Divisive Normalization and Neuronal Oscillations in a Single Hierarchical Framework of Selective Visual Attention

Divisive normalization models of covert attention commonly use spike rate modulations as indicators of the effect of top-down attention. In addition, an increasing number of studies have shown that top-down attention increases the synchronization of neuronal oscillations as well, particularly in gamma-band frequencies (25–100 Hz). Although modulations of spike rate and synchronous oscillations are not mutually exclusive as mechanisms of attention, there has thus far been little effort to integrate these concepts into a single framework of attention. Here, we aim to provide such a unified framework by expanding the normalization model of attention with a multi-level hierarchical structure and a time dimension; allowing the simulation of a recently reported backward progression of attentional effects along the visual cortical hierarchy. A simple cascade of normalization models simulating different cortical areas is shown to cause signal degradation and a loss of stimulus discriminability over time. To negate this degradation and ensure stable neuronal stimulus representations, we incorporate a kind of oscillatory phase entrainment into our model that has previously been proposed as the “communication-through-coherence” (CTC) hypothesis. Our analysis shows that divisive normalization and oscillation models can complement each other in a unified account of the neural mechanisms of selective visual attention. The resulting hierarchical normalization and oscillation (HNO) model reproduces several additional spatial and temporal aspects of attentional modulation and predicts a latency effect on neuronal responses as a result of cued attention

Usability of Three-dimensional Augmented Visual Cues Delivered by Smart Glasses on (Freezing of) Gait in Parkinson’s Disease

External cueing is a potentially effective strategy to reduce freezing of gait (FOG) in persons with Parkinson’s disease (PD). Case reports suggest that three-dimensional (3D) cues might be more effective in reducing FOG than two-dimensional cues. We investigate the usability of 3D augmented reality visual cues delivered by smart glasses in comparison to conventional 3D transverse bars on the floor and auditory cueing via a metronome in reducing FOG and improving gait parameters. In laboratory experiments, 25 persons with PD and FOG performed walking tasks while wearing custom-made smart glasses under five conditions, at the end-of-dose. For two conditions, augmented visual cues (bars/staircase) were displayed via the smart glasses. The control conditions involved conventional 3D transverse bars on the floor, auditory cueing via a metronome, and no cueing. The number of FOG episodes and percentage of time spent on FOG were rated from video recordings. The stride length and its variability, cycle time and its variability, cadence, and speed were calculated from motion data collected with a motion capture suit equipped with 17 inertial measurement units. A total of 300 FOG episodes occurred in 19 out of 25 participants. There were no statistically significant differences in number of FOG episodes and percentage of time spent on FOG across the five conditions. The conventional bars increased stride length, cycle time, and stride length variability, while decreasing cadence and speed. No effects for the other conditions were found. Participants preferred the metronome most, and the augmented staircase least. They suggested to improve the comfort, esthetics, usability, field of view, and stability of the smart glasses on the head and to reduce their weight and size. In their current form, augmented visual cues delivered by smart glasses are not beneficial for persons with PD and FOG. This could be attributable to distraction, blockage of visual feedback, insufficient familiarization with the smart glasses, or display of the visual cues in the central rather than peripheral visual field. Future smart glasses are required to be more lightweight, comfortable, and user friendly to avoid distraction and blockage of sensory feedback, thus increasing usability

The effect of doorway characteristics on freezing of gait in Parkinson’s disease

BackgroundFreezing of gait is a debilitating symptom in Parkinson’s disease, during which a sudden motor block prevents someone from moving forward. Remarkably, doorways can provoke freezing. Most research has focused on the influence of doorway width, and little is known about other doorway characteristics influencing doorway freezing.ObjectiveFirstly, to provide guidelines on how to design doorways for people with freezing. Secondly, to compare people with doorway freezing to people without doorway freezing, and to explore the underlying mechanisms of doorway freezing.MethodsWe designed a web-based, structured survey consisting of two parts. Part I (n = 171 responders), open to people with Parkinson’s disease with freezing in general, aimed to compare people with doorway freezing to people without doorway freezing. We explored underlying processes related to doorway freezing with the Gait-Specific Attention Profile (G-SAP), inquiring about conscious movement processes occurring during doorway passing. Part II (n = 60), open for people experiencing weekly doorway freezing episodes, inquired about the influence of specific doorway characteristics on freezing.ResultsPeople with doorway freezing (69% of Part I) had higher freezing severity, longer disease duration, and scored higher on all sub scores of the G-SAP (indicating heightened motor, attentional, and emotional thoughts when passing through doorways) than people without doorway freezing. The main categories provoking doorway freezing were: dimensions of the door and surroundings, clutter around the door, lighting conditions, and automatic doors.ConclusionWe provide recommendations on how to maximally avoid freezing in a practical setting. Furthermore, we suggest that doorways trigger freezing based on visuomotor, attentional, and emotional processes

