Age-related differences in saccadic indices of top-down guidance via short-term memory during visual search.

Aging has been associated with significant declines in the speed and accuracy of visual search. These effects have been attributed partly to low-level (bottom-up) factors including reductions in sensory acuity and general processing speed. Aging is also associated with changes in top-down attentional control, but the impact of these on search is less well-understood. The present study investigated age-related differences in top-down attentional control by comparing the speed and accuracy of saccadic sampling in the presence and absence of top-down information about target color in young (YA) and older (OA) observers. Displays contained an equal number of red and blue Landholt stimuli. Targets were distinguished from distractors by a unique orientation, and observers reported the direction of the target's gap on each trial. Single-target cues signaled the color of the target with 100% validity. Dual-target cues indicated the target could be present in either colored subgroup. The results revealed reliable group differences in the benefits associated with top-down information on single-target cues compared to dual-target cues. On single-target searches, OA made significantly more saccades than YA to stimuli in the uncued color subset. Single-target cues also produced a smaller advantage in the time taken to fixate the target in OA compared to YA. These results support an age-related decline in observers' use of top-down information to restrict sequences of saccades to a task-relevant subset of objects during visual search. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Reduced Vision-Related Quality of Life in Dementia: A Preliminary Report.

BACKGROUND: Despite experimental evidence for concurrent dementia and visual impairment, there are no currently validated vision-related quality of life measures for use in this population. OBJECTIVE: To establish the extent to which individuals with mild to moderate dementia self-report visual impairment and determine the efficacy of established vision-related quality of life measures for use in a dementia population. METHODS: We compared vision-related quality of life in participants with mild-moderate dementia to healthy (dementia-free) older adults using two existing questionnaire measures already validated for use in older adults. These were the Visual Activities Questionnaire (VAQ) and the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25). RESULTS: Responses on both the VAQ and VFQ-25 revealed a significant effect of dementia on self-reported vision-related quality of life. Visual impairment in dementia was identified in the domains of color discrimination, disability glare, light/dark adaption, acuity/spatial vision, depth perception, peripheral vision, visual search, and visual processing speed. Factor analysis of the data suggested that existing vision-related quality of life measures, designed for use in older adult populations, are likely to provide a robust means of assessing vision-related quality of life in older adults with dementia. This is particularly true of the VAQ, for which one latent factor emerged for both dementia and dementia-free samples. CONCLUSION: Using existing measures designed for use in older adult populations, we have shown that people with dementia experience reduced vision-related quality of life.

Comparison of Logarithmic Reading Charts for Visual Assessment in Normally Sighted Participants.

SIGNIFICANCE: Logarithmic reading charts provide standardized measures of reading performance. Here we show that existing charts provide equivalent assessments of visual aspects of reading that are in good agreement with traditional measures of visual acuity and seem uninfluenced by cognitive (linguistic) factors. PURPOSE: The aims of this study were to (1) determine the equivalence of logarithmic charts of sentence and word reading, (2) evaluate the relationship between reading chart performance and more traditional measures of visual assessment, and (3) establish the influence of linguistic factors on reading chart performance. METHODS: In a sample of 82 normally sighted participants, we determined performance on the reading measures (e.g., reading acuity, reading speed, critical print size) of the following logarithmic charts of sentence and word reading: The Colenbrander English Continuous Text Near Vision Card, Radner Reading Chart, Minnesota Reading Acuity Chart, and Smith-Kettlewell Reading Chart. In doing so, we compared performance on reading measures between charts and with performance on more traditional measures of visual assessment (uncrowded and crowded letter acuity, stereoacuity, accommodation) and cognitive measures of word knowledge and ability (Wechsler Adult Intelligence Scale Vocabulary Subtest, National Adult Reading Test). RESULTS: Factor analysis confirmed that performance on the reading measures (reading acuity, reading speed, critical print size) was equivalent across charts. Reading test performance was also related to more traditional measures of vision, the most consistent of which were significant associations between reading acuity and acuity for single-letter optotypes. There were no significant associations between reading chart performance and cognitive measures of word knowledge and ability. CONCLUSIONS: The findings presented here suggest that logarithmic charts composed of sentences and words represent an alternative to traditional letter acuity testing. This is particularly the case for measures of reading acuity.

Selectively reduced contrast sensitivity in high schizotypy.

