Spatial summation for motion detection.

We used the psychophysical summation paradigm to reveal some spatial characteristics of the mechanism responsible for detecting a motion-defined visual target in central vision. There has been much previous work on spatial summation for motion detection and direction discrimination, but none has assessed it in terms of the velocity threshold or used velocity noise to provide a measure of the efficiency of the velocity processing mechanism. Motion-defined targets were centered within square fields of randomly selected gray levels. The motion was produced within the disk-shaped target region by shifting the pixels rightwards for 0.2 s. The uniform target motion was perturbed by Gaussian motion noise in horizontal strips of 16 pixels. Independent variables were field size, the diameter of the disk target, and the variance of an independent perturbation added to the (signed) velocity of each 16-pixel strip. The dependent variable was the threshold velocity for target detection. Velocity thresholds formed swoosh-shaped (descending, then ascending) functions of target diameter. Minimum values were obtained when targets subtended approximately 2 degrees of visual angle. The data were fit with a continuum of models, extending from the theoretically ideal observer through various inefficient and noisy refinements thereof. In particular, we introduce the concept of sparse sampling to account for the relative inefficiency of the velocity thresholds. The best fits were obtained from a model observer whose responses were determined by comparing the velocity profile of each stimulus with a limited set of sparsely sampled "DoG" templates, each of which is the product of a random binary array and the difference between two 2-D Gaussian density functions.

Success rates, near-response patterns, and learning trends with free-fusion stereograms.

Free-fusion stereograms are routinely used for demonstrating various stereoscopic effects. Yet, untrained observers find it challenging to perform this task. This study showed that only less than 1/3rd of sixty-one pre-presbyopic adults with normal binocular vision could successfully free-fuse random-dot image pairs and identify the stereoscopic shapes embedded in these patterns. Another one-third of participants performed the task with poor success rates, while the remaining could not perform the task. There was a clear dissociation of vergence and accommodative responses in participants who were successful with free-fusion, as recorded using a dynamic infrared eye tracker and photorefractor. Those in the unsuccessful cluster either showed strong vergence and accommodation or weak vergence and strong accommodation during the task. These response patterns, however, were specific to the free-fusion task because all these participants generated good convergence/accommodation to real-world targets and to conflicting vergence and accommodative demands stimulated with prisms or lenses. Task performance of the unsuccessful cluster also improved significantly following pharmacological paralysis of accommodation and reached the performance levels of the successful cluster. A minority of participants also appeared to progressively learn to dissociate one of the two directions of their vergence and accommodation crosslinks with repeated free-fusion trials. These results suggest that successful free-fusion might depend upon how well participants generate a combination of volitional and reflex vergence responses to large differences in disparity with conflicting static accommodative demands. Such responses would require that only one direction of the vergence-accommodation crosslinks be active at any given time. The sequence of near-responses could also be learnt through repeated trials to optimize task performance.

Cannabidiol as an Adjunct to Botulinum Toxin in Blepharospasm - A Randomized Pilot Study.

Purpose: The purpose of this study was to evaluate the safety and efficacy of low dose cannabidiol (CBD; Epidiolex) as adjunctive therapy for idiopathic adult-onset blepharospasm (BPS), as well as develop a novel objective assessment methodology to gauge response. Methods: Prospective, randomized, double-masked, placebo-controlled crossover design of 6 months duration of 12 patients with BPS undergoing routine maximal botulinum toxin (BTX) therapy and experiencing breakthrough symptoms. Participants received their standard BTX every 3 months and were randomized to group A = CBD daily in cycle 1, followed by placebo in cycle 2 or group B = placebo followed by CBD. Videos recorded at days 0, 45, and 90 of each cycle were analyzed to quantify eyelid kinematics. The Jankovic Rating Scale (JRS) was used to provide a clinical rating. Results: All 12 patients completed the study without adverse events. CBD decreased median eyelid closure amplitude by 19.1% (-1.66 mm, confidence interval [CI] = -3.19 to -0.14 mm, P = 0.03), decreased median eyelid closure duration by 15.8% (-18.35 ms, CI = -29.37 to -7.32 ms, P = 0.001), and increased the maximum eyelid closure velocity by 34.8% (-13.26 mm/ms, CI = -20.93 to -5.58 mm/ms, P = 0.001). The JRS showed a 0.5 reduction in severity and frequency, which was not statistically significant. Conclusions: Low dose CBD was safely tolerated and improved several BPS kinematic parameters. The clinical scale suggested a direction of effect but may have been underpowered. Further studies are needed to better quantify the clinical relevance. Translational Relevance: This work describes a novel assessment methodology and therapeutic approach to bBPS.

