Attention induced distortions of neural population responses, receptive fields, and tuning curves

Selektive visuelle Aufmerksamkeit bezeichnet im Allgemeinen die zielgerichtete Steuerung des Informationsflusses. Zahlreiche Studien im Bereich der raum- und merkmalsbasierten Aufmerksamkeit haben gezeigt, dass das visuelle System diese Kontrolle durch aktivitätsmodulierende Mechanismen ausübt. Es wird angenommen, dass diese Mechanismen zu einer verstärkten neuronalen Repräsentation von relevanten Stimuli oder Merkmalen führen, während irrelevante Aspekte unterdrückt werden. Dies bedeutet, dass Aufmerksamkeit lediglich die Stärke der neuronalen Repräsentationen, nicht aber die repräsentierten Inhalte selbst ändert. In dieser Arbeit wird argumentiert, dass Aufmerksamkeit die neuronalen Repräsentationen grundlegend sowohl auf Populationsebene als auch auf der Ebene einzelner Neurone verändern kann. Dies wird anhand offener Aufmerksamkeitsverlagerungen und der Ausrichtung von merkmalsbasierter Aufmerksamkeit gezeigt werden. Selective visual attention is generally conceptualized to control the flow of information with respect to the task at hand. Various studies in the space-based and feature-based domain of attention have demonstrated that the visual system achieves this via gain-control mechanisms. These mechanisms are supposed to result in an enhanced neural representation of relevant stimuli or features while irrelevant ones are suppressed. Thus, attention is suggested to modulate the strength of neural representations without altering their content. In this thesis, however, it will be argued that attention is able to change the very nature of these neural representations both at the level of population responses and of single neurons. This will be demonstrated for overt shifts of space-based attention as well as for the directing of feature-based attention

Xq27.1 palindrome mediated interchromosomal insertion likely causes familial congenital bilateral laryngeal abductor paralysis (Plott syndrome)

Bilateral laryngeal abductor paralysis is a rare entity and the second most common cause of stridor in newborns. So far, no conclusive genetic or chromosomal aberration has been reported for X-linked isolated bilateral vocal cord paralysis, also referred to as Plott syndrome. Via whole genome sequencing (WGS), we identified a complex interchromosomal insertion in a large family with seven affected males. The 404 kb inserted fragment originates from chromosome 10q21.3, contains no genes and is inserted inversionally into the intergenic chromosomal region Xq27.1, 82 kb centromeric to the nearest gene SOX3. The patterns found at the breakpoint junctions resemble typical characteristics that arise in replication-based mechanisms with long-distance template switching. Non protein-coding insertions into the same genomic region have been described to result in different phenotypes, indicating that the phenotypic outcome likely depends on the introduction of regulatory elements. In conclusion, our data adds Plott syndrome as another entity, likely caused by the insertion of non-coding DNA into the intergenic chromosomal region Xq27.1. In this regard, we demonstrate the importance of WGS as a powerful diagnostic test in unsolved genetic diseases, as this genomic rearrangement has not been detected by current first-line diagnostic tests, i.e., exome sequencing and chromosomal microarray analysis

Parietal Cortex Regulates Visual Salience and Salience-Driven Behavior

Chen et al. show that inactivation of parietal cortex selectively reduces salience signals within prefrontal cortex and diminishes the influence of salience on visually guided behavior. The results demonstrate a causal role of parietal cortex in regulating salience signals within the brain and in controlling salience-driven behavior

VarFish - Collaborative and comprehensive variant analysis for diagnosis and research

VarFish is a user-friendly web application for the quality control, filtering, prioritization, analysis, and user-based annotation of panel and exome variant data for rare disease genetics. It is capable of processing variant call files with single or multiple samples. The variants are automatically annotated with population frequencies, molecular impact, and presence in databases such as ClinVar. Further, it provides support for pathogenicity scores including CADD, MutationTaster, and phenotypic similarity scores. Users can filter variants based on these annotations and presumed inheritance pattern and sort the results by these scores. Filtered variants are listed with their annotations and many useful link-outs to genome browsers, other gene/variant data portals, and external tools for variant assessment. VarFish allows user to create their own annotations including support for variant assessment following ACMG-AMP guidelines. In close collaboration with medical practitioners, VarFish was designed for variant analysis and prioritization in diagnostic and research settings as described in the software’s extensive manual. The user interface has been optimized for supporting these protocols. Users can install VarFish on their own in-house servers where it provides additional lab notebook features for collaborative analysis and allows re-analysis of cases, e.g., after update of genotype or phenotype databases

