Examining the roles of visual imagery and working memory in the retrieval of autobiographical memories using a dual-task paradigm.

The retrieval of autobiographical memories involves the construction of mental representations of past personal events. Many researchers examining the processes underlying memory retrieval argue that visual imagery plays a fundamental role. Other researchers, however, have argued that working memory is an integral component involved in memory retrieval. The goal of this study was to resolve these conflicting arguments by comparing the relative contributions of visual imagery and working memory during the retrieval of autobiographical memories in a dual-task paradigm. While following a moving dot, viewing a dynamic visual noise (DVN), or viewing a blank screen, 95 participants recalled their memories and subsequently rated them on different memory characteristics. The results suggest that inhibiting visual imagery by having participants view DVN merely delayed memory retrieval but did not affect the phenomenological quality of the memories retrieved. Taxations to the working memory by having participants follow a moving dot, on the contrary, resulted in only longer retrieval latencies and no reductions in the specificity, vividness, or the emotional intensity of the memories retrieved. Whereas the role of visual imagery during retrieval is clear, future studies could further examine the role of working memory during retrieval by administering a task that is less difficult or by recruiting a larger sample than this study. The results of this study seem to suggest that both visual imagery and working memory play a role during the retrieval of autobiographical memory, but more research needs to be conducted to determine their exact roles.

Orthography-phonology consistency in English: Theory- and data-driven measures and their impact on auditory vs. visual word recognition.

Research on orthographic consistency in English words has selectively identified different sub-syllabic units in isolation (grapheme, onset, vowel, coda, rime), yet there is no comprehensive assessment of how these measures affect word identification when taken together. To study which aspects of consistency are more psychologically relevant, we investigated their independent and composite effects on human reading behavior using large-scale databases. Study 1 found effects on adults' naming responses of both feedforward consistency (orthography to phonology) and feedback consistency (phonology to orthography). Study 2 found feedback but no feedforward consistency effects on visual and auditory lexical decision tasks, with the best predictor being a composite measure of consistency across grapheme, rime, OVC, and word-initial letter-phoneme. In Study 3, we explicitly modeled the reading process with forward and backward flow in a bidirectionally connected neural network. The model captured latent dimensions of quasi-regular mapping that explain additional variance in human reading and spelling behavior, compared to the established measures. Together, the results suggest interactive activation between phonological and orthographic word representations. They also validate the role of computational analyses of language to better understand how print maps to sound, and what properties of natural language affect reading complexity.

Is the Mind Inherently Predicting? Exploring Forward and Backward Looking in Language Processing.

Prediction is one characteristic of the human mind. But what does it mean to say the mind is a "prediction machine" and inherently forward looking as is frequently claimed? In natural languages, many contexts are not easily predictable in a forward fashion. In English, for example, many frequent verbs do not carry unique meaning on their own but instead, rely on another word or words that follow them to become meaningful. Upon reading take a the processor often cannot easily predict walk as the next word. But the system can "look back" and integrate walk more easily when it follows take a (e.g., as opposed to *make|get|have a walk). In the present paper, we provide further evidence for the importance of both forward and backward-looking in language processing. In two self-paced reading tasks and an eye-tracking reading task, we found evidence that adult English native speakers' sensitivity to word forward and backward conditional probability significantly predicted reading times over and above psycholinguistic predictors of reading latencies. We conclude that both forward and backward-looking (prediction and integration) appear to be important characteristics of language processing. Our results thus suggest that it makes just as much sense to call the mind an "integration machine" which is inherently backward 'looking.'

Replicating remembering "remembering".

When examining spontaneously recovered memories of childhood sexual abuse, victims report that there had been periods in which they had forgotten the abuse. However, there are sometimes people with whom the victim had spoken about the abuse during the period in which the victim had supposedly forgotten the abuse, suggesting the victim had not forgotten the abuse but the prior recall of the abuse. The underestimation of previous knowledge is termed the forgot-it-all-along effect. The goal of the present study was replicating the results of a laboratory study that had provided a theoretical understanding for the forgot-it-all-along effect by showing that people have difficulties remembering "remembering" when the memory had previously been recalled in a different context. The effect was replicated by using the same neutral context sentences, suggesting the finding was robust. We also extended the experimental design by using positive and negative context sentences, but it did not become smaller when the positive sentences provided the different context or larger when the negative sentences provided the different context. Although the sample sizes were sufficiently large to provide statistical power for the forgot-it-all-along effect, they may not have been sufficiently large to observe the moderation effects of emotional context.

Looking at remembering: Eye movements, pupil size, and autobiographical memory.

