Common and distinct neural correlates of trial-by-trial expectancies for feature-based as compared to spatial attention

Since our brain can only process a small amount of sensory information at a time, attention systems select specific aspects for prioritized processing – such as features or locations – that are expected to be most relevant in a given context. The present thesis investigated responses of visual attention systems to expected and unexpected sensory events during uncertainty, when the probability of sensory events needs to be inferred from environmental observations. In the spatial attention domain these processes have already been described with the help of computational models and the underlying neural mechanisms have been explored with functional neuroimaging. However, it is not known whether other attentional subsystems such as feature-based attention behave similarly during uncertainty. The core aim of this thesis was to characterize the modulation of attentional deployment by inferred probabilities during feature-based as compared to spatial attention. This was realized using a Posner-cueing paradigm in which feature and spatial cues were presented. Classically these cues predict the color or the location of an upcoming target with a fixed high probability, so that participants expect the cues to be valid and respond slower and less accurate when attention needs to be reoriented to invalidly cued targets. In the present paradigm, this probability was varied by changing the percentage cue validity (%CV) unpredictably over time. In a behavioral experiment (Experiment 1) three different color cues were used to identify cue-related factors which influence the effects of probabilistic inference on feature-based attention and to establish an experimental paradigm for the comparison of feature-based and spatial attention systems. It was observed that all color cues affected attentional deployment. However, probability-dependent effects differed depending on the level of cue abstraction: More automatically processed cues required more observations of cue-target outcomes to establish probabilistic learning than abstract cues. Experiment 2 employed functional magnetic resonance imaging (fMRI) to investigate the computational and neural mechanisms that modulate probabilistic inference using the experimental paradigm from Experiment 1 with abstract feature and spatial cues. The results indicated that probabilistic inference follows similar principles for both attention systems. However, their neural implementations seemed to be confined to domain-specific subsystems: The right temporoparietal junction (TPJ) was particularly involved in spatial attention, while the left intraparietal sulcus (IPS) was most crucial for feature-based attention. However, the left anterior IPS showed an effect of probability-dependent attention in both attention systems. These findings provide novel insights into the generality and specificity of the functional basis of visual attention, suggesting that probabilistic inference can distinctively affect each attentional subsystem, but that the left anterior IPS may establish probabilistic inference in a domain general manner. Taken together our findings speak against a unitary visual attention network. Rather, we propose that depending on the nature of the selected aspects different attentional subsystems are activated following expectancy violations and these processes can even differ within one single domain such as feature-based attention

Men Presenting With Sexual Thoughts of Children or Coercion: Flights of Fancy or Plans for Crime?

Introduction. There is limited evaluation of clinical and theoretical claims that sexual thoughts of children and coercing others facilitate sexual offending. The nature of these thoughts (what they contain) is also unknown. Aims. To examine the relationship between child/coercive sexual thoughts and sexual offending, and to determine the nature of these thoughts and any differences between sexual offending (SO), non-sexual offending (NSO) and non-offending (NO) men. Methods. In a cross-sectional computerized survey, anonymous qualitative and quantitative self-reported sexual thought and experience data were collected from 279 adult volunteers, comprising equal numbers of SO, NSO and NO men recruited from a medium-security UK prison and a community sample of 6081 men. Main Outcome Measures. Computerized Interview for Sexual Thoughts and Computerized Inventory of Sexual Experiences. Results. Three analytical approaches found child sexual thoughts were related to sexual offending; sexual thoughts with coercive themes were not. Latent class analyses identified three types of child sexual thought (primarily differentiated by interpersonal context: the reporting of own emotions, emotions of others or both) and four types of sexual thoughts of coercing others (chiefly discriminated by the other person’s response: no emotional states reported, consent, non-consent, mixed). Type of child sexual thought and participant group were not significantly related. Type of coercive sexual thought and group were marginally related; the consensual type was more common for the NO group, the non-consensual type more common for the SO group, than expected statistically. Conclusions. Child sexual thoughts are a risk factor for sexual offending and should be assessed by clinicians. Generally, sexual thoughts with coercive themes are not a risk factor, though thought type may be important (i.e. thoughts where the other person expresses an enduring lack of consent). Exploring the dynamic risk factors associated with each type of child/coercive thought may lead to more targeted treatment

Design of Photovoltaic Microinverter for Off-Grid and Grid-Parallel Applications

Proceedings der Konferenz "8th International Conference on Integrated Power Electronics Systems" CIPS 2014, gehalten vom 25.-27. Februar 2014 in Nürnberg

Lesions to the Fronto-Parietal Network Impact Alpha-Band Phase Synchrony and Cognitive Control.