Cerebral autoregulation assessed by near-infrared spectroscopy:validation using transcranial Doppler in patients with controlled hypertension, cognitive impairment and controls

PURPOSE: Cerebral autoregulation (CA) aims to attenuate the effects of blood pressure variation on cerebral blood flow. This study assessed the criterion validity of CA derived from near-infrared spectroscopy (NIRS) as an alternative for Transcranial Doppler (TCD). METHODS: Measurements of continuous blood pressure (BP), oxygenated hemoglobin (O(2)Hb) using NIRS and cerebral blood flow velocity (CBFV) using TCD (gold standard) were performed in 82 controls, 27 patients with hypertension and 94 cognitively impaired patients during supine rest (all individuals) and repeated sit to stand transitions (cognitively impaired patients). The BP-CBFV and BP-O(2)Hb transfer function phase shifts (TF(φ)) were computed as CA measures. Spearman correlations (ρ) and Bland Altman limits of agreement (BAloa) between NIRS- and TCD-derived CA measures were computed. BAloa separation < 50° was considered a high absolute agreement. RESULTS: NIRS- and TCD-derived CA estimates were significantly correlated during supine rest (ρ = 0.22–0.30, N = 111–120) and repeated sit-to-stand transitions (ρ = 0.46–0.61, N = 19–32). BAloa separation ranged between 87° and 112° (supine rest) and 65°–77° (repeated sit to stand transitions). CONCLUSION: Criterion validity of NIRS-derived CA measures allows for comparison between groups but was insufficient for clinical application in individuals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00421-021-04681-w

Dynamics of temporally interleaved percept-choice sequences: interaction via adaptation in shared neural populations

At the onset of visually ambiguous or conflicting stimuli, our visual system quickly ‘chooses’ one of the possible percepts. Interrupted presentation of the same stimuli has revealed that each percept-choice depends strongly on the history of previous choices and the duration of the interruptions. Recent psychophysics and modeling has discovered increasingly rich dynamical structure in such percept-choice sequences, and explained or predicted these patterns in terms of simple neural mechanisms: fast cross-inhibition and slow shunting adaptation that also causes a near-threshold facilitatory effect. However, we still lack a clear understanding of the dynamical interactions between two distinct, temporally interleaved, percept-choice sequences—a type of experiment that probes which feature-level neural network connectivity and dynamics allow the visual system to resolve the vast ambiguity of everyday vision. Here, we fill this gap. We first show that a simple column-structured neural network captures the known phenomenology, and then identify and analyze the crucial underlying mechanism via two stages of model-reduction: A 6-population reduction shows how temporally well-separated sequences become coupled via adaptation in neurons that are shared between the populations driven by either of the two sequences. The essential dynamics can then be reduced further, to a set of iterated adaptation-maps. This enables detailed analysis, resulting in the prediction of phase-diagrams of possible sequence-pair patterns and their response to perturbations. These predictions invite a variety of future experiments

The actinobacterial transcription factor RbpA binds to the principal sigma subunit of RNA polymerase

RbpA is a small non-DNA-binding transcription factor that associates with RNA polymerase holoenzyme and stimulates transcription in actinobacteria, including Streptomyces coelicolor and Mycobacterium tuberculosis. RbpA seems to show specificity for the vegetative form of RNA polymerase as opposed to alternative forms of the enzyme. Here, we explain the basis of this specificity by showing that RbpA binds directly to the principal σ subunit in these organisms, but not to more diverged alternative σ factors. Nuclear magnetic resonance spectroscopy revealed that, although differing in their requirement for structural zinc, the RbpA orthologues from S. coelicolor and M. tuberculosis share a common structural core domain, with extensive, apparently disordered, N- and C-terminal regions. The RbpA-σ interaction is mediated by the C-terminal region of RbpA and σ domain 2, and S. coelicolor RbpA mutants that are defective in binding σ are unable to stimulate transcription in vitro and are inactive in vivo. Given that RbpA is essential in M. tuberculosis and critical for growth in S. coelicolor, these data support a model in which RbpA plays a key role in the σ cycle in actinobacteria

Retinotopic Mapping of Categorical and Coordinate Spatial Relation Processing in Early Visual Cortex

