Results of several investigations indicate that eye movements can reveal memory for elements of previous experience. These effects of memory on eye movement behavior can emerge very rapidly, changing the efficiency and even the nature of visual processing without appealing to verbal reports and without requiring conscious recollection. This aspect of eye movement based memory investigations is particularly useful when eye movement methods are used with special populations (e.g., young children, elderly individuals, and patients with severe amnesia), and also permits use of comparable paradigms in animals and humans, helping to bridge different memory literatures and permitting cross-species generalizations. Unique characteristics of eye movement methods have produced findings that challenge long-held views about the nature of memory, its organization in the brain, and its failures in special populations. Recently, eye movement methods have been successfully combined with neuroimaging techniques such as fMRI, single-unit recording, and magnetoencephalography, permitting more sophisticated investigations of memory. Ultimately, combined use of eye-tracking with neuropsychological and neuroimaging methods promises to provide a more comprehensive account of brain–behavior relationships and adheres to the “converging evidence” approach to cognitive neuroscience.

Hubs are network components that hold positions of high importance for network function. Previous research has identified hubs in human brain networks derived from neuroimaging data; however, there is little consensus on the localization of such hubs. Moreover, direct evidence regarding the role of various proposed hubs in network function (e.g., cognition) is scarce. Regions of the default mode network (DMN) have been frequently identified as "cortical hubs" of brain networks. On theoretical grounds, we have argued against some of the methods used to identify these hubs and have advocated alternative approaches that identify different regions of cortex as hubs. Our framework predicts that our proposed hub locations may play influential roles in multiple aspects of cognition, and, in contrast, that hubs identified via other methods (including salient regions in the DMN) might not exert such broad influence. Here we used a neuropsychological approach to directly test these predictions by studying long-term cognitive and behavioral outcomes in 30 patients, 19 with focal lesions to six "target" hubs identified by our approaches (high system density and participation coefficient) and 11 with focal lesions to two "control" hubs (high degree centrality). In support of our predictions, we found that damage to target locations produced severe and widespread cognitive deficits, whereas damage to control locations produced more circumscribed deficits. These findings support our interpretation of how neuroimaging-derived network measures relate to cognition and augment classic neuroanatomically based predictions about cognitive and behavioral outcomes after focal brain injury.functional connectivity | neuropsychology | fMRI | brain hubs T he careful description of circumscribed cognitive and behavioral deficits following localized brain damage has provided much of our knowledge of the functional geography of the brain. In some cases, however, relatively small, circumscribed lesions seem to have broader effects than would be predicted from their size and location. Historically, these effects sometimes have been attributed to diaschisis (i.e., effects at a distance) owing to connections between affected and unaffected brain regions. The potential importance of interactivity among brain regions is supported by recent research (1-3); for example, He et al. (4) found that visuospatial inattention after right inferior parietal lesions was best explained by the effects of those lesions on more superior parietal activity.In the broadest sense, interactive explanations of brain function can be thought of as reflecting the organization of the brain as a large-scale network. The advent of large-scale network descriptions of brain structure and function extends the possibility of richer and broader explanations of unusually severe cognitive and behavioral consequences that sometimes follow circumscribed lesions. Some large-scale network studies have focused on "hubs," a term from network science that indicates potential points of impo...

Relational memory theory holds that the hippocampus supports, and amnesia following hippocampal damage impairs, memory for all manner of relations. Unfortunately, many studies of hippocampal-dependent memory have either examined only a single type of relational memory or confl ated multiple kinds of relations. The experiments reported here employed a procedure in which each of several kinds of relational memory (spatial, associative, and sequential) could be tested separately using the same materials. In Experiment 1, performance of amnesic patients with medial temporal lobe (MTL) damage was assessed on memory for the three types of relations as well as for items. Compared to the performance of matched comparison participants, amnesic patients were impaired on all three relational tasks. But for those patients whose MTL damage was limited to the hippocampus, performance was relatively preserved on item memory as compared to relational memory, although still lower than that of comparison participants. In Experiment 2, study exposure was reduced for comparison participants, matching their item memory to the amnesic patients in Experiment 1. Relational memory performance of comparison subjects was well above amnesic patient levels, showing the disproportionate dependence of all three relational memory performances on the integrity of the hippocampus. Correlational analyses of the various task performances of comparison participants and of college-age participants showed that our measures of item memory were not infl uenced signifi cantly by memory for associations among the items.