Deficits in the ability to encode small differences in contrast between adjacent parts of an image (contrast sensitivity) are well documented in schizophrenic patients. In the present study, we sought to determine whether contrast sensitivity deficits reported in schizophrenic patients are also evident in those who exhibit high schizotypy scores in a typical (i.e., non-schizophrenic) population. Using the O-Life Questionnaire, we determined the effects of schizotypy on spatial (0.5, 2 and 8 c/deg) and spatiotemporal (0.5 and 8 c/deg at 0.5 and 8 Hz) contrast sensitivity in 73 young (18-26 years), majority female (n = 68) participants. We found differences in contrast sensitivity that were spatial, spatiotemporal and O-Life subscale specific. Spatial contrast sensitivity was significantly lower in high, compared to low schizotypes at low spatial frequencies (0.5 c/deg) in those who scored highly on the Unusual Experiences and Cognitive Disorganisation O-Life subscales. For moving stimuli, individuals with high scores on the Unusual Experiences subscale exhibited lower spatiotemporal contrast sensitivity for 0.5 and 8 c/deg patterns drifting at 8 Hz. Although the effects reported here were relatively small, this is the first report of reduced contrast sensitivity in schizotypy.

Dual-action CXCR4-targeting liposomes in leukemia: function blocking and drug delivery.

CXC chemokine receptor 4 (CXCR4) is overexpressed by a broad range of hematological disorders, and its interaction with CXC chemokine ligand 12 (CXCL12) is of central importance in the retention and chemoprotection of neoplastic cells in the bone marrow and lymphoid organs. In this article, we describe the biological evaluation of a new CXCR4-targeting and -antagonizing molecule (BAT1) that we designed and show that, when incorporated into a liposomal drug delivery system, it can be used to deliver cancer therapeutics at high levels to chronic lymphocytic leukemia (CLL) cells. CXCR4 targeting and antagonism by BAT1 were demonstrated alone and following its incorporation into liposomes (BAT1-liposomes). Antagonism of BAT1 against the CXCR4/CXCL12 interaction was demonstrated through signaling inhibition and function blocking: BAT1 reduced ERK phosphorylation and cell migration to levels equivalent to those seen in the absence of CXCL12 stimulation (P < .001). Specific uptake of BAT1-liposomes and delivery of a therapeutic cargo to the cell nucleus was seen within 3 hours of incubation and induced significantly more CLL cell death after 24 hours than control liposomes (P = .004). The BAT1 drug-delivery system is modular, versatile, and highly clinically relevant, incorporating elements of proven clinical efficacy. The combined capabilities to block CXCL12-induced migration and intracellular signaling while simultaneously delivering therapeutic cargo mean that the BAT1-liposome drug-delivery system could be a timely and relevant treatment of a range of hematological disorders, particularly because the therapeutic cargo can be tailored to the disease being treated.

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.

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.

Restricted Spatial Windows of Visibility in Myalgic Encephalomyelitis (ME).

Myalgic encephalomyelitis (ME) is a devastating disorder marked by debilitating fatigue. It not well understood and its diagnosis is controversial. It is very important therefore that significant clinical features are investigated. Visual symptoms in ME represent a group of distinct, quantifiable, clinical features that could significantly improve diagnosis and provide insights into underlying pathology. The purpose of the present study was therefore to explore the effect of ME on spatial windows of visibility using the spatial contrast sensitivity function. Contrast sensitivity was determined for stationary luminance-defined sinusoidal gratings spanning a five-octave range of spatial frequencies (0.5 to 16 c/deg) in a group of 19 individuals with ME and a group of 19 matched (age, gender) controls. Compared to controls, the ME group exhibited a restricted spatial window of visibility for encoding stimulus contrast. This was characterised principally by a contrast sensitivity deficit at lower spatial frequencies and a narrower bandwidth. Our findings suggest that contrast sensitivity deficits may represent a visual marker of ME, and be indicative of abnormal visual processing at the level of the retina and in the cortical and subcortical visual 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.

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.

A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies.