Long-range phase synchrony in the α-oscillation band (near 10 Hz) has been proposed to facilitate information integration across anatomically segregated regions. Which areas may top-down regulate such cross-regional integration is largely unknown. We previously found that the moment-to-moment strength of high-α band (10-12 Hz) phase synchrony co-varies with activity in a fronto-parietal (FP) network. This network is critical for adaptive cognitive control functions such as cognitive flexibility required during set-shifting. Using electroencephalography (EEG) in 23 patients with focal frontal lobe lesions (resected tumors), we tested the hypothesis that the FP network is necessary for modulation of high-α band phase synchrony. Global phase-synchrony was measured using an adaptation of the phase-locking value (PLV) in a sliding window procedure, which allowed for measurement of changes in EEG-based resting-state functional connectivity across time. As hypothesized, the temporal modulation (range and standard deviation) of high-α phase synchrony was reduced as a function of FP network lesion extent, mostly due to dorsolateral prefrontal cortex (dlPFC) lesions. Furthermore, patients with dlPFC lesions exhibited reduced cognitive flexibility as measured by the Trail-Making Test (set-shifting). Our findings provide evidence that the FP network is necessary for modulatory control of high-α band long-range phase synchrony, and linked to cognitive flexibility

The hnRNP family: insights into their role in health and disease

Heterogeneous nuclear ribonucleoproteins (hnRNPs) represent a large family of RNA-binding proteins (RBPs) that contribute to multiple aspects of nucleic acid metabolism including alternative splicing, mRNA stabilization, and transcriptional and translational regulation. Many hnRNPs share general features, but differ in domain composition and functional properties. This review will discuss the current knowledge about the different hnRNP family members, focusing on their structural and functional divergence. Additionally, we will highlight their involvement in neurodegenerative diseases and cancer, and the potential to develop RNA-based therapies

Neurofilament depletion improves microtubule dynamics via modulation of Stat3/stathmin signaling

In neurons, microtubules form a dense array within axons, and the stability and function of this microtubule network is modulated by neurofilaments. Accumulation of neurofilaments has been observed in several forms of neurodegenerative diseases, but the mechanisms how elevated neurofilament levels destabilize axons are unknown so far. Here, we show that increased neurofilament expression in motor nerves of pmn mutant mice, a model of motoneuron disease, causes disturbed microtubule dynamics. The disease is caused by a point mutation in the tubulin-specific chaperone E (Tbce) gene, leading to an exchange of the most C-terminal amino acid tryptophan to glycine. As a consequence, the TBCE protein becomes instable which then results in destabilization of axonal microtubules and defects in axonal transport, in particular in motoneurons. Depletion of neurofilament increases the number and regrowth of microtubules in pmn mutant motoneurons and restores axon elongation. This effect is mediated by interaction of neurofilament with the stathmin complex. Accumulating neurofilaments associate with stathmin in axons of pmn mutant motoneurons. Depletion of neurofilament by Nefl knockout increases Stat3-stathmin interaction and stabilizes the microtubules in pmn mutant motoneurons. Consequently, counteracting enhanced neurofilament expression improves axonal maintenance and prolongs survival of pmn mutant mice. We propose that this mechanism could also be relevant for other neurodegenerative diseases in which neurofilament accumulation and loss of microtubules are prominent features

Axonal and dendritic localization of mRNAs for glycogen-metabolizing enzymes in cultured rodent neurons

Background: Localization of mRNAs encoding cytoskeletal or signaling proteins to neuronal processes is known to contribute to axon growth, synaptic differentiation and plasticity. In addition, a still increasing spectrum of mRNAs has been demonstrated to be localized under different conditions and developing stages thus reflecting a highly regulated mechanism and a role of mRNA localization in a broad range of cellular processes. Results: Applying fluorescence in-situ-hybridization with specific riboprobes on cultured neurons and nervous tissue sections, we investigated whether the mRNAs for two metabolic enzymes, namely glycogen synthase (GS) and glycogen phosphorylase (GP), the key enzymes of glycogen metabolism, may also be targeted to neuronal processes. If it were so, this might contribute to clarify the so far enigmatic role of neuronal glycogen. We found that the mRNAs for both enzymes are localized to axonal and dendritic processes in cultured lumbar spinal motoneurons, but not in cultured trigeminal neurons. In cultured cortical neurons which do not store glycogen but nevertheless express glycogen synthase, the GS mRNA is also subject to axonal and dendritic localization. In spinal motoneurons and trigeminal neurons in situ, however, the mRNAs could only be demonstrated in the neuronal somata but not in the nerves. Conclusions: We could demonstrate that the mRNAs for major enzymes of neural energy metabolism can be localized to neuronal processes. The heterogeneous pattern of mRNA localization in different culture types and developmental stages stresses that mRNA localization is a versatile mechanism for the fine-tuning of cellular events. Our findings suggest that mRNA localization for enzymes of glycogen metabolism could allow adaptation to spatial and temporal energy demands in neuronal events like growth, repair and synaptic transmission