no evaluation of the utility and utilization of apps. DISCUSSION: Current app usage in corporate health management in Germany is surprisingly low. Apps need to be better evaluated. Main obstacles-which could be resolved in the future-are legal restrictions (especially on data security), the lack of company-owned smart phones, misfit of apps and corporate health strategy, a lack of app evaluation, and high app prices.

Auditory orientation and distance estimation of sighted humans using virtual echolocation with artificial and self-generated sounds.

Active echolocation of sighted humans using predefined synthetic and self-emitted sounds, as habitually used by blind individuals, was investigated. Using virtual acoustics, distance estimation and directional localization of a wall in different rooms were assessed. A virtual source was attached to either the head or hand with realistic or increased source directivity. A control condition was tested with a virtual sound source located at the wall. Untrained echolocation performance comparable to performance in the control condition was achieved on an individual level. On average, the echolocation performance was considerably lower than in the control condition, however, it benefitted from increased directivity.

Frequency modulation of rattlesnake acoustic display affects acoustic distance perception in humans.

The estimation of one's distance to a potential threat is essential for any animal's survival. Rattlesnakes inform about their presence by generating acoustic broadband rattling sounds.1 Rattlesnakes generate their acoustic signals by clashing a series of keratinous segments onto each other, which are located at the tip of their tails.1-3 Each tail shake results in a broadband sound pulse that merges into a continuous acoustic signal with fast-repeating tail shakes. This acoustic display is readily recognized by other animals4,5 and serves as an aposematic threat and warning display, likely to avoid being preyed upon.1,6 The spectral properties of the rattling sound1,3 and its dependence on the morphology and size of the rattle have been investigated for decades7-9 and carry relevant information for different receivers, including ground squirrels that encounter rattlesnakes regularly.10,11 Combining visual looming stimuli with acoustic measurements, we show that rattlesnakes increase their rattling rate (up to about 40 Hz) with decreasing distance of a potential threat, reminiscent of the acoustic signals of sensors while parking a car. Rattlesnakes then abruptly switch to a higher and less variable rate of 60-100 Hz. In a virtual reality experiment, we show that this behavior systematically affects distance judgments by humans: the abrupt switch in rattling rate generates a sudden, strong percept of decreased distance which, together with the low-frequency rattling, acts as a remarkable interspecies communication signal. VIDEO ABSTRACT.

The vocal development of the pale spear-nosed bat is dependent on auditory feedback.

Human vocal development and speech learning require acoustic feedback, and humans who are born deaf do not acquire a normal adult speech capacity. Most other mammals display a largely innate vocal repertoire. Like humans, bats are thought to be one of the few taxa capable of vocal learning as they can acquire new vocalizations by modifying vocalizations according to auditory experiences. We investigated the effect of acoustic deafening on the vocal development of the pale spear-nosed bat. Three juvenile pale spear-nosed bats were deafened, and their vocal development was studied in comparison with an age-matched, hearing control group. The results show that during development the deafened bats increased their vocal activity, and their vocalizations were substantially altered, being much shorter, higher in pitch, and more aperiodic than the vocalizations of the control animals. The pale spear-nosed bat relies on auditory feedback for vocal development and, in the absence of auditory input, species-atypical vocalizations are acquired. This work serves as a basis for further research using the pale spear-nosed bat as a mammalian model for vocal learning, and contributes to comparative studies on hearing impairment across species. This article is part of the theme issue 'Vocal learning in animals and humans'.

Effects of neonatal lesions of the medial prefrontal cortex on adult rat behaviour.

While prefrontal lesions in rodents serve as models for frontal lobe syndromes, neonatal lesions are considered as models for disconnection syndromes, such as schizophrenia. We investigated the effect of neonatal lesions of the rat medial prefrontal cortex (mPFC) together with pubertal dexamethasone-challenge on adult rat behaviour and on apomorphine-induced behavioural changes. Adult lesions were used as controls. Rats with neonatal (postnatal day 7) or adult excitotoxic lesions or sham-lesions of the mPFC were tested 9 weeks after surgery. At postnatal day 49 one group of neonatal operated rats were systemically injected with the glucocorticoid receptor agonist dexamethasone (20 mg/kg), in order to simulate stress-induced glucocorticoid receptor activation. Working memory and perseveration was tested in T-maze tasks (continuous delayed alternation and reversal learning). Additionally, locomotor activity and prepulse inhibition (PPI) of startle was tested with and without apomorphine-treatment. Brain tissue damage was assessed using Nissl-staining and parvalbumine-immunocytochemistry. Pronounced thinning of the prelimbic-infralimbic subregion of the mPFC accompanied by altered cytoarchitecture and reduced number of parvalbumine-immunopositive neurones was found after neonatal lesions while adult lesions resulted in loss of neurones accompanied by gliosis. Neonatal lesions increased perseveration in the T-maze tasks and enhanced PPI, while adult lesions induced a working memory deficit. This differential behavioural outcome presumably reflects neurodevelopmentally induced alterations in neuronal circuits after neonatal lesions versus damage to mPFC alone after adult lesions. Dexamethasone-injection at day 49 did not alter behaviour in these tasks. Motor activity was not affected by neonatal or adult lesions but dexamethasone reduced apomorphine-induced hyperlocomotion.

Changes in connexin43 in early ocular surface development.

PURPOSE: In the limbo-corneal epithelium the stem and early precursor epithelial cell pool is confined to the limbal rim. Among the features associated with this spatial segregation is the general paucity of connexin43 (Cx43) within the limbal basal cell population and its complete absence in resident stem cells. The limbo-corneal epithelial lineage derives from a Cx43-positive (Cx43+) embryonic outer ectoderm. Accordingly, as a means of identifying the process through which limbal cell phenotypes emerge, we investigated the expression of Cx43 in the ocular surface of embryonic rats. METHODS: Ocular surface expression of Cx43 or K12 was determined in cryostat sections of rat embryos and eyes using immunohistological methods. RESULTS: Changes in Cx43 expression revealed the early phenotypic divergence of three main epithelial cell phenotypes of the ocular surface. An analysis of the level and distribution pattern of Cx43 puncta lead to the identification of two distinct domains by embryonic day 10 (E10), a stage that occurs soon after formation of the lens vesicle. Additionally, at E12, ectodermal cells directly adjacent to the edges of the developing retina no longer express connexin. A comparison of anatomical and expression changes throughout embryonic development demonstrated that the two early zones represent the rudiments for the epithelia of the central cornea and conjunctiva, respectively, and that the isolated Cx43-negative (Cx43-) cells represent the precursors of the basal and, putatively, stem cells of the limbal epithelium. CONCLUSIONS: Changes in Cx43 expression revealed that the phenotypic divergence of ocular surface epithelial cells and the generation of limbo-corneal stem cell precursors takes place at a very early stage in ocular development, ahead of the establishment of any identifiable anatomical or differentiation features for these domains.

[Communication of psychiatric hospitals' specialization]. / Kommunikation von Behandlungsschwerpunkten psychiatrischer Kliniken.

OBJECTIVE: To analyze whether specialization of psychiatric hospitals results in quality improvement, and whether it can and should be measured and communicated to patients and ambulatory care physicians. METHODS: Depth interviews with key deciders in the German psychiatric care system. RESULTS: There are several specializations within the system of psychiatric hospital care which can be communicated to patients and physicians; this would facilitate choice of hospital. There is no national database available yet. CONCLUSIONS: Data collection and communication as provided by an independent organization would improve knowledge about hospital specialization.