Multitasking negatively influences the retention of information over brief periods of time. This impact of interference on working memory is exacerbated with normal aging. We used functional MRI to investigate the neural basis by which an interruption is more disruptive to working memory performance in older individuals. Younger and older adults engaged in delayed recognition tasks both with and without interruption by a secondary task. Behavioral analysis revealed that working memory performance was more impaired by interruptions in older compared with younger adults. Functional connectivity analyses showed that when interrupted, older adults disengaged from a memory maintenance network and reallocated attentional resources toward the interrupting stimulus in a manner consistent with younger adults. However, unlike younger individuals, older adults failed to both disengage from the interruption and reestablish functional connections associated with the disrupted memory network. These results suggest that multitasking leads to more significant working memory disruption in older adults because of an interruption recovery failure, manifest as a deficient ability to dynamically switch between functional brainnetworks.W orking memory (WM), the ability to store and manipulate information in the mind over brief periods of time, is critical for a wide variety of cognitive abilities and real life activities (1). It has been demonstrated that WM performance is negatively impacted by the presence of external stimuli that are outside the focus of our memory goals (2, 3). This interference occurs whether there is an attempt to ignore these stimuli (i.e., distractions), or attend to them as a component of a concurrent, secondary task (i.e., interruptions, or multitasking) (4). We recently showed that older adults experience a more negative impact by distraction on WM performance compared with younger adults, and an even greater impairment when multitasking (5). There is extensive literature indicating that older adults are highly susceptible to distraction and that this leads to impairment in performance (for review, see refs. 6 and 7). In terms of a greater impact of multitasking on WM in aging, this finding is consistent with the detrimental influence that multitasking has been shown to have on a wide range of activities in older individuals (8-10). Research directed at understanding the basis of age-related interference effects is becoming increasingly important, as older adults remain engaged in the work force later in life (11), which itself is evolving into a more demanding, high-interference environment (12).To explore the neural basis of age-related WM disruption by distractions, we previously conducted a series of experiments using electroencephalography (EEG) and functional MRI (fMRI) recordings. Functional MRI measures revealed that older individuals inappropriately direct excessive attention toward processing visual stimuli that are entirely irrelevant (i.e., distractions), and that this correlates with diminishe...

Glaucoma is a leading cause of blindness worldwide, and is characterized by progressive retinal ganglion cell (RGC) death. An experimental model of glaucoma has been established by elevating the intraocular pressure (IOP) via microbead occlusion of ocular fluid outflow in mice. Studies in this model have found visual dysfunction that varied with adaptational state, occurred before anatomical changes, and affected OFF RGCs more than ON RGCs. These results indicate subtle alterations in the underlying retinal circuitry that could help identify disease before irreversible RGC changes. Therefore, we looked at how RGC function was altered with elevated IOP under both photopic and scotopic conditions. We first found that responses to light offset are diminished with IOP elevation along with a concomitant decrease in receptive field center size for OFF RGCs. In addition, the antagonistic surround strength and size was reduced in ON RGCs. Furthermore, elevation of IOP significantly accelerated the photopic temporal tuning of RGC center responses in both ON and OFF RGCs. We found that some of the IOP-induced functional changes to OFF RGCs relied on ON cross-over pathways, indicating dysfunction in inner retinal circuitry. Overall, these results suggest that IOP alters multiple functions in the retina depending on the adaptational state. They provide a basis for designing multiple functional tests for early detection of glaucoma and for circuit-specific therapeutic targets in treatment of this blinding disease.retinal ganglion cell | glaucoma | IOP | receptive field | multielectrode array G laucoma is one of the leading causes of blindness worldwide (1). It is a progressive disease and most patients are only identified after an irreversible visual deficit is already present (2). Diagnosing patients with subtle functional deficits that occur before this irreversible visual deficit will significantly improve a patient's ability to preserve normal vision.Elevated intraocular pressure (IOP) is a critical risk factor for glaucoma and the central focus of glaucoma treatment (3, 4). Mouse models of glaucoma are also dependent on raising IOP. One method to elevate IOP is to inject microbeads into the eye to block normal fluid outflow (5). Previous studies on this mouse model have found that high IOP causes changes in retinal ganglion cell (RGC) anatomy and eventual cell death leading to irreversible vision loss as seen in glaucoma (5-7). Before these changes, functional properties, such as RGC light sensitivity and photopic receptive field (RF) center size, are altered (8-12). A better understanding of these functional changes may help to detect human disease before irreversible cell death.In addition to RGC changes, behavioral tests have found that spatiotemporal tuning under photopic and scotopic conditions is altered (10). These behavioral studies suggest alteration in additional functional properties related to spatiotemporal tuning, such as scotopic receptive field size, temporal tuning, and the antagonistic surround.To det...

Elevation of intraocular pressure (IOP) causes retinal ganglion cell (RGC) dysfunction and death and is a major risk factor for glaucoma. We used a bead injection technique to increase IOP in mice of both genders by an average of ϳ3 mmHg for 2 weeks. This level of IOP elevation was lower than that achieved in other studies, which allowed for the study of subtle IOP effects. We used multielectrode array recordings to determine the cellular responses of RGCs exposed to this mild degree of IOP elevation. We found that RGC photopic receptive field (RF) center size and whole-field RGC firing rates were unaffected by IOP elevation. In contrast, we found that the temporal properties of RGC photopic responses in the RF center were accelerated, particularly in ON sustained cells. We also detected a loss of antagonistic surround in several RGC subtypes. Finally, spontaneous firing rate, interspike interval variance, and contrast sensitivity were altered according to the magnitude of IOP exposure and also displayed an IOP-dependent effect. Together, these results suggest that individual RGC physiologic parameters have unique IOP-related functional thresholds that exist concurrently and change following IOP elevation according to specific patterns. Furthermore, even subtle IOP elevation can impart profound changes in RGC function, which in some cases may occur in an IOP-dependent manner. This system of overlapping functional thresholds likely underlies the complex effects of elevated IOP on the retina.

