Phase-Dependent Interactions in Visual Cortex to Combinations of First- and Second-Order Stimuli.

A fundamental task of the visual system is to extract figure-ground boundaries between objects, which are often defined, not only by differences in luminance, but also by "second-order" contrast or texture differences. Responses of cortical neurons to both first- and second-order patterns have been studied extensively, but only for responses to either type of stimulus in isolation. Here, we examined responses of visual cortex neurons to the spatial relationship between superimposed periodic luminance modulation (LM) and contrast modulation (CM) stimuli, the contrasts of which were adjusted to give equated responses when presented alone. Extracellular single-unit recordings were made in area 18 of the cat, the neurons of which show responses to CM and LM stimuli very similar to those in primate area V2 (Li et al., 2014). Most neurons showed a significant dependence on the relative phase of the combined LM and CM patterns, with a clear overall optimal response when they were approximately phase aligned. The degree of this phase preference, and the contributions of suppressive and/or facilitatory interactions, varied considerably from one neuron to another. Such phase-dependent and phase-invariant responses were evident in both simple- and complex-type cells. These results place important constraints on any future model of the underlying neural circuitry for second-order responses. The diversity in the degree of phase dependence between LM and CM stimuli that we observed could help to disambiguate different kinds of boundaries in natural scenes. SIGNIFICANCE STATEMENT: Many visual cortex neurons exhibit orientation-selective responses to boundaries defined by differences either in luminance or in texture contrast. Previous studies have examined responses to either type of boundary in isolation, but here we measured systematically responses of cortical neurons to the spatial relationship between superimposed periodic luminance-modulated (LM) and contrast-modulated (CM) stimuli with contrasts adjusted to give equated responses. We demonstrate that neuronal responses to these compound stimuli are highly dependent on the relative phase between the LM and CM components. Diversity in the degree of such phase dependence could help to disambiguate different kinds of boundaries in natural scenes, for example, those arising from surface reflectance changes or from illumination gradients such as shading or shadows

Visual Dysfunction in Huntington's Disease: A Systematic Review.

It is well-documented that patients with Huntington's disease (HD) exhibit specific deficits in visual cognition. A less well-documented literature also exists that suggests people with HD experience a number of disease-related changes to more rudimentary sensory visual processing. Here, we review evidence for the effects of HD on the integrity of the early visual pathways in humans along with changes to low-level visual sensitivity. We find evidence for reduced structural and functional integrity of the visual pathways, marked by retinal thinning, reduced VEP amplitude, and cell loss and thinning in visual cortex. We also find evidence of visual perceptual deficits, particularly for colour and motion. We suggest that future studies with well-defined HD and HD-related groups in appropriate numbers that systematically examine the relationship between structural changes to the visual system, basic visual perceptual deficits and disease stage/severity are therefore likely to yield promising results

Quality of life of Syrian refugees living in camps in the Kurdistan Region of Iraq

The current study explores the perceived quality of life of Syrian refugees who have entered the Kurdistan Region of Iraq. Two hundred and seventy participants residing in refugee camps in the Erbil region in Kurdistan completed the WHOQOL-BREF, which measures Quality of Life (QOL) within four domains; physical, psychological, social relationships and environment. Syrian refugees in Kurdistan scored significantly lower for general population norms on physical health, psychological and environment QOL, and score significantly lower for physical health and psychological QOL for refugees in the Gaza strip. However, respondents in the current sample scored significantly higher on environment QOL compared to refugees in the Gaza strip, and significantly higher on all the QOL domains than those reported for refugees inWest Africa. Finally, Syrian refugees in Kurdistan scored significantly higher than general population norms for social relationships QOL. The current findings provide the first report of QOL domain scores among Syrian refugees in the Kurdistan camps and suggest that social relationships and environmental QOL circumstances are relatively satisfactory, and that further investigation might be focused on physical and psychological QOL

The ups and downs of global motion perception : a paradoxical advantage for smaller stimuli in the aging visual system