We report the results of a multicenter phase 1 dose-escalation study of the selective Bruton tyrosine kinase (BTK) inhibitor ONO/GS-4059 in 90 patients with relapsed/refractory B-cell malignancies. There were 9 dose-escalation cohorts ranging from 20 mg to 600 mg once daily with twice-daily regimens of 240 mg and 300 mg. Twenty-four of 25 evaluable chronic lymphocytic leukemia (CLL) patients (96%) 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. Eleven of 12 evaluable patients with mantle cell lymphoma (92%) responded (median treatment duration, 40 weeks). Eleven of 31 non-germinal center B-cell diffuse large B-cell lymphoma patients (35%) 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 (AEs) being Common Toxicity Criteria for Adverse Events version 4.0 grade 1 or grade 2. Grade 3/4 AEs were mainly hematologic and recovered spontaneously during 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 non-Hodgkin lymphoma cohort, 4 patients developed a dose-limiting toxicity, yielding an MTD of 480 mg once daily. 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 trial was registered at www.clinicaltrials.gov as #NCT01659255.

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.

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.

Persistent conditioned place preference to cocaine and withdrawal hypo-locomotion to mephedrone in the flatworm planaria.

The purpose of the present study was to determine the effects of exposure to cocaine and mephedrone on conditioned place preference (CPP) and locomotion in the flatworm planaria. Planaria were treated with either cocaine or mephedrone at 1 or 10 µM. Planaria were exposed to 15 min of drug in their non-preferred place (either a rough- or smooth-floored petri dish) on alternate days, and were exposed to normal water in their preferred place on the following day. There were 5 days of conditioning to drug. Planaria were then tested for CPP on day 2, 6 and 13 after withdrawal. We found that animals exhibited CPP to cocaine at both 1 and 10 µM, but not to mephedrone. When examining locomotor activity we found that neither cocaine nor mephedrone treatment showed any evidence of evoking increased motility or locomotor sensitisation. Hypo-motility was seen on the first day of conditioning at concentrations of 10 µM for both cocaine and mephedrone, but had disappeared by the last day of conditioning. Examining chronic withdrawal, only 10 µM mephedrone had a significant effect on motility, decreasing locomotion on day 2 of withdrawal. Taken together we have shown that cocaine evoked CPP in planaria. We have also shown withdrawal depressing effects of mephedrone on motility.

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.

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 in West 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.

Oestrogen, ocular function and low-level vision: a review.

Over the past 10 years, a literature has emerged concerning the sex steroid hormone oestrogen and its role in human vision. Herein, we review evidence that oestrogen (oestradiol) levels may significantly affect ocular function and low-level vision, particularly in older females. In doing so, we have examined a number of vision-related disorders including dry eye, cataract, increased intraocular pressure, glaucoma, age-related macular degeneration and Leber's hereditary optic neuropathy. In each case, we have found oestrogen, or lack thereof, to have a role. We have also included discussion of how oestrogen-related pharmacological treatments for menopause and breast cancer can impact the pathology of the eye and a number of psychophysical aspects of vision. Finally, we have reviewed oestrogen's pharmacology and suggest potential mechanisms underlying its beneficial effects, with particular emphasis on anti-apoptotic and vascular effects.

Breaking good: the inexorable rise of BTK inhibitors in the treatment of chronic lymphocytic leukaemia.

Although expressed in several haematological lineages and involved in multiple different signalling pathways, Bruton tyrosine kinase (BTK) plays an indispensible role in B cells in signalling from the B cell receptor (BCR) for antigen. Many B cell malignancies remain dependent on constitutive BCR signalling, making BTK a functional therapeutic target. Several BTK inhibitors (BTKi) with different kinomes and modes of action are being assessed clinically. This review documents the efficacy and toxicity of BTKi in chronic lymphocytic leukaemia (CLL). Clinically, the furthest in development is ibrutinib (trade name, Imbruvica), an irreversible BTKi, which has shown spectacular preliminary efficacy, with rapid reductions in lymph nodes accompanied by peripheral blood lymphocytosis. The lymphocytosis resolves slowly and most patients do not enter a complete remission. Nevertheless, it is possible to maintain many CLL patients, even those with adverse cytogenetic features, on drug for many months with minimal toxicities, thus potentially transforming the therapeutic paradigms for CLL. The efficacy, lack of toxicity and oral administration of BTKi will ensure their adoption in a wide range of B cell malignancies. An outstanding challenge is to incorporate BTKi with other precision medicines in a mechanism-based manner in order to dispense with conventional chemotherapy.