Project description:There is a consensus that visual working memory (WM) resources are sharply limited, but debate persists regarding the simple question of whether there is a limit to the total number of items that can be stored concurrently. Zhang and Luck (2008) advanced this debate with an analytic procedure that provided strong evidence for random guessing responses, but their findings can also be described by models that deny guessing while asserting a high prevalence of low precision memories. Here, we used a whole report memory procedure in which subjects reported all items in each trial and indicated whether they were guessing with each response. Critically, this procedure allowed us to measure memory performance for all items in each trial. When subjects were asked to remember 6 items, the response error distributions for about 3 out of the 6 items were best fit by a parameter-free guessing model (i.e. a uniform distribution). In addition, subjects' self-reports of guessing precisely tracked the guessing rate estimated with a mixture model. Control experiments determined that guessing behavior was not due to output interference, and that there was still a high prevalence of guessing when subjects were instructed not to guess. Our novel approach yielded evidence that guesses, not low-precision representations, best explain limitations in working memory. These guesses also corroborate a capacity-limited working memory system - we found evidence that subjects are able to report non-zero information for only 3-4 items. Thus, WM capacity is constrained by an item limit that precludes the storage of more than 3-4 individuated feature values.
Project description:Research into human working memory limits has been shaped by the competition between different formal models, with a central point of contention being whether internal representations are continuous or discrete. Here we describe a sampling approach derived from principles of neural coding as a framework to understand working memory limits. Reconceptualizing existing models in these terms reveals strong commonalities between seemingly opposing accounts, but also allows us to identify specific points of difference. We show that the discrete versus continuous nature of sampling is not critical to model fits, but that, instead, random variability in sample counts is the key to reproducing human performance in both single- and whole-report tasks. A probabilistic limit on the number of items successfully retrieved is an emergent property of stochastic sampling, requiring no explicit mechanism to enforce it. These findings resolve discrepancies between previous accounts and establish a unified computational framework for working memory that is compatible with neural principles.
Project description:A dominant view of prefrontal cortex (PFC) function is that it stores task-relevant information in working memory. To examine this and determine how it applies when multiple pieces of information must be stored, we trained two subjects to perform a multi-item color change detection task and recorded activity of neurons in PFC. Few neurons encoded the color of the items. Instead, the predominant encoding was spatial: a static signal reflecting the item's position and a dynamic signal reflecting the subject's covert attention. These findings challenge the notion that PFC stores task-relevant information. Instead, we suggest that the contribution of PFC is in controlling the allocation of resources to support working memory. In support of this, we found that increased power in the alpha and theta bands of PFC local field potentials, which are thought to reflect long-range communication with other brain areas, was correlated with more precise color representations.
Project description:Investigations of working memory capacity in the visual domain have converged on the concept of a limited supply of a representational medium, flexibly distributed between objects. Current debate centers on whether this medium is continuous, or quantized into 2 or 3 memory "slots". The latter model makes the strong prediction that, if an item in memory is probed, behavioral parameters will plateau when the number of items is the same or more than the number of slots. Here we examine short-term memory for object location using a two-dimensional pointing task. We show that recall variability for items in memory increases monotonically from 1 to 8 items. Using a novel method to isolate only those trials on which a participant correctly identifies the target, we show that response latency also increases monotonically from 1 to 8 items. We argue that both these findings are incompatible with a quantized model.
Project description:I propose that the capacity of working memory places a specific limit on the maintenance of temporary bindings. Two experiments support this binding hypothesis: Participants remembered word lists of varying length. When tested on a randomly selected word, their error rates increased with the length of the list, reflecting a limited capacity for short-term maintenance. This increase in errors was predominantly due to binding errors: People confused the correct word with other words of the current memory list, but very rarely with words not in the list. The frequencies of response choices were analyzed through two measurement models - one based on the assumption of discrete memory states, one on the assumption of continuous memory strength - that capture memory for items and for bindings in separate parameters. Increasing memory set size impaired binding memory but not item memory, supporting the binding hypothesis.
Project description:Humans can flexibly transfer information between different memory systems. Information in visual working memory (VWM) can for instance be stored in long-term memory (LTM). Conversely, information can be retrieved from LTM and temporarily held in WM when needed. It has previously been suggested that a neural transition from parietal- to midfrontal activity during repeated visual search reflects transfer of information from WM to LTM. Whether this neural transition indeed reflects consolidation and is also observed when memorizing a rich visual scene (rather than responding to a single target), is not known. To investigate this, we employed an EEG paradigm, in which abstract six-item colour-arrays were repeatedly memorized and explicitly visualized, or merely attended to. Importantly, we tested the functional significance of a potential neural shift for longer-term consolidation in a subsequent recognition task. Our results show a gradually enhanced- and sustained modulation of the midfrontal P170 component and a decline in parietal CDA, during repeated WM maintenance. Improved recollection/visualization of memoranda upon WM-cueing, was associated with contralateral parietal- and right temporal activity. Importantly, only colour-arrays previously held in WM, induced a greater midfrontal P170-response, together with left temporal- and late centro-parietal activity, upon re-exposure. These findings provide evidence for recruitment of an LTM-supporting neural network which facilitates visual WM maintenance.