The Contribution of Parietal Cortex to Visual Salience

Unique stimuli stand out. In spite of an abundance of competing sensory stimuli, the detection of the most salient ones occurs without effort, and that detection contributes to the guidance of adaptive behavior. Neurons sensitive to the salience of visual stimuli are widespread throughout the primate visual system and are thought to shape the selection of visual targets. However, the source of the salience computation has remained elusive. Among the possible candidates are areas within posterior parietal cortex, which appear to be crucial in the control of visual attention and are thought to play a unique role in representing stimulus salience. Here we show that reversible inactivation of parietal cortex not only selectively reduces the representation of visual salience within the brain, but it also diminishes the influence of salience on visually guided behavior. These results demonstrate a distinct contribution of parietal areas to vision and visual attention

The Contribution of Parietal Cortex to Visual Salience

Unique stimuli stand out. In spite of an abundance of competing sensory stimuli, the detection of the most salient ones occurs without effort, and that detection contributes to the guidance of adaptive behavior. Neurons sensitive to the salience of visual stimuli are widespread throughout the primate visual system and are thought to shape the selection of visual targets. However, the source of the salience computation has remained elusive. Among the possible candidates are areas within posterior parietal cortex, which appear to be crucial in the control of visual attention and are thought to play a unique role in representing stimulus salience. Here we show that reversible inactivation of parietal cortex not only selectively reduces the representation of visual salience within the brain, but it also diminishes the influence of salience on visually guided behavior. These results demonstrate a distinct contribution of parietal areas to vision and visual attention

P5CS expression study in a new family with ALDH18A1-associated hereditary spastic paraplegia SPG9

In 2015\u20132016, we and others reported ALDH18A1 mutations causing dominant (SPG9A) or recessive (SPG9B) spastic paraplegia. In vitro production of the ALDH18A1 product, \u3941-pyrroline-5-carboxylate synthetase (P5CS), appeared necessary for cracking SPG9 disease-causing mechanisms. We now describe a baculovirus\u2013insect cell system that yields mgs of pure human P5CS and that has proven highly valuable with two novel P5CS mutations reported here in new SPG9B patients. We conclude that both mutations are disease-causing, that SPG9B associates with partial P5CS deficiency and that it is clinically more severe than SPG9A, as reflected in onset age, disability, cognitive status, growth, and dysmorphic traits

Complete lung agenesis caused by complex genomic rearrangements with neo-TAD formation at the SHH locus

During human organogenesis, lung development is a timely and tightly regulated developmental process under the control of a large number of signaling molecules. Understanding how genetic variants can disturb normal lung development causing different lung malformations is a major goal for dissecting molecular mechanisms during embryogenesis. Here, through exome sequencing (ES), array CGH, genome sequencing (GS) and Hi-C, we aimed at elucidating the molecular basis of bilateral isolated lung agenesis in three fetuses born to a non-consanguineous family. We detected a complex genomic rearrangement containing duplicated, triplicated and deleted fragments involving the SHH locus in fetuses presenting complete agenesis of both lungs and near-complete agenesis of the trachea, diagnosed by ultrasound screening and confirmed at autopsy following termination. The rearrangement did not include SHH itself, but several regulatory elements for lung development, such as MACS1, a major SHH lung enhancer, and the neighboring genes MNX1 and NOM1. The rearrangement incorporated parts of two topologically associating domains (TADs) including their boundaries. Hi-C of cells from one of the affected fetuses showed the formation of two novel TADs each containing SHH enhancers and the MNX1 and NOM1 genes. Hi-C together with GS indicate that the new 3D conformation is likely causative for this condition by an inappropriate activation of MNX1 included in the neo-TADs by MACS1 enhancer, further highlighting the importance of the 3D chromatin conformation in human disease

Mislocalization of Visual Stimuli: Independent Effects of Static and Dynamic Attention

Shifts of visual attention cause systematic distortions of the perceived locations of visual objects around the focus of attention. In the attention repulsion effect, the perceived location of a visual target is shifted away from an attention-attracting cue when the cue is presented before the target. Recently it has been found that, if the visual cue is presented after the target, the perceived location of the target shifts toward the location of the following cue. One unanswered question is whether a single mechanism underlies both attentional repulsion and attraction effects. We presented participants with two disks at diagonal locations as visual cues and two vertical lines as targets. Participants were asked to perform a forced-choice task to judge targets' positions. The present study examined whether the magnitude of the repulsion effect and the attraction effect would differ (Experiment 1), whether the two effects would interact (Experiment 2), and whether the location or the dynamic shift of attentional focus would determine the distortions effects (Experiment 3). The results showed that the effect size of the attraction effect was slightly larger than the repulsion effect and the preceding and following cues have independent influences on the perceived positions. The repulsion effect was caused by the location of attnetion and the attraction effect was due to the dynamic shift of attentional focus, suggesting that the underlying mechanisms for the retrospective attraction effect might be different from those for the repulsion effect