To examine the relationship between visual imagery and autobiographical memory, eye position and pupil size were recorded while participants first searched for memories and then reconstructed the retrieved memories (Experiment 1), or only searched for memories (Experiment 2). In Experiment 1, we observed that, although recollective experience was not associated with the number of fixations per minute, memories that took longer to retrieve were linked to increased pupil size. In Experiment 2, we observed that directly retrieved memories were recalled more quickly and were accompanied by smaller pupils than generatively retrieved memories. After correcting for response time, retrieval mode also produced an effect, showing that decreased pupil size is not simply due to directly retrieved memories being recalled more quickly. These findings provide compelling evidence that objective measures, such as pupil size, can be used alongside subjective measures, such as self-reports, to distinguish between directly retrieved and generatively retrieved memories.

RORα is a critical checkpoint for T cell and ILC2 commitment in the embryonic thymus.

Type 2 innate lymphoid cells (ILC2) contribute to immune homeostasis, protective immunity and tissue repair. Here we demonstrate that functional ILC2 cells can arise in the embryonic thymus from shared T cell precursors, preceding the emergence of CD4+CD8+ (double-positive) T cells. Thymic ILC2 cells migrated to mucosal tissues, with colonization of the intestinal lamina propria. Expression of the transcription factor RORα repressed T cell development while promoting ILC2 development in the thymus. From RNA-seq, assay for transposase-accessible chromatin sequencing (ATAC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq) data, we propose a revised transcriptional circuit to explain the co-development of T cells and ILC2 cells from common progenitors in the thymus. When Notch signaling is present, BCL11B dampens Nfil3 and Id2 expression, permitting E protein-directed T cell commitment. However, concomitant expression of RORα overrides the repression of Nfil3 and Id2 repression, allowing ID2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORα expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus.

Exploring the temporal dynamics of inhibition of return using steady-state visual evoked potentials.

Inhibition of return is characterized by delayed responses to previously attended locations when the interval between stimuli is long enough. The present study employed steady-state visual evoked potentials (SSVEPs) as a measure of attentional modulation to explore the nature and time course of input- and output-based inhibitory cueing mechanisms that each slow response times at previously stimulated locations under different experimental conditions. The neural effects of behavioral inhibition were examined by comparing post-cue SSVEPs between cued and uncued locations measured across two tasks that differed only in the response modality (saccadic or manual response to targets). Grand averages of SSVEP amplitudes for each condition showed a reduction in amplitude at cued locations in the window of 100-500 ms post-cue, revealing an early, short-term decrease in the responses of neurons that can be attributed to sensory adaptation, regardless of response modality. Because primary visual cortex has been found to be one of the major sources of SSVEP signals, the results suggest that the SSVEP modulations observed were caused by input-based inhibition that occurred in V1, or visual areas earlier than V1, as a consequence of reduced visual input activity at previously cued locations. No SSVEP modulations were observed in either response condition late in the cue-target interval, suggesting that neither late input- nor output-based IOR modulates SSVEPs. These findings provide further electrophysiological support for the theory of multiple mechanisms contributing to behavioral cueing effects.

Response Priming with Horizontally and Vertically Moving Primes: A Comparison of German, Malaysian, and Japanese Subjects.

Response priming refers to the finding that a prime preceding a target influences the response to the target. With German subjects, horizontally moving dots as primes, and static arrows as targets, there are typically faster responses to compatible (i.e., prime and target are associated with the same response) as compared to incompatible targets (i.e., positive compatibility effect, PCE) with short stimulus onset asynchronies (SOAs). In contrast, with longer SOAs, subjects respond faster to incompatible as compared to compatible targets (i.e., negative compatibility effect, NCE). In the present study, we extended the evidence by adding vertically oriented materials. Furthermore, we tested subjects from Malaysia and Japan, where the vertical orientation is more present in daily life, and compared them to German subjects to investigate whether the amount of experience with one orientation influences the compatibility effects on this orientation. Overall, we found pronounced PCEs in the short SOA (i.e., 150 ms) but only reduced PCEs in the longer SOAs (i.e., 350, 550, and 750 ms) across all countries and orientations. There were no differences between the German and Malaysian samples, but the Japanese sample showed larger PCEs in the longer SOAs compared to both other samples. Furthermore, we found larger PCEs for horizontal than vertical materials in the short SOA and larger PCEs for vertical than horizontal materials in the longer SOAs. We discuss our findings in light of theories and findings on compatibility effects as well as attentional mechanisms.

Inhibitory and Facilitatory Cueing Effects: Competition between Exogenous and Endogenous Mechanisms.