Project description:Chronic innate immune activation in the central nervous system (CNS) significantly contributes to neurodegeneration in progressive multiple sclerosis (MS). Using multiple EAE models, we explored the potential of the innate immune sensor NLRX1 to protect neurons in the anterior visual pathway from inflammatory neurodegeneration. To do this, we assessed retinal ganglion cell (RGC) density and optic nerve axonal degeneration, gliosis, and T-cell infiltration in Nlrx1-/- and wild-type (WT) EAE mice. Our results indicate that Nlrx1-/- mice exhibit significantly increased RGC loss and axonal injury compared to WT mice in both active immunization EAE and spontaneous opticospinal encephalomyelitis models. Adoptive transfer experiments, in which wild type T cells were transferred into lymphocyte-deficient Rag-/- mice to minimize the effects of Nlrx1 knockout on peripheral lymphocyte priming, revealed more severe microgliosis and astrogliosis in the optic nerve of Nlrx1-/-Rag-/- mice compared to Rag-/- mice, suggesting a regulatory role of NLRX1 in innate immune compartments. Transcriptome analysis in primary astrocytes demonstrated that NLRX1 negatively regulates TLR-mediated NF-κB activation. The novel pharmacologic NLRX1 activator LABP-66 decreased LPS-mediated gene expression of inflammatory cytokines and chemokines in mixed glial cultures. Moreover, treating EAE mice with oral LABP-66 after the onset of paralysis resulted in less anterior visual pathway neurodegeneration compared to vehicle. These data suggest that a pharmacologic NLRX1 activators attenuates glial immune activation and has the potential to limit inflammatory neurodegeneration in diseases, such as MS, where chronic CNS-compartmentalized inflammation may drive neurodegenerative pathology. This study highlights that NLRX1 could serve as a promising target for neuroprotection in progressive MS and other neurodegenerative diseases where chronic compartmentalized innate immune activation and neuroinflammation play a role.
Project description:Recent findings indicate that the hippocampus supports not only long-term memory encoding but also plays a role in working memory (WM) maintenance of multiple items; however, the neural mechanism underlying multi-item maintenance is still unclear. Theoretical work suggests that multiple items are being maintained by neural assemblies synchronized in the gamma frequency range (25-100 Hz) that are locked to consecutive phase ranges of oscillatory activity in the theta frequency range (4-8 Hz). Indeed, cross-frequency coupling of the amplitude of high-frequency activity to the phase of slower oscillations has been described both in animals and in humans, but has never been linked to a theoretical model of a cognitive process. Here we used intracranial EEG recordings in human epilepsy patients to test pivotal predictions from theoretical work. First, we show that simultaneous maintenance of multiple items in WM is accompanied by cross-frequency coupling of oscillatory activity in the hippocampus, which is recruited during multi-item WM. Second, maintenance of an increasing number of items is associated with modulation of beta/gamma amplitude with theta band activity of lower frequency, consistent with the idea that longer cycles are required for an increased number of representations by gamma cycles. This effect cannot be explained by a difference in theta or beta/gamma power. Third, we describe how the precision of cross-frequency coupling predicts individual WM performance. These data support the idea that working memory in humans depends on a neural code using phase information.
Project description:There has been considerable controversy in recent years as to whether information held in working memory (WM) is rapidly forgotten or automatically transferred to long-term memory (LTM). Although visual WM capacity is very limited, we appear able to store a virtually infinite amount of information in visual LTM. Still, LTM retrieval often fails. Some view visual WM as a mental sketchpad that is wiped clean when new information enters, but not a consistent precursor of LTM. Others view the WM and LTM systems as inherently linked. Distinguishing between these possibilities has been difficult, as attempts to directly manipulate the active holding of information in visual WM has typically introduced various confounds. Here, we capitalized on the WM system's capacity limitation to control the likelihood that visual information was actively held in WM. Our young-adult participants (N = 103) performed a WM task with unique everyday items, presented in groups of two, four, six, or eight items. Presentation time was adjusted according to the number of items. Subsequently, we tested participants' LTM for items from the WM task. LTM was better for items presented originally within smaller WM set sizes, indicating that WM limitations contribute to subsequent LTM failures, and that holding items in WM enhances LTM encoding. Our results suggest that a limit in WM capacity contributes to an LTM encoding bottleneck for trial-unique familiar objects, with a relatively large effect size.