Recent evidence suggests that normal aging is typically accompanied by impairment in the ability to perceive the global (overall) motion of visual objects in the world. The purpose of this study was to examine the interplay between age-related changes in the ability to perceive translational global motion (up vs. down) and important factors such as the spatial extent (size) over which movement occurs and how cluttered the moving elements are (density). We used random dot kinematograms (RDKs) and measured motion coherence thresholds (% signal elements required to reliably discriminate global direction) for young and older adults. We did so as a function of the number and density of local signal elements, and the aperture area in which they were displayed. We found that older adults' performance was relatively unaffected by changes in aperture size, the number and density of local elements in the display. In young adults, performance was also insensitive to element number and density but was modulated markedly by display size, such that motion coherence thresholds decreased as aperture area increased (participants required fewer local elements to move coherently to determine the overall image direction). With the smallest apertures tested, young participants' motion coherence thresholds were considerably higher (~1.5 times worse) than those of their older counterparts. Therefore, when RDK size is relatively small, older participants were actually better than young participants at processing global motion. These findings suggest that the normal (disease-free) aging process does not lead to a general decline in perceptual ability and in some cases may be visually advantageous. The results have important implications for the understanding of the consequences of aging on visual function and a number of potential explanations are explored. These include age-related changes in spatial summation, reduced cortical inhibition, neural blur and attentional resource allocation

Increased Vulnerability to Pattern-Related Visual Stress in Myalgic Encephalomyelitis

The objective of this study was to determine vulnerability to pattern-related visual stress in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A total of 20 ME/CFS patients and 20 matched (age, gender) controls were recruited to the study. Pattern-related visual stress was determined using the Pattern Glare Test. Participants viewed three patterns, the spatial frequencies (SF) of which were 0.3 (low-SF), 2.3 (mid-SF), and 9.4 (high-SF) cycles per degree (c/deg). They reported the number of distortions they experienced when viewing each pattern. ME/CFS patients exhibited significantly higher pattern glare scores than controls for the mid-SF pattern. Mid-high SF differences were also significantly higher in patients than controls. These findings provide evidence of altered visual perception in ME/CFS. Pattern-related visual stress may represent an identifiable clinical feature of ME/CFS that will prove useful in its diagnosis. However, further research is required to establish if these symptoms reflect ME/CFS-related changes in the functioning of sensory neural pathways

Dissociation of place preference and tolerance responses to sucrose using a dopamine antagonist in the planarian.

In rodents, sucrose has been found to elicit addictive-like behaviours like the development of tolerance and the association with cues present at the time of consumption. Furthermore, the neurochemical response to sucrose binges is equivalent to the one observed in response to the abuse of addictive substances like cocaine. The experiments reported here address the effects of sucrose on an invertebrate model, the Platyhelminth brown planarian. The animals exposed to a 10% sucrose solution in one context developed a conditioned place preference (CPP) which was subsequently extinguished in the absence of the rewarding agent. However, one exposure to sucrose per se sufficed to reinstate the CPP response, suggesting sucrose-induced CPP can be characterised as a standard Pavlovian response. The same training procedure led to the development of context-specific tolerance to the effects of sucrose. However, comparing animals treated with dopamine D1 antagonist (SCH-23390) with control animals showed that the establishment of CPP, but not the development of tolerance, is mediated by the dopamine reward system

Visual Aspects of Reading Performance in Myalgic Encephalomyelitis (ME)

People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) report vision-related reading difficulty, although this has not been demonstrated objectively. Accordingly, we assessed reading speed and acuity, including crowded acuity and acuity for isolated words using standardized tests of reading and vision, in 27 ME/CFS patients and matched controls. We found that the ME/CFS group exhibited slower maximum reading speed, and had poorer crowded acuity than controls. Moreover, crowded acuity was significantly associated with maximum reading speed, indicating that patients who were more susceptible to visual crowding read more slowly. These findings suggest vision-related reading difficulty belongs to a class of measureable symptoms for ME/CFS patients

Aging effects in cueing tasks as assessed by the ideal observer: peripheral cues.