Suprathreshold length summation.

To investigate the mechanisms underlying elongated spatial summation with a pattern-masking paradigm, we measured the contrast detection thresholds for elongated Gabor targets situated at 3° eccentricity to either the left or right of the fixation and elongated along an arc of the same radius to access homogeneous retinal sensitivity. The mask was a ring with a Gabor envelope of the same 3° center radius containing either a concentric (iso-orientation mask) or a radial (orthogonal mask) modulation. The task of the observer was to indicate whether the target in each trial was on the left or the right of the fixation. With orthogonal or low contrast iso-orientation masks, target thresholds first decreased with size with slope -1 on log-log coordinates until the target length reached 45' (specified as the half-height full-width of the Gabor envelope) and then further decreased according to a slope of -1/2, the latter being the signature of an ideal summation process. When the contrast of the iso-orientation mask was sufficiently high, however, the target thresholds, while still showing a -1 slope up to ∼10', asymptoted up to about 50' length, suggesting that the presence of the mask eliminated the ideal summation regime. Beyond about 50', the data approximated another -1 slope decrease in threshold, suggesting the existence of an extra-long channel that is not revealed by the conventional spatial summation paradigm. The full results could be explained by a divisive inhibition model, in which second-order filters sum responses across local oriented channels, combined with a single extra-long filter at least 300' in extent. In this model, the local filter response is given by the linear excitation of the local channels raised to a power, and scaled by divisive inhibition from all channels in the neighborhood. With the high-contrast iso-orientation masks, such divisive inhibition swamps the response to eliminate the ideal summation regime until the stimulus is long enough to activate the extra-long filter.

Spatial cognition training rapidly induces cortical plasticity in blind navigation: Transfer of training effect & Granger causal connectivity analysis.

How is the cortical navigation network reorganized by the Likova Cognitive-Kinesthetic Navigation Training? We measured Granger-causal connectivity of the frontal-hippocampal-insular-retrosplenial-V1 network of cortical areas before and after this one-week training in the blind. Primarily top-down influences were seen during two tasks of drawing-from-memory (drawing complex maps and drawing the shortest path between designated map locations), with the dominant role being congruent influences from the egocentric insular to the allocentric spatial retrosplenial cortex and the amodal-spatial sketchpad of V1, with concomitant influences of the frontal cortex on these areas. After training, and during planning-from-memory of the best on-demand path, the hippocampus played a much stronger role, with the V1 sketchpad feeding information forward to the retrosplenial region. The inverse causal influences among these regions generally followed a recursive feedback model of the opposite pattern to a subset of congruent influences. Thus, this navigational network reorganized its pattern of causal influences with task demands and the navigation training, which produced marked enhancement of the navigational skills.

Voluntary torque production is unaffected by changes in local thermal sensation during normothermia and hyperthermia.

NEW FINDINGS: What is the central question of this study? Hyperthermia reduces the human capacity to produce muscular force, which is associated with decreased neural drive: does mitigating a reduction in neural drive by altering localised thermal sensation help to preserve voluntary force output? What is the main finding and its importance? Altering thermal sensation by cooling and heating the head independent of core temperature did not change neural drive or benefit voluntary force production. Head cooling did slow the rate of rise in core temperature during heating, which may have practical applications in passive settings. ABSTRACT: This study investigated altered local head and neck thermal sensation on maximal and rapid torque production during voluntary contractions. Nine participants completed four visits in two environmental conditions: at rectal temperatures ∼39.5°C in hot (HOT; ∼50°C, ∼39% relative humidity) and ∼37°C in thermoneutral (NEU; ∼22°C, ∼46% relative humidity) conditions. Local thermal sensation was manipulated by heating in thermoneutral conditions and cooling in hot conditions. Evoked twitches and octets were delivered at rest. Maximum voluntary torque (MVT), normalised surface electromyography (EMG) and voluntary activation (VA) were assessed during brief maximal isometric voluntary contractions of the knee extensors. Rate of torque development (RTD) and EMG were measured during rapid voluntary contractions. MVT (P = 0.463) and RTD (P = 0.061) were similar between environmental conditions despite reduced VA (-6%; P = 0.047) and EMG at MVT (-31%; P = 0.019). EMG in the rapid voluntary contractions was also lower in HOT versus NEU during the initial 100 ms (-24%; P = 0.035) and 150 ms (-26%; P = 0.035). Evoked twitch (+70%; P < 0.001) and octet (+27%; P < 0.001) RTD during the initial 50 ms were greater in the HOT compared to NEU conditions, in addition to a faster relaxation rate of the muscle (-33%; P < 0.001). In conclusion, hyperthermia reduced neural drive without affecting voluntary torque, likely due to the compensatory effects of improved intrinsic contractile function and faster contraction and relaxation rates of the knee extensors. Changes in local thermal perception of the head and neck whilst hyperthermic or normothermic did not affect voluntary torque.

