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Astronauts on interplanetary missions - such as to Mars - will be exposed to space radiation, a spectrum of highly-charged, fast-moving particles that includes 56 Fe and 28 Si. Earth-based preclinical studies show space radiation decreases rodent performance in low- and some high-level cognitive tasks. Given astronaut use of touchscreen platforms during training and space flight and given the ability of rodent touchscreen tasks to assess functional integrity of brain circuits and multiple cognitive domains in a non-aversive way, here we exposed 6-month-old C57BL/6J male mice to whole-body space radiation and subsequently assessed them on a touchscreen battery. Relative to Sham treatment, 56 Fe irradiation did not overtly change performance on tasks of visual discrimination, reversal learning, rule-based, or object-spatial paired associates learning, suggesting preserved functional integrity of supporting brain circuits. Surprisingly, 56 Fe irradiation improved performance on a dentate gyrus-reliant pattern separation task; irradiated mice learned faster and were more accurate than controls. Improved pattern separation performance did not appear to be touchscreen-, radiation particle-, or neurogenesis-dependent, as 56 Fe and 28 Si irradiation led to faster context discrimination in a non-touchscreen task and 56 Fe decreased new dentate gyrus neurons relative to Sham. These data urge revisitation of the broadly-held view that space radiation is detrimental to cognition.

Background/Aims: AL-108-211 was a placebo-controlled, ascending-dose study that explored the safety, tolerability and efficacy of 12 weeks of treatment with AL-108 in subjects with amnestic mild cognitive impairment. Methods: A total of 144 subjects were randomized in a 2:1 drug:placebo ratio. Subjects were enrolled into the low-dose group or placebo and then to the high-dose group or placebo. Pooling of the placebo groups yielded 3 groups (approx. 48/group) whose baseline demographics and disease characteristics were well matched. Results: AL-108 was generally safe and well tolerated. Analyses of efficacy data failed to detect a statistically significant difference between the treatment groups on the composite cognitive memory score. Analyses of the individual cognitive tasks identified signals of potential efficacy in 2 tests of memory and attention. Conclusion: These data suggest that AL-108 was generally safe, well tolerated and merits additional investigation as a treatment for Alzheimer's disease.

Rationale Use of cross-species neuropsychological paradigms such as visual–spatial paired associate learning (PAL) may allow for a better understanding of underlying neural substrates of memory. Such paradigms, which are often used to guide models of memory in animals, can then be carried forward into humans to provide a basis for evaluation of pharmacologic compounds designed to ameliorate learning and memory impairments in neurologic and psychiatric morbidities. Objectives This double-blind, randomized, crossover trial investigated effects of donepezil, an acetylcholinesterase (AChE) inhibitor, in attenuating scopolamine-induced cognitive impairment using a novel, “process-based” computerized measure of visual–spatial PAL. Results In healthy male volunteers, scopolamine (0.6 mg) induced a time-dependent reduction in visual–spatial PAL, with the greatest impairment (Cohen's d  = 1.37) observed 2 h after dosing. Cotreatment with donepezil (10 mg) significantly ameliorated scopolamine-induced impairment at the 2-h time point (Cohen's d  = 0.66). Process-based analyses revealed a significant impairment in both memory (Cohen's d  = 1.37 to 0.50) and executive (Cohen's d  = 1 .21 to 0.62) aspects of visual–spatial PAL performance following acute scopolamine challenge, and these reductions were ameliorated by donepezil. Conclusions Acute scopolamine challenge can produce large and robust deficits in visual–spatial PAL, which reflect impairments in both memory and executive processes. Coadministration of a single dose of donepezil can ameliorate these deficits. These results provide support for the use of a visual–spatial PAL test as a pharmacodynamic cognitive marker of central nervous system (CNS)-mediating compounds in humans.