Hippocampal damage causes profound yet circumscribed memory impairment across diverse stimulus types and testing formats. Here, within a single test format involving a single class of stimuli, we identified different performance errors to better characterize the specifics of the underlying deficit. The task involved study and reconstruction of object arrays across brief retention intervals. The most striking feature of patients’ with hippocampal damage performance was that they tended to reverse the relative positions of item pairs within arrays of any size, effectively “swapping” pairs of objects. These “swap errors” were the primary error type in amnesia, almost never occurred in healthy comparison participants, and actually contributed to poor performance on more traditional metrics (such as distance between studied and reconstructed location). Patients made swap errors even in trials involving only a single pair of objects. The selectivity and severity of this particular deficit creates serious challenges for theories of memory and hippocampus.

Effective exploratory behaviors involve continuous updating of sensory sampling to optimize the efficacy of information gathering. Despite some work on this issue in animals, little information exists regarding the cognitive or neural mechanisms for this sort of behavioral optimization in humans. Here we examined a visual exploration phenomenon that occurred when human subjects studying an array of objects spontaneously looked "backward" in their scanning paths to view recently seen objects again. This "spontaneous revisitation" of recently viewed objects was associated with enhanced hippocampal activity and superior subsequent memory performance in healthy participants, but occurred only rarely in amnesic patients with severe damage to the hippocampus. These findings demonstrate the necessity of the hippocampus not just in the aspects of long-term memory with which it has been associated previously, but also in the short-term adaptive control of behavior. Functional neuroimaging showed hippocampal engagement occurring in conjunction with frontocerebellar circuits, thereby revealing some of the larger brain circuitry essential for the strategic deployment of information-seeking behaviors that optimize learning.amnesia | prefrontal cortex | vicarious trial-and-error behavior O ne of the hallmarks of higher cognitive functioning is the ability to flexibly tailor behaviors to current situational demands. An example comes from the purposeful way animals explore the environment, effectively sampling the particular information most critical for learning and later memory. A number of investigators have emphasized the critical role in such behaviors of memory systems (1, 2) and strategic/executive control systems (3, 4). Some theorizing about exploratory behaviors has emphasized the potential importance of constant iteration between perception and action (5, 6) or between prediction and verification (7-9). However, little is known, at least in humans, about precisely how processing in neural systems leads to the optimization of exploratory behaviors and how the behaviors, in turn, affect processing in these systems as learning occurs. This is partially because contemporary research often involves exposing individuals to some information and relating brain activity to the ability to later recall or recognize aspects of the original learning event (10). Findings therefore primarily concern processes closely allied with introspective reports rather than the processes by which memory signals are used by the organism in the moment-tomoment guidance of dynamic behavior.Connections between brain activity and ongoing behavior are generally better understood in animals, in which the assaying of active behaviors is a necessity for studying learning and memory.* For the work reported here, one notable example is a phenomenon in rodents described by Muenzinger (13) and Tolman (7-9) that seems to relate memory processing and exploratory behavior. When learning to discriminate between two stimuli based on one item's selective associa...

ImportanceSARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.ObjectiveTo develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.Design, Setting, and ParticipantsProspective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.ExposureSARS-CoV-2 infection.Main Outcomes and MeasuresPASC and 44 participant-reported symptoms (with severity thresholds).ResultsA total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.Conclusions and RelevanceA definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

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The prospective, multisite human immunodeficiency (HIV) Epidemiology Research Study was established to define the biologic, psychologic, and social effects of HIV infection on the health of US women. From 1993 to 1995, a total of 871 HIV-infected women and 439 demographically matched, uninfected women aged 16-55 years, half of whom reported injection drug use and half of whom reported only sexual risk behaviors, were recruited in four US cities. Two sites recruited primarily from medical/drug therapy care settings, and two recruited from community sources. Women consented to biannual interviews; physical examination; blood, urine, and cervicovaginal specimen collection and repository; laboratory assays; and abstraction of outpatient and inpatient medical records to document HIV and acquired immunodeficiency syndrome-related diagnoses. Retention was greater than 88% at the third 6-month follow-up. Lower retention was associated with currently injecting drugs, not having dependent children, and not being infected with HIV at enrollment. In addition to the core study, a variety of nested studies are under way, some in collaboration with other HIV cohorts and various Public Health Service agencies. This cohort is distinct from other HIV longitudinal cohorts in the diversity of its participants and the comprehensive range of measures to study prospectively the biomedical, social, and emotional effects of the HIV epidemic on infected women and those whose behavior puts them at high risk of infection.