Heat acclimation reduces the effects of whole-body hyperthermia on knee-extensor relaxation rate, but does not affect voluntary torque production.

PURPOSE: This study investigated the effects of acute hyperthermia and heat acclimation (HA) on maximal and rapid voluntary torque production, and their neuromuscular determinants. METHODS: Ten participants completed 10 days of isothermic HA (50 °C, 50% rh) and had their knee-extensor neuromuscular function assessed in normothermic and hyperthermic conditions, pre-, after 5 and after 10 days of HA. Electrically evoked twitch and octet (300 Hz) contractions were delivered at rest. Maximum voluntary torque (MVT), surface electromyography (EMG) normalised to maximal M-wave, and voluntary activation (VA) were assessed during brief maximal isometric voluntary contractions. Rate of torque development (RTD) and normalised EMG were measured during rapid voluntary contractions. RESULTS: Acute hyperthermia reduced neural drive (EMG at MVT and during rapid voluntary contractions; P < 0.05), increased evoked torques (P < 0.05), and shortened contraction and relaxation rates (P < 0.05). HA lowered resting rectal temperature and heart rate after 10 days (P < 0.05), and increased sweating rate after 5 and 10 days (P < 0.05), no differences were observed between 5 and 10 days. The hyperthermia-induced reduction in twitch half-relaxation was attenuated after 5 and 10 days of HA, but there were no other effects on neuromuscular function either in normothermic or hyperthermic conditions. CONCLUSION: HA-induced favourable adaptations to the heat after 5 and 10 days of exposure, but there was no measurable benefit on voluntary neuromuscular function in normothermic or hyperthermic conditions. HA did reduce the hyperthermic-induced reduction in twitch half-relaxation time, which may benefit twitch force summation and thus help preserve voluntary torque in hot environmental conditions.

The effects of combined action observation and motor imagery on corticospinal excitability and movement outcomes: Two meta-analyses.

Motor simulation interventions involving motor imagery (MI) and action observation (AO) have received considerable interest in the behavioral sciences. A growing body of research has focused on using AO and MI simultaneously, termed 'combined action observation and motor imagery' (AOMI). The current paper includes two meta-analyses that quantify changes in corticospinal excitability and motor skill performance for AOMI compared to AO, MI and control conditions. Specifically, the first meta-analysis collated and synthesized existing motor evoked potential (MEP) amplitude data from transcranial magnetic stimulation studies and the second meta-analysis collated and synthesized existing movement outcome data from behavioral studies. AOMI had a positive effect compared to control and AO but not MI conditions for both MEP amplitudes and movement outcomes. No methodological factors moderated the effects of AOMI, indicating a robust effect of AOMI across the two outcome variables. The results of the meta-analyses are discussed in relation to existing literature on motor simulation and skill acquisition, before providing viable directions for future research on this topic.

Correction: Cold-Induced Vasodilation during Single Digit Immersion in 0°C and 8°C Water in Men and Women.

[This corrects the article DOI: 10.1371/journal.pone.0122592.].

Reduced Expression of TMEM16A Impairs Nitric Oxide-Dependent Cl- Transport in Retinal Amacrine Cells.