Inhibition of return is characterized by delayed responses to previously attended locations when the cue-target onset asynchrony (CTOA) is long enough. However, when cues are predictive of a target's location, faster reaction times to cued as compared to uncued targets are normally observed. In this series of experiments investigating saccadic reaction times, we manipulated the cue predictability to 25% (counterpredictive), 50% (nonpredictive), and 75% (predictive) to investigate the interaction between predictive endogenous facilitatory (FCEs) and inhibitory cueing effects (ICEs). Overall, larger ICEs were seen in the counterpredictive condition than in the nonpredictive condition, and no ICE was found in the predictive condition. Based on the hypothesized additivity of FCEs and ICEs, we reasoned that the null ICEs observed in the predictive condition are the result of two opposing mechanisms balancing each other out, and the large ICEs observed with counterpredictive cueing can be attributed to the combination of endogenous facilitation at uncued locations with inhibition at cued locations. Our findings suggest that the endogenous activity contributed by cue predictability can reduce the overall inhibition observed when the mechanisms occur at the same location, or enhance behavioral inhibition when the mechanisms occur at opposite locations.

Sensory adaptation and inhibition of return: dissociating multiple inhibitory cueing effects.

Inhibition of return (IOR) refers to an increase in reaction times to targets that appeared at a previously cued location relative to an uncued location, often investigated using a spatial cueing paradigm. Despite numerous studies that have examined many aspects of IOR, the neurophysiological mechanisms underlying IOR are still in dispute. The objective of the current research is to investigate the plausible mechanisms by manipulating the cue and target types between central and peripheral stimuli in a traditional cue-target paradigm with saccadic responses to targets. In peripheral-cueing conditions, we observed inhibitory cueing effects across all cue-target onset asynchronies (CTOAs) with peripheral targets, but IOR was smaller and arose later with central targets. No inhibition was observed in central-cueing conditions at any CTOAs. Empirical data were simulated using a two-dimensional dynamic neural field model. Our results and simulations support previous work demonstrating that, at short CTOAs, behavioral inhibition is only observed with repeated stimulation-an effect of sensory adaptation. With longer CTOAs, IOR is observed regardless of target type when peripheral cueing is used. Our findings suggest that behaviorally exhibited inhibitory cueing effects can be attributed to multiple mechanisms, including both attenuation of visual stimulation and local inhibition in the superior colliculus.

Time course of inhibition of return in a spatial cueing paradigm with distractors.

Studies of endogenous and exogenous attentional orienting in spatial cueing paradigms have been used to investigate inhibition of return, a behavioral phenomenon characterized by delayed reaction time in response to recently attended locations. When eye movements are suppressed, attention is covertly oriented to central or peripheral stimuli. Overt orienting, on the other hand, requires explicit eye movements to the stimuli. The present study examined the time course of slowed reaction times to previously attended locations when distractors are introduced into overt and covert orienting tasks. In a series of experiments, manual responses were required to targets following central and peripheral cues at three different cue-target intervals, with and without activated oculomotor systems. The results demonstrate that, when eye movements are suppressed, behavioral inhibition is reduced or delayed in magnitude by the presence of a distractor relative to conditions without distractors. However, the time course of behavioral inhibition when eye movements are required remains similar with or without distractors.

Stimulus-response incompatibility eliminates inhibitory cueing effects with saccadic but not manual responses.

There are thought to be two forms of inhibition of return (IOR) depending on whether the oculomotor system is activated or suppressed. When saccades are allowed, output-based IOR is generated, whereas input-based IOR arises when saccades are prohibited. In a series of 4 experiments, we mixed or blocked compatible and incompatible trials with saccadic or manual responses to investigate whether cueing effects would follow the same pattern as those observed with more traditional peripheral onsets and central arrows. In all experiments, an uninformative cue was displayed, followed by a cue-back stimulus that was either red or green, indicating whether a compatible or incompatible response was required. The results showed that IOR was indeed observed for compatible responses in all tasks, whereas IOR was eliminated for incompatible trials-but only with saccadic responses. These findings indicate that the dissociation between input- and output-based forms of IOR depends on more than just oculomotor activation, providing further support for the existence of an inhibitory cueing effect that is distinct to the manual response modality.

Directed evolution of human scFvs in DT40 cells.

Cells that constitutively diversify their immunoglobulin genes can be used for selection of novel antibodies and for refining existing affinities and specificities. Here, we report an adaptation of the chicken DT40 system wherein its capacity for somatic hypermutation is harnessed to evolve human antibodies expressed as single-chain variable fragments (scFvs). Expression of membrane-anchored scFvs from within the rearranged Igλ locus created self-diversifying scFv libraries from which we could both select scFvs of a desired specificity and evolve both the specificity and affinity of existing scFvs by iterative expansion and selection. From these scFvs, we were able to create fully human IgG antibodies with nanomolar affinities. We further enhanced the functionality of the system by creating a pool of DT40 scFv lines with high levels of mutation driven by the overexpression of a hyperactive variant of activation-induced deaminase. From this library, we successfully isolated scFvs that bound the spliceosome factor CWC15 and the cytokine human IFNγ. Our results demonstrate the flexibility and utility of DT40 for rapid generation of scFv repertoires and efficient selection, evolution and affinity maturation of scFv specificities.