Reverse correlation methods such as spike‐triggered averaging consistently identify the spatial center in the linear receptive fields (RFs) of retinal ganglion cells (GCs). However, the spatial antagonistic surround observed in classical experiments has proven more elusive. Tests for the antagonistic surround have heretofore relied on models that make questionable simplifying assumptions such as space–time separability and radial homogeneity/symmetry. We circumvented these, along with other common assumptions, and observed a linear antagonistic surround in 754 of 805 mouse GCs. By characterizing the RF's space–time structure, we found the overall linear RF's inseparability could be accounted for both by tuning differences between the center and surround and differences within the surround. Finally, we applied this approach to characterize spatial asymmetry in the RF surround. These results shed new light on the spatiotemporal organization of GC linear RFs and highlight a major contributor to its inseparability.

The remarkable dynamic range of vision is facilitated by adaptation of retinal sensitivity to ambient lighting conditions. An important mechanism of sensitivity adaptation is control of the spatial and temporal window over which light is integrated. The retina accomplishes this by switching between parallel synaptic pathways with differing kinetics and degrees of synaptic convergence. However, the relative shifts in spatial and temporal integration are not well understood - particularly in the context of the antagonistic spatial surround. Here, we resolve these issues by characterizing the adaptation-induced changes to spatiotemporal integration in the linear receptive field center and surround of mouse retinal ganglion cells. While most ganglion cells lose their antagonistic spatial surround under scotopic conditions, a strong surround is maintained in a subset. We then applied a novel technique that allowed us to analyze the receptive field as a triphasic temporal filter in the center and a biphasic filter in the surround. The temporal tuning of the surround was relatively maintained across adaptation conditions compared to the center, which greatly increased its temporal integration. Though all phases of the center's triphasic temporal response slowed, some shifted significantly less. Additionally, adaptation differentially shifted ON and OFF pathway temporal tuning, reducing their asymmetry under scotopic conditions. Finally, spatial integration was significantly increased by dark adaptation in some cells while it decreased it in others. These findings provide novel insight into how adaptation adjusts visual information processing by altering fundamental properties of ganglion cell receptive fields, such as center-surround antagonism and space-time integration.

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Retinal ganglion cells (RGCs) are often grouped based on their functional properties. Many of these functional properties, such as receptive field (RF) size, are driven by specific retinal circuits. In this report, we determined the role of the ON bipolar cell (BC) mediated crossover circuitry in shaping the center and surround of OFF RGCs. We recorded from a large population of mouse RGCs using a multielectrode array (MEA) while pharmacologically removing the ON BC-mediated crossover circuit. OFF sustained and transient responses to whole field stimuli are lost under scotopic conditions, but maintained under photopic conditions. Though photopic light responses were grossly maintained, we found that photopic light response properties were altered. Using linear RF mapping, we found a significant reduction in the antagonistic surround and a decrease in size of the RF center. Using a novel approach to separate the distinct temporal filters present in the RF center, we see that the crossover pathway contributes specifically to the sluggish antagonistic filter in the center. These results provide new insight into the role of crossover pathways in driving RGCs and also demonstrate that the distinct inputs driving the RF center can be isolated and assayed by RGC activity.

Précis: Characteristics of the most mentioned glaucoma articles on the internet were analyzed, allowing a better understanding of the dissemination of glaucoma research to the general public. Purpose:The aim was to determine the 100 most mentioned articles on the internet in the field of glaucoma and analyze their characteristics. Materials and Methods:We identified the top 100 glaucoma articles with the highest Altmetric Attention Score (AAS), an automatically calculated metric for monitoring social media. Each article was evaluated for several characteristics including year of publication, title, journal name, journal impact factor (IF), article topic, article type, affiliation, and online mentions (news, blog, policy, Twitter, Facebook, etc.). Correlation analysis was conducted for AAS with these characteristics. Results:The selected 100 articles came from 44 journals with more than half (56%) published in ophthalmology-specific journals. There was no significant correlation between IF and number of articles in a specific journal or AAS (P > 0.1), but the number of articles in the top 100 was higher for ophthalmology journals with a higher IF (P < 0.05). Original study was the most common study type (87%), of which clinical observation study was the most common subgroup (40%). Epidemiology/risk factor and basic science were the most common article topics (each 24%), followed by medical treatment (13%). Article topics regarding medical treatment had a significantly greater AAS than other topics (P < 0.05). Of the top 5 articles, more than half (60%) were related to "Lifestyle choice" topics.Conclusions: There was no association between journal IF and AAS, consistent with previous studies. 90% of journals that had articles in the top 100 had a Twitter page. "Lifestyle choice" activities and other modifiable risk factors attracted significant online attention regarding glaucoma studies, with two of the top three most mentioned articles related to dietary intake. The present study thus provides a better understanding of online engagement with glaucoma research and the dissemination of this research to the general public.