Rationale Patients with obsessive compulsive disorder (OCD) demonstrate impaired cognition in some selected domains. Although serotoninergic dysfunction has been implicated in OCD, recent evidence suggests that dopamine may play a role as well. Objective The aim of the study was to evaluate learning and working memory in OCD and to determine the effects of dopaminergic manipulations on these capacities. Methods Visuospatial associative memory and spatial and verbal working memory were examined in 18 nondepressed patients with OCD and 18 matched healthy controls. The study further investigated whether acute administration of dopamine D2/D3 receptor agonist and antagonist would differentially modulate cognition in OCD. Each participant underwent the cognitive battery three times in a randomized double-blind, placebo-controlled crossover design. Results Significant impairments in patients compared with controls were noted on the Cambridge Neuropsychological Test Automated Battery (CANTAB) paired associates learning (PAL) and a measure of sustained attention (rapid visual information processing, RVIP) that persisted across all sessions, with deficient strategy in the CANTAB spatial working memory task in the first session alone. Although the dopamine D2/D3 agonist, pramipexole, led to poorer performance on the PAL and RVIP tasks, no differential effects were noted between the two groups. No significant effects were noted for the D2/D3 antagonist, amisulpride. Conclusions The results are consistent with a specific associative memory deficit in OCD that remained robust despite possible practice effects and compensatory strategies and point to abnormal medial temporal lobe involvement in OCD in addition to the previously implicated frontostriatal loops, with no clear evidence of D2 receptor mediation.

Here, we view the mental lexicon as a semantic network where words are connected if they are semantically related. Steyvers and Tenenbaum ( Cognitive Science, 29 , 41–78, 2005 ) proposed that the growth of semantic networks follows preferential attachment , the observation that new nodes are more likely to connect to preexisting nodes that are more well connected (i.e., the rich get richer). If this is the case, well-connected known words should be better at acquiring new links than poorly connected words. We tested this prediction in three paired-associate learning (PAL) experiments in which participants memorized arbitrary cue–response word pairs. We manipulated the semantic connectivity of the cue words, indexed by the words’ free associative degree centrality. Experiment 1 is a reanalysis of the PAL data from Qiu and Johns ( Psychonomic Bulletin & Review , 27 , 114–121, 2020 ), in which young adults remembered 40 cue–response word pairs (e.g., nature – chain ) and completed a cued recall task. Experiment 2 is a preregistered replication of Qiu and Johns. Experiment 3 addressed some limitations in Qiu and Johns’s design by using pseudowords as the response items (e.g., boot – arruity ). The three experiments converged to show that cue words of higher degree centrality facilitated the recall/recognition of the response items, providing support for the notion that better-connected words have a greater ability to acquire new links (i.e., the rich do get richer). Importantly, while degree centrality consistently accounted for significant portions of variance in PAL accuracy, other psycholinguistic variables (e.g., concreteness, contextual diversity) did not, suggesting that degree centrality is a distinct variable that affects the ease of verbal associative learning.

Newly acquired declarative memory traces are believed to be reactivated during NonREM sleep to promote their hippocampo-neocortical transfer for long-term storage. Yet it remains a major challenge to unravel the underlying neuronal mechanisms. Using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) recordings in humans, we show that sleep spindles play a key role in the reactivation of memory-related neocortical representations. On separate days, participants either learned face-scene associations or performed a visuomotor control task. Spindle-coupled reactivation of brain regions representing the specific task stimuli was traced during subsequent NonREM sleep with EEG-informed fMRI. Relative to the control task, learning face-scene associations triggered a stronger combined activation of neocortical and hippocampal regions during subsequent sleep. Notably, reactivation did not only occur in temporal synchrony with spindle events but was tuned by ongoing variations in spindle amplitude. These learning-related increases in spindle-coupled neocortical activity were topographically specific because reactivation was restricted to the face- and scene-selective visual cortical areas previously activated during pre-sleep learning. Spindle-coupled hippocampal activation was stronger the better the participant had performed at prior learning. These results are in agreement with the notion that sleep spindles orchestrate the reactivation of new hippocampal–neocortical memories during sleep. ► Subjects learned face-scene associations or performed a visuomotor control task. ► EEG-fMRI during subsequent NREM sleep revealed spindle-related brain activation. ► Contrasting learning and control nights revealed spindle-related reactivation. ► Reactivation was restricted to category-specific neocortical sites and hippocampus. ► Reactivation was time-locked to sleep spindles and dependent on their amplitude.