Postsynaptic cytosolic Cl- concentration determines whether GABAergic and glycinergic synapses are inhibitory or excitatory. We have shown that nitric oxide (NO) initiates the release of Cl- from acidic internal stores into the cytosol of retinal amacrine cells (ACs) thereby elevating cytosolic Cl-. In addition, we found that cystic fibrosis transmembrane conductance regulator (CFTR) expression and Ca2+ elevations are necessary for the transient effects of NO on cytosolic Cl- levels, but the mechanism remains to be elucidated. Here, we investigated the involvement of TMEM16A as a possible link between Ca2+ elevations and cytosolic Cl- release. TMEM16A is a Ca2+-activated Cl- channel that is functionally coupled with CFTR in epithelia. Both proteins are also expressed in neurons. Based on this and its Ca2+ dependence, we test the hypothesis that TMEM16A participates in the NO-dependent elevation in cytosolic Cl- in ACs. Chick retina ACs express TMEM16A as shown by Western blot analysis, single-cell PCR, and immunocytochemistry. Electrophysiology experiments demonstrate that TMEM16A functions in amacrine cells. Pharmacological inhibition of TMEM16A with T16inh-AO1 reduces the NO-dependent Cl- release as indicated by the diminished shift in the reversal potential of GABAA receptor-mediated currents. We confirmed the involvement of TMEM16A in the NO-dependent Cl- release using CRISPR/Cas9 knockdown of TMEM16A. Two different modalities targeting the gene for TMEM16A (ANO1) were tested in retinal amacrine cells: an all-in-one plasmid vector and crRNA/tracrRNA/Cas9 ribonucleoprotein. The all-in-one CRISPR/Cas9 modality did not change the expression of TMEM16A protein and produced no change in the response to NO. However, TMEM16A-specific crRNA/tracrRNA/Cas9 ribonucleoprotein effectively reduces both TMEM16A protein levels and the NO-dependent shift in the reversal potential of GABA-gated currents. These results show that TMEM16A plays a role in the NO-dependent Cl- release from retinal ACs.

The Nature of Illusions: A New Synthesis Based on Verifiability.

This overview discusses the nature of perceptual illusions with particular reference to the theory that illusions represent the operation of a sensory code for which there is no meaningful ground truth against which the illusory percepts can be compared, and therefore there are no illusions as such. This view corresponds to the Bayesian theory that "illusions" reflect unusual aspects of the core strategies of adapting to the natural world, again implying that illusions are simply an information processing characteristic. Instead, it is argued that a more meaningful approach to the field that we call illusions is the Ebbinghaus approach of comparing the illusory percept with a ground truth that is directly verifiable as aberrant by the observer in the domain of the illusory phenomenology (as opposed to relying on the authority of other experts). This concept of direct verifiability not only provides an operational definition of "illusion"; it also makes their interactive observation more effective and informative as to the perceptual processes underlying the illusory appearance. An expanded version of Gregory's categorization of types of illusion is developed, and a range of classic and more recent illusions that illustrate the differences between these philosophical viewpoints is considered in detail. Such cases make it clear that the discrepancies from the measurable image structure cannot be simply regarded as idiosyncrasies of sensory coding, but are categorical exemplars of perceptual illusions. The widespread existence of such illusory percepts is indicative of the evolutionary limits of adaptive sensory coding.

Multi-level control of adaptive camouflage by European cuttlefish.

To camouflage themselves on the seafloor, European cuttlefish Sepia officinalis control the expression of about 30 pattern components to produce a range of body patterns.1 If each component were under independent control, cuttlefish could produce at least 230 patterns. To examine how cuttlefish deploy this vast potential, we recorded cuttlefish on seven experimental backgrounds, each designed to resemble a pattern component, and then compared their responses to predictions of two models of sensory control of component expression. The body pattern model proposes that cuttlefish integrate low-level sensory cues to categorize the background and co-ordinate component expression to produce a small number of overall body patterns.2-4 The feature matching model proposes that each component is expressed in response to one (or more) local visual features, and the overall pattern depends upon the combination of features in the background. Consistent with the feature matching model, six of the backgrounds elicited a specific set of one to four components, whereas the seventh elicited eleven components typical of a disruptive body pattern. This evidence suggests that both modes of control are important, and we suggest how they can be implemented by a recent hierarchical model of the cuttlefish motor system.5,6.

Brain trauma impacts retinal processing: photoreceptor pathway interactions in traumatic light sensitivity.

