Tracking induced forgetting across both strong and weak memory representations to test competing theories of forgetting

Here we employ a novel analysis to address the question: what causes induced forgetting of pictures? We use baseline memorability as a measure of initial memory strength to ask whether induced forgetting is due to (1) recognition practice damaging the association between the memory representation and the category cue used to activate the representation, (2) the updating of a memory trace by incorporating information about a memory probe presented during recognition practice to the stored trace, (3) inhibitory mechanisms used to resolve the conflict created when correctly selecting the practiced item activates competing exemplars, (4) a global matching model in which repeating some items will hurt memory for other items, or (5) falling into the zone of destruction, where a moderate amount of activation leads to the highest degree of forgetting. None of the accounts of forgetting tested here can comprehensively account for both the novel analyses reported here and previous data using the induced forgetting paradigm. We discuss aspects of forgetting theories that are consistent with the novel analyses and existing data, a potential solution for existing models, proposals for future directions, and considerations when incorporating memorability into models of memory.

A between-task consequence of temporal expectations

In everyday life, we often anticipate the timing of one upcoming task or event while actively engaging in another. Here, we investigated temporal expectations within such a multi-task scenario. In a visual working-memory task, we manipulated whether the onset of a working-memory probe could be predicted in time, while also embedding a simple intervening task within the delay period. We first show that working-memory performance benefitted from temporal predictability, even though an intervening task had to be completed in the interim. Moreover, temporal expectations regarding the upcoming working-memory probe additionally affected performance on the intervening task, resulting in faster responses when the memory probe was anticipated early, and slower responses when the memory probe was expected late, as compared to when it was temporally unpredictable. Because the intervening task always occurred at the same time during the memory delay, differences in performance on this intervening task are attributed to a between-task consequence of temporal expectation. Thus, we show that within multi-task settings, knowing when working-memory contents will be required for an upcoming task not only facilitates performance on the associated working-memory task, but can also influence the performance of other, intervening tasks.

Androgenic Modulation of the Chloride Transporter NKCC1 Contributes to Age-dependent Isoflurane Neurotoxicity in Male Rats

Background Cognitive deficits after perinatal anesthetic exposure are well established outcomes in animal models. This vulnerability is sex-dependent and associated with expression levels of the chloride transporters NKCC1 and KCC2. The hypothesis was that androgen signaling, NKCC1 function, and the age of isoflurane exposure are critical for the manifestation of anesthetic neurotoxicity in male rats. Methods Flutamide, an androgen receptor antagonist, was administered to male rats on postnatal days 2, 4, and 6 before 6 h of isoflurane on postnatal day 7 (ntotal = 26). Spatial and recognition memory were subsequently tested in adulthood. NKCC1 and KCC2 protein levels were measured from cortical lysates by Western blot on postnatal day 7 (ntotal = 20). Bumetanide, an NKCC1 antagonist, was injected immediately before isoflurane exposure (postnatal day 7) to study the effect of NKCC1 inhibition (ntotal = 48). To determine whether male rats remain vulnerable to anesthetic neurotoxicity as juveniles, postnatal day 14 animals were exposed to isoflurane and assessed as adults (ntotal = 30). Results Flutamide-treated male rats exposed to isoflurane successfully navigated the spatial (Barnes maze probe trial F[1, 151] = 78; P < 0.001; mean goal exploration ± SD, 6.4 ± 3.9 s) and recognition memory tasks (mean discrimination index ± SD, 0.09 ± 0.14; P = 0.003), unlike isoflurane-exposed controls. Flutamide changed expression patterns of NKCC1 (mean density ± SD: control, 1.49 ± 0.69; flutamide, 0.47 ± 0.11; P < 0.001) and KCC2 (median density [25th percentile, 75th percentile]: control, 0.23 [0.13, 0.49]; flutamide, 1.47 [1.18,1.62]; P < 0.001). Inhibiting NKCC1 with bumetanide was protective for spatial memory (probe trial F[1, 162] = 6.6; P = 0.011; mean goal time, 4.6 [7.4] s). Delaying isoflurane exposure until postnatal day 14 in males preserved spatial memory (probe trial F[1, 140] = 28; P < 0.001; mean goal time, 6.1 [7.0] s). Conclusions Vulnerability to isoflurane neurotoxicity is abolished by blocking the androgen receptor, disrupting the function of NKCC1, or delaying the time of exposure to at least 2 weeks of age in male rats. These results support a dynamic role for androgens and chloride transporter proteins in perinatal anesthetic neurotoxicity. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

A dual mechanism underlying retroactive shifts of auditory spatial attention: dissociating target- and distractor-related modulations of alpha lateralization

Attention can be allocated to mental representations to select information from working memory. To date, it remains ambiguous whether such retroactive shifts of attention involve the inhibition of irrelevant information or the prioritization of relevant information. Investigating asymmetries in posterior alpha-band oscillations during an auditory retroactive cueing task, we aimed at differentiating those mechanisms. Participants were cued to attend two out of three sounds in an upcoming sound array. Importantly, the resulting working memory representation contained one laterally and one centrally presented item. A centrally presented retro-cue then indicated the lateral, the central, or both items as further relevant for the task (comparing the cued item(s) to a memory probe). Time-frequency analysis revealed opposing patterns of alpha lateralization depending on target eccentricity: A contralateral decrease in alpha power in target lateral trials indicated the involvement of target prioritization. A contralateral increase in alpha power when the central item remained relevant (distractor lateral trials) suggested the de-prioritization of irrelevant information. No lateralization was observed when both items remained relevant, supporting the notion that auditory alpha lateralization is restricted to situations in which spatial information is task-relevant. Altogether, the data demonstrate that retroactive attentional deployment involves excitatory and inhibitory control mechanisms.