Spatial relations are commonly divided in two global classes. Categorical relations concern abstract relations which define areas of spatial equivalence, whereas coordinate relations are metric and concern exact distances. Categorical and coordinate relation processing are thought to rely on at least partially separate neurocognitive mechanisms, as reflected by differential lateralization patterns, in particular in the parietal cortex. In this study we address this textbook principle from a new angle. We studied retinotopic activation in early visual cortex, as a reflection of attentional distribution, in a spatial working memory task with either a categorical or a coordinate instruction. Participants were asked to memorize a dot position, with regard to a central cross, and to indicate whether a subsequent dot position matched the first dot position, either categorically (opposite quadrant of the cross) or coordinately (same distance to the centre of the cross). BOLD responses across the retinotopic maps of V1, V2, and V3 indicate that the spatial distribution of cortical activity was different for categorical and coordinate instructions throughout the retention interval; a more local focus was found during categorical processing, whereas focus was more global for coordinate processing. This effect was strongest for V3, approached significance in V2 and was absent in V1. Furthermore, during stimulus presentation the two instructions led to different levels of activation in V3 during stimulus encoding; a stronger increase in activity was found for categorical processing. Together this is the first demonstration that instructions for specific types of spatial relations may yield distinct attentional patterns which are already reflected in activity early in the visual cortex

Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal lymphoma subtype. This retrospective study elucidates the currently unknown genetic background of a large clinically well-annotated cohort of DLBCL with osseous localizations (O-DLBCL), including PB-DLBCL. A total of 103 patients with O-DLBCL were included and compared with 63 (extra)nodal non-osseous (NO)-DLBCLs with germinal center B-cell phenotype (NO-DLBCL-GCB). Cell-of-origin was determined by immunohistochemistry and gene-expression profiling (GEP) using (extended)-NanoString/Lymph2Cx analysis. Mutational profiles were identified with targeted next-generation deep sequencing, including 52 B-cell lymphoma-relevant genes. O-DLBCLs, including 34 PB-DLBCLs, were predominantly classified as GCB phenotype based on immunohistochemistry (74%) and NanoString analysis (88%). Unsupervised hierarchical clustering of an extended-NanoString/Lymph2Cx revealed significantly different GEP clusters for PB-DLBCL as opposed to NO-DLBCL-GCB (P < .001). Expression levels of 23 genes of 2 different targeted GEP panels indicated a centrocyte-like phenotype for PB-DLBCL, whereas NO-DLBCL-GCB exhibited a centroblast-like constitution. PB-DLBCL had significantly more frequent mutations in four GCB-associated genes (ie, B2M, EZH2, IRF8, TNFRSF14) compared with NO-DLBCL-GCB (P = .031, P = .010, P = .047, and P = .003, respectively). PB-DLBCL, with its corresponding specific mutational profile, was significantly associated with a superior survival compared with equivalent Ann Arbor limited-stage I/II NO-DLBCL-GCB (P = .016). This study is the first to show that PB-DLBCL is characterized by a GCB phenotype, with a centrocyte-like GEP pattern and a GCB-associated mutational profile (both involved in immune surveillance) and a favorable prognosis. These novel biology-associated features provide evidence that PB-DLBCL represents a distinct extranodal DLBCL entity, and its specific mutational landscape offers potential for targeted therapies (eg, EZH2 inhibitors)

Correction:How the COVID-19 pandemic highlights the necessity of animal research (vol 30, pg R1014, 2020)

(Current Biology 30, R1014–R1018; September 21, 2020) As a result of an author oversight in the originally published version of this article, a number of errors were introduced in the author list and affiliations. First, the middle initials were omitted from the names of several authors. Second, the surname of Dr. van Dam was mistakenly written as “Dam.” Third, the first name of author Bernhard Englitz was misspelled as “Bernard” and the surname of author B.J.A. Pollux was misspelled as “Pullox.” Finally, Dr. Keijer's first name was abbreviated rather than written in full. These errors, as well as various errors in the author affiliations, have now been corrected online

Crossmodal duration perception involves perceptual grouping, temporal ventriloquism, and variable internal clock rates

Here, we investigate how audiovisual context affects perceived event duration with experiments in which observers reported which of two stimuli they perceived as longer. Target events were visual and/or auditory and could be accompanied by nontargets in the other modality. Our results demonstrate that the temporal information conveyed by irrelevant sounds is automatically used when the brain estimates visual durations but that irrelevant visual information does not affect perceived auditory duration (Experiment 1). We further show that auditory influences on subjective visual durations occur only when the temporal characteristics of the stimuli promote perceptual grouping (Experiments 1 and 2). Placed in the context of scalar expectancy theory of time perception, our third and fourth experiments have the implication that audiovisual context can lead both to changes in the rate of an internal clock and to temporal ventriloquism-like effects on perceived on- and offsets. Finally, intramodal grouping of auditory stimuli diminished any crossmodal effects, suggesting a strong preference for intramodal over crossmodal perceptual grouping (Experiment 5)