BACKGROUND: Concussion-induced light sensitivity, or traumatic photalgia, is a lifelong debilitating problem for upwards of 50% of mild traumatic brain injury (mTBI) cases, though of unknown etiology. We employed spectral analysis of electroretinographic (ERG) responses to assess retinal changes in mTBI as a function of the degree of photalgia. METHODS: The design was a case-control study of the changes in the ERG waveform as a function of level of light sensitivity in individuals who had suffered incidents of mild traumatic brain injury. The mTBI participants were categorized into non-, mild-, and severe-photalgic groups based on their spectral nociophysical settings. Light-adapted ERG responses were recorded from each eye for 200 ms on-off stimulation of three spectral colors (R:red, G:green, and B:blue) and their sum (W:white) at the highest pain-free intensity level for each participant. The requirement of controls for testing hypersensitive individuals at lower light levels was addressed by recording a full light intensity series in the control group. RESULTS: Both the b-wave and the photopic negative response (PhNR) were significantly reduced in the non-photalgic mTBI group relative to controls. In the photalgic groups, the main b-wave peak shifted to the timing of the rod b-wave, with reduced amplitude at the timing of the cone response. CONCLUSION: These results suggest the interpretation that the primary etiology of the painful light sensitivity in mTBI is release of the rod pathway from cone-mediated inhibition at high light levels, causing overactivation of the rod pathway.

The Influence of a Competitive Field Hockey Match on Cognitive Function.

Despite the known positive effects of acute exercise on cognition, the effects of a competitive team sport match are unknown. In a randomized crossover design, 20 female and 17 male field hockey players (19.7 ± 1.2 years) completed a battery of cognitive tests (Visual Search, Stroop, Corsi Blocks, and Rapid Visual Information Processing) prior to, at half-time, and immediately following a competitive match (or control trial of seated rest); with effect sizes (ES) presented as raw ES from mixed effect models. Blood samples were collected prior to and following the match and control trial, and analyzed for adrenaline, noradrenaline, brain derived neurotrophic factor (BDNF), cathepsin B, and cortisol. The match improved response times for a simple perception task at full-time (ES = -14 ms; P < 0.01) and response times on the complex executive function task improved at half-time (ES = -44 ms; P < 0.01). Working memory declined at full-time on the match (ES = -0.6 blocks; P < 0.01). The change in working memory was negatively correlated with increases in cortisol (r = -0.314, P = 0.01; medium), as was the change in simple perception response time and the change in noradrenaline concentration (r = -0.284, P = 0.01; small to medium). This study is the first to highlight the effects a competitive hockey match can have on cognition. These findings have implications for performance optimization, as understanding the influence on specific cognitive domains across a match allows for the investigation into strategies to improve these aspects.

Self-Regulation of Seat of Attention Into Various Attentional Stances Facilitates Access to Cognitive and Emotional Resources: An EEG Study.

This study provides evidence supporting the operation of a novel cognitive process of a somatic seat of attention, or ego-center, whose somatic location is under voluntary control and that provides access to differential emotional resources. Attention has typically been studied in terms of what it is directed toward, but it can also be associated with a localized representation in the body image that is experienced as the source or seat of attention-an aspect that has previously only been studied by subjective techniques. Published studies of this phenomenon under terms such as egocenter or self-location suggest that the seat of attention can be situated in various ways within the experienced body, resulting in what are here referred to as different attentional stances. These studies also provide evidence that changes in attentional stance are associated with differences in cognitive skill, emotional temperament, self-construal, and social and moral attitudes, as well as with access to certain states of consciousness. In the present study, EEG results from multiple trials of each of 11 specific attentional stances confirmed that patterns of neural activity associated with the voluntarily control of attentional stances can be reliably measured, providing evidence for a differential neural substrate underlying the subjective location of the seat of attention. Additionally, brain activation patterns for the attentional stances showed strong correlations with EEG signatures associated with specific positive emotional states and with arousal, confirming that differential locations of the seat of attention can be objectively associated with different emotion states, as implied in previous literature. The ability to directly manage the seat of attention into various attentional stances holds substantial potential for facilitating access to specific cognitive and emotional resources in a new way.

Antibody secreting cells are critically dependent on integrin α4ß7/MAdCAM-1 for intestinal recruitment and control of the microbiota during chronic colitis.