Word learning is one of the first steps into language, and vocabulary knowledge predicts reading, speaking, and writing ability. There are several pathways to word learning and little is known about how they differ. Previous research has investigated paired-associate (PAL) and cross-situational word learning (CSWL) separately, limiting the understanding of how the learning process compares across the two. In PAL, the roles of word familiarity and working memory have been thoroughly examined, but these same factors have received very little attention in CSWL. We randomly assigned 126 monolingual adults to PAL or CSWL. In each task, names of 12 novel objects were learned (six familiar words, six unfamiliar words). Logistic mixed-effects models examined whether word-learning paradigm, word type and working memory (measured with a backward digit-span task) predicted learning. Results suggest better learning performance in PAL and on familiar words. Working memory predicted word learning across paradigms, but no interactions were found between any of the predictors. This suggests that PAL is easier than CSWL, likely because of reduced ambiguity between the word and the referent, but that learning across both paradigms is equally enhanced by word familiarity, and similarly supported by working memory.

We investigated three aspects of paired associate learning of vocabulary in an unfamiliar language: monolingual-bilingual differences, effects of dominance and language proficiency, and the possible role of associative strategies. Spanish–English bilinguals (48 English-dominant and 48 Spanish-dominant) and English-speaking monolinguals (n = 48) learned Swahili–English and Swahili-Spanish word pairs. Learning was assessed using cued recall (Swahili cue or Swahili response) and associative recognition tests. English-dominant bilinguals did not outperform English monolinguals on any learning measure. Cued recall accuracy was higher when learning through the dominant language than through the non-dominant language, whether the Swahili words were cues or responses. Proficiency scores in the known language were positively correlated with cued recall accuracy, whether the cue or the response was in Swahili, indicating that proficiency effects occurred not in retrievability of known words but in learning of associations. Bilingual and monolingual participants did not differ in their reported use of associative strategies.

Rationale The CANTAB object-location paired-associate learning (PAL) test can detect cognitive deficits in schizophrenia and Alzheimer’s disease. A rodent version of touch screen PAL (dPAL) has been developed, but the underlying neural mechanisms are not fully understood. Although there is evidence that inactivation of the hippocampus following training leads to impairments in rats, this has not been tested in mice. Furthermore, it is not known whether acquisition , as opposed to performance, of the rodent version depends on the hippocampus. This is critical as many mouse models may have hippocampal dysfunction prior to the onset of task training. Objectives The objectives of this study are to examine the effects of dorsal hippocampal (dHp) dysfunction on both performance and acquisition of mouse dPAL and to determine if hippocampal task sensitivity could be increased using a newly developed context-disambiguated PAL (cdPAL) paradigm. Methods In experiment 1, C57Bl/6 mice received post-acquisition dHp infusions of the GABA agonist muscimol. In experiment 2, C57Bl/6 mice received excitotoxic dHp lesions prior to dPAL/cdPAL acquisition. Results Post-acquisition muscimol dose-dependently impaired dPAL and cdPAL performance. Pre-acquisition dHp lesions had only mild effects on both PAL tasks. Behavioural challenges including addition of objects and degradation of the visual stimuli with noise did not reveal any further impairments. Conclusions dPAL and cdPAL performance is hippocampus-dependent in the mouse, but both tasks can be learned in the absence of a functional dHp.

The formation and retention of hippocampus-dependent memories is impacted by neurogenesis, a process that involves the production of new neurons in the dentate gyrus of the hippocampus. Recent studies demonstrate that increasing neurogenesis after memory formation induces forgetting of previously acquired memories. Neurogenesis-induced forgetting was originally demonstrated in mice, but a recent report suggests that the same effect may be absent in rats. Although a general species difference is possible, other potential explanations for these incongruent findings are that memories which are more strongly reinforced become resilient to forgetting or that perhaps only certain types of memories are affected. Here, we investigated whether neurogenesis-induced forgetting occurs in rats using several hippocampus-dependent tasks including contextual fear conditioning (CFC), the Morris Water Task (MWT), and touchscreen paired associates learning (PAL). Neurogenesis was increased following training using voluntary exercise for 4 weeks before recall of the previous memory was assessed. We show that voluntary running causes forgetting of context fear memories in a neurogenesis-dependent manner, and that neurogenesis-induced forgetting is present in rats across behavioral tasks despite differences in complexity or reliance on spatial, context, or object memories. In addition, we asked whether stronger memories are less susceptible to forgetting by varying the strength of training. Even with a very strong training protocol in the CFC task, we still observed enhanced forgetting related to increased neurogenesis. These results suggest that forgetting due to neurogenesis is a conserved mechanism that aids in the clearance of memories.