Auditory cortical alpha desynchronization prioritizes the representation of memory items during a retention period

Maintaining information in working memory normally happens in dynamic environments, with a multitude of distracting events. This is particularly evident in the auditory system, for example, when trying to memorize a telephone number during ongoing background noise. How relevant to-be-memorized information is protected against the adverse influence of a temporally predictable distractor was the main goal of the present study. For this purpose we adapted a Sternberg task variant established in the visual modality, with either a strong or a weak distracting sound presented at a fixed time during the retention period. Our behavioral analysis confirmed a small, albeit significant deterioration of memory performance in the strong distractor condition. We used a time-generalized decoding approach applied to magnetoencephalography (MEG) data to investigate the extent of memory probe-related information prior to the anticipated distractor onset and found a relative decrease for the strong distractor condition. This effect was paralleled by a pre-distractor alpha power decrease in the left superior temporal gyrus (STG), a cortical region putatively holding memory content relevant information. Based on gating frameworks of alpha oscillations, these results could be interpreted as a failed inhibition of an anticipated strong (more salient) distractor. However, in a critical analysis we found that reduced alpha power in the left STG was associated with relatively increased memory probe-related information. Our results therefore support the view of alpha power reductions in relevant sensory (here auditory) cortical areas to be a mechanism by which to-be-remembered information is prioritized during working memory retention periods.

Persistence of Antibodies to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: 1-Year Follow-up With Memory Probe Vaccination

BackgroundWe previously reported the tolerability and immunogenicity 1 month after intramuscular administration of 2 bivalent virus-like particle (VLP)–based candidate norovirus vaccine formulations in adults. We now describe the persistence of immunity and responses to a memory probe vaccination 1 year later.MethodsA total of 454 healthy men and women aged 18–49 years in 3 equal groups received placebo (saline) or 15/50 or 50/50 vaccine formulations (ie, 15 or 50 µg of GI.1 genotype VLPs, respectively, and 50 µg of GII.4c VLPs) with MPL and Al(OH)3. Immunogenicity and safety were assessed up to day 365, when 351 participants received a memory probe vaccination of 15 µg each of GI.1 and GII.4c VLPs with Al(OH)3.ResultsNo safety signals were detected up to 1 year after the first vaccination. Pan-immunoglobulin, immunoglobulin A, and histo-blood group antigen–blocking (HBGA) antibody levels among vaccinees waned but remained higher than levels before vaccination and levels in placebo recipients on days 180 and 365. Memory probe vaccination increased all antibody titers. Levels of HBGA antibodies to GI.1 but not GII.4c were higher after the first vaccination in candidate vaccine groups, compared with those in the placebo group.ConclusionLevels of antibodies to both candidate norovirus VLP formulations persisted above baseline levels for at least 1 year after primary vaccination. HBGA-blocking responses to the memory probe for GI.1 but not GII.4c displayed characteristics of immune memory.Clinical Trials RegistrationNCT02142504.

Hierarchical structure and memory retrieval mechanisms in agreement attraction

Speakers occasionally cause the verb to agree with an element that is not the subject, a so-called ‘attractor’; likewise, comprehenders occasionally fail to notice agreement errors when the attractor agrees with the verb. Cross-linguistic studies converge in showing that attraction is modulated by the hierarchical position of the attractor in the sentence structure. We report two experiments exploring the link between structural position and memory representations in attraction. The method used is innovative in two respects: we used jabberwocky materials to control for semantic influences and focus on structural agreement processing, and we used a Speed-Accuracy Trade-off (SAT) design combined with a memory probe recognition task, as classically used in list memorization tasks. SAT allowed us to investigate the full time-course of processing and it enabled the joint measurement of retrieval speed and retrieval accuracy. Experiment 1 first established that attraction arises in jabberwocky sentences, to a similar extent and following the same structure-dependency as in natural sentences. Experiment 2 showed a close alignment between the attraction profiles found in Experiment 1 and memory parameters. Results support a content-addressable architecture of memory representations for sentences in which nouns’ accessibility depends on their syntactic position, while subjects are kept in the focus of attention.

Prefrontal Control of Familiarity and Recollection in Working Memory

Left inferior frontal gyrus (IFG) is a critical neural substrate for the resolution of proactive interference (PI) in working memory. We hypothesized that left IFG achieves this by controlling the influence of familiarity- versus recollection-based information about memory probes. Consistent with this idea, we observed evidence for an early (200 msec)-peaking signal corresponding to memory probe familiarity and a late (500 msec)-resolving signal corresponding to full accrual of trial-related contextual (“recollection-based”) information. Next, we applied brief trains of repetitive transcranial magnetic stimulation (rTMS) time locked to these mnemonic signals, to left IFG and to a control region. Only early rTMS of left IFG produced a modulation of the false alarm rate for high-PI probes. Additionally, the magnitude of this effect was predicted by individual differences in susceptibility to PI. These results suggest that left IFG-based control may bias the influence of familiarity- and recollection-based signals on recognition decisions.