T and B cells employ integrin α4ß7 to migrate to intestine under homeostatic conditions. Whether those cells differentially rely on α4ß7 for homing during inflammatory conditions has not been fully examined. This may have implications for our understanding of the mode of action of anti-integrin therapies in inflammatory bowel disease (IBD). Here, we examined the role of α4ß7 integrin during chronic colitis using IL-10-/- mice, ß7-deficient IL-10-/-, IgA-deficient IL-10-/- mice, and antibody blockade of MAdCAM-1. We found that α4ß7 was predominantly expressed by B cells. ß7 deficiency and MAdCAM-1 blockade specifically depleted antibody secreting cells (ASC) (not T cells) from the colonic LP, leading to a fecal pan-immunoglobulin deficit, severe colitis, and alterations of microbiota composition. Colitis was not due to defective regulation, as dendritic cells (DC), regulatory T cells, retinaldehyde dehydrogenase (RALDH) expression, activity, and regulatory T/B-cell cytokines were all comparable between the strains/treatment. Finally, an IgA deficit closely recapitulated the clinical phenotype and altered microbiota composition of ß7-deficient IL-10-/- mice. Thus, a luminal IgA deficit contributes to accelerated colitis in the ß7-deficient state. Given the critical/nonredundant dependence of IgA ASC on α4ß7:MAdCAM-1 for intestinal homing, B cells may represent unappreciated targets of anti-integrin therapies.

Cartography as Spatial Representation: A new assessment of the competing advantages and drawbacks across fields of science.

The history of cartography has been marked by the endless search for the perfect form for the representation of the information on a spherical surface manifold into the flat planar format of the printed page or computer screen. Dozens of cartographic formats have been proposed over the centuries from ancient Greek times to the present. This is an issue not just for the mapping of the globe, but in all fields of science where spherical entities are found. The perceptual and representational advantages and drawbacks of many of these formats are considered, particularly in the tension between a unified representation, which is always distorted in some dimension, and a minimally distorted representation, which can only be obtained by segmentation into sectorial patches. The use of these same formats for the mapping of spherical manifolds are evaluated, from quantum physics through the mapping of the brain to the large-scale representation of the cosmos.

The Interstitial Pathways as the Substrate of Consciousness: A New Synthesis.

This paper considers three classes of analyses of the nature of consciousness: abstract theories of the functional organization of consciousness, and concrete proposals as to the neural substrate of consciousness, while providing a rationale for contesting non-neural and transcendental conceptualizations of consciousness. It indicates that abstract theories of the dynamic core of consciousness have no force unless they are grounded in the physiology of the brain, since the organization of dynamic systems, such as the Sun, could equally well qualify as conscious under such theories. In reviewing the wealth of studies of human consciousness since the mid-20th century, it concludes that many proposals for the particular neural substrate of consciousness are insufficient in various respects, but that the results can be integrated into a novel scheme that consciousness extends through a subcortical network of interlaminar structures from the brainstem to the claustrum. This interstitial structure has both the specificity and the extended connectivity to account for the array of reportable conscious experiences.

An integrin αEß7-dependent mechanism of IgA transcytosis requires direct plasma cell contact with intestinal epithelium.

Efficient IgA transcytosis is critical for the maintenance of a homeostatic microbiota. In the canonical model, locally-secreted dimeric (d)IgA reaches the polymeric immunoglobulin receptor (pIgR) on intestinal epithelium via simple diffusion. A role for integrin αE(CD103)ß7 during transcytosis has not been described, nor its expression by intestinal B cell lineage cells. We found that αE-deficient (αE-/-) mice have a luminal IgA deficit, despite normal antibody-secreting cells (ASC) recruitment, local IgA production and increased pIgR expression. This deficit was not due to dendritic cell (DC)-derived retinoic acid (RA) nor class-switching defects, as stool from RAG-/- mice reconstituted with αE-/- B cells was also IgA deficient. Flow cytometric, ultrastructural and transcriptional profiling showed that αEß7-expressing ASC represent an undescribed subset of terminally-differentiated intestinal plasma cells (PC) that establishes direct cell to cell contact with intestinal epithelium. We propose that IgA not only reaches pIgR through diffusion, but that αEß7+ PC dock with E-cadherin-expressing intestinal epithelium to directly relay IgA for transcytosis into the intestinal lumen.