Previous aging and cueing studies suggest that automatic orienting driven by peripheral cues is preserved with aging; however, inconsistencies can be found. One issue might be the use of response times (RT) to assess cueing effects (invalid RT--valid RT), which, in many cases, may not have clear quantitative predictions. We propose an ideal observer (IO) analysis of accuracy estimating participants' internal value of cue validity, or weight, which should equal the actual cue validity. The weight measures the use of information provided by the cue and is insensitive to variations in set size and difficulty, thus potentially providing advantages to RT. Older (n = 54) and younger (n = 58) participants performed a yes/no detection task of a two-dimensional (2-D) Gaussian (60 ms). Square peripheral precues (150 ms) indicated likely target locations (70% valid) across two or six locations (set sizes). For cueing effects, (valid--invalid hit rates), younger participants had set-size effects (larger cueing effects for set size 6), while older participants did not. The opposite pattern was found for weights (younger: no set-size effects, older: set-size effects) due to the IO predicting larger cueing effects for larger set sizes. Comparisons to the ideal weight (cue validity) suggested that older participants used the cue information effectively with set size 2 (as or more so than younger participants), but not with set size 6. These results suggest that attentional deficits from aging in peripheral cueing tasks may only arise as difficulty increases, such as larger set sizes

Action video game training reduces the Simon Effect.

A number of studies have shown that training on action video games improves various aspects of visual cognition including selective attention and inhibitory control. Here, we demonstrate that action video game play can also reduce the Simon Effect, and, hence, may have the potential to improve response selection during the planning and execution of goal-directed action. Non-game-players were randomly assigned to one of four groups; two trained on a first-person-shooter game (Call of Duty) on either Microsoft Xbox or Nintendo DS, one trained on a visual training game for Nintendo DS, and a control group who received no training. Response times were used to contrast performance before and after training on a behavioral assay designed to manipulate stimulus-response compatibility (the Simon Task). The results revealed significantly faster response times and a reduced cost of stimulus-response incompatibility in the groups trained on the first-person-shooter game. No benefit of training was observed in the control group or the group trained on the visual training game. These findings are consistent with previous evidence that action game play elicits plastic changes in the neural circuits that serve attentional control, and suggest training may facilitate goal-directed action by improving players' ability to resolve conflict during response selection and execution

A phase I clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies.

We report the results of a multi-center Phase I dose escalation study of the selective BTK inhibitor ONO/GS-4059 in 90 patients with relapsed/refractory B-cell malignancies. There were 9 dose escalation cohorts ranging from 20mg once daily (OD) to 600mg OD with twice daily (BID) regimens of 240mg and 300mg BID also investigated. 24/25 (96%) evaluable chronic lymphocytic leukemia (CLL) patients responded to ONO/GS-4059, with a median treatment duration of 80 weeks; 21 CLL patients remain on treatment. Lymph node responses were rapid and associated with a concurrent lymphocytosis in most patients. 11/12 (92%) evaluable patients with Mantle Cell Lymphoma (MCL) responded and 8 remain on study (median treatment duration, 40 weeks). 11/31 (35%) non-germinal center B-cell diffuse large B-cell lymphoma (DLBCL) patients responded but median treatment duration was 12 weeks due to development of progressive disease. ONO/GS-4059 was very well tolerated with 75% of adverse events being CTC-AE V4.0 Grade 1 or Grade 2. Grade 3/4 adverse events were mainly hematological and recovered spontaneously during ongoing therapy. One CLL patient experienced a Grade 3 treatment-related bleeding event (spontaneous muscle hematoma) but no clinically significant diarrhea, cardiac dysrhythmias or arthralgia were observed. No maximal tolerated dose (MTD) was reached in the CLL cohort. In the NHL cohort, 4 patients developed a DLT at higher doses, yielding an MTD of 480mg OD. ONO/GS-4059 has significant activity in relapsed/refractory B-cell malignancies without major drug-related toxicity. The selectivity of ONO/GS-4059 should confer advantages in combination therapies. This clinical trial is registered to www.clinicaltrials.gov as NCT01659255