Electrophysiological Signatures of Numerosity Encoding in a Delayed Match-to-Sample Task

The number of elements in a small set of items is appraised in a fast and exact manner, a phenomenon called subitizing. In contrast, humans provide imprecise responses when comparing larger numerosities, with decreasing precision as the number of elements increases. Estimation is thought to rely on a dedicated system for the approximate representation of numerosity. While previous behavioral and neuroimaging studies associate subitizing to a domain-general system related to object tracking and identification, the nature of small numerosity processing is still debated. We investigated the neural processing of numerosity across subitizing and estimation ranges by examining electrophysiological activity during the memory retention period in a delayed numerical match-to-sample task. We also assessed potential differences in the neural signature of numerical magnitude in a fully non-symbolic or cross-format comparison. In line with behavioral performance, we observed modulation of parietal-occipital neural activity as a function of numerosity that differed in two ranges, with distinctive neural signatures of small numerosities showing clear similarities with those observed in visuospatial working memory tasks. We also found differences in neural activity related to numerical information in anticipation of single vs. cross-format comparison, suggesting a top-down modulation of numerical processing. Finally, behavioral results revealed enhanced performance in the mixed-format conditions and a significant correlation between task performance and symbolic mathematical skills. Overall, we provide evidence for distinct mechanisms related to small and large numerosity and differences in numerical encoding based on task demands.

Optogenetic scrambling of hippocampal theta oscillations alters working memory retrieval but not hippocampal spatiotemporal codes

The precise temporal coordination of activity in the brain is thought to be fundamental for memory encoding and retrieval. The medial septum (MS) provides the largest source of innervation to the hippocampus (HPC), and its inhibitory neurons play a major role in controlling HPC theta (~8 Hz) oscillations. While pharmacological inhibition of the MS is associated with memory impairment, the exact role of MS inhibitory neurons in HPC function and memory is not fully understood. While HPC place cells were previously reported to not depend on MS inputs, the exact role of MS inputs on HPC temporal codes is still a matter of debate. Moreover, pharmacological manipulations do not have the temporal resolution to distinguish the role of MS activity on working memory encoding, retention and retrieval. Here we stimulated the MS with optogenetics to either pace or ablate theta, while recording large hippocampal assemblies over time using calcium imaging along with local field potentials to monitor theta control. Using scrambled light stimulation, we could robustly ablate theta signals, which was associated with direct modulation of a subpopulation of neurons in the HPC. We found that such stimulation led to decreased working memory retrieval, but not encoding in both a delayed non-match to sample task and a novel place object recognition task. Strikingly, scrambled stimulations were not associated with disrupted spatiotemporal codes. Importantly, we show that our opsin did not transfect cholinergic cells and stimulation did not disrupt HPC ripple activity or running speed, suggesting a specific role for MS GABAergic cells in memory maintenance and retrieval that is independent from these other potential confounding mechanisms. Our study suggests that theta signals play a specific and essential role in supporting working memory retrieval and maintenance while not being necessary for hippocampal spatiotemporal codes.

Prefrontal cortical contributions to working memory loading, maintenance and recall are parsed by hippocampal-prefrontal oscillatory assembly dynamics

Working memory enables incorporation of recent experience into subsequent decision-making. This processing recruits both prefrontal cortex and hippocampus, where neurons encode task cues, rules and outcomes. However, precisely which information is carried when, and by which neurons, remains unclear. Using population decoding of activity in rat medial prefrontal cortex (mPFC) and dorsal hippocampal CA1, we confirm that mPFC populations lead in maintaining sample information across delays of an operant non-match to sample task, despite individual neurons firing only transiently. During sample encoding, distinct mPFC subpopulations joined distributed CA1-mPFC cell assemblies hallmarked by 4-5Hz rhythmic modulation; CA1-mPFC assemblies re-emerged during choice episodes, but were not 4-5Hz modulated. Delay-dependent errors arose when attenuated rhythmic assembly activity heralded collapse of sustained mPFC encoding; pharmacological disruption of CA1-mPFC assembly rhythmicity impaired task performance. Our results map component processes of memory-guided decisions onto heterogeneous CA1-mPFC subpopulations and the dynamics of physiologically distinct, distributed cell assemblies.

No evidence that LSD microdosing affects recall or the balance between distracter resistance and updating

The effect of low doses (<=20 μg) of LSD on working memory, in the absence of altered states of consciousness, remain largely unexplored. Given its possible effects on serotonin 5-HT2A receptors and dopaminergic signalling, it could be hypothesised that LSD microdoses modulate working memory recall. Moreover, in line with computational models, LSD microdoses could exert antagonistic effects on distracter resistance and updating. Here, we tested this hypothesis in a randomised double-blind, placebo-controlled study comparing three different LSD microdoses (5 μg, 10μg and 20μg) with placebo. After capsule administration, participants performed a modified delay-match-to-sample (DMTS) dopamine-sensitive task. The standard DMTS task was modified to include novel items in the delay period between encoding and probe. These novel items either had to be ignored or updated into working memory. There was no evidence that LSD microdoses affected the accuracy or efficiency of working memory recall and there was no evidence for differential effects on ignoring or updating. Due to the small sample of participants, these results are preliminary and larger studies are required to establish whether LSD microdoses affect short-term recall.

The Effects of a Novel Non-catechol Dopamine Partial Agonist on Working Memory in the Aged Rhesus Monkey

Aged-related declines in cognition, especially working memory and executive function, begin in middle-age and these abilities are known to be mediated by the prefrontal cortex (PFC) and more specifically the dopamine (DA) system within the PFC. In both humans and monkeys, there is significant evidence that the PFC is the first cortical region to change with age and the PFC appears to be particularly vulnerable to age-related loss of dopamine (DA). Therefore, the DA system is a strong candidate for therapeutic intervention to slow or reverse age related declines in cognition. In the present study, we administered a novel selective, potent, non-catechol DA D1 R agonist PF-6294 (Pfizer, Inc.) to aged female rhesus monkeys and assessed their performance on two benchmark tasks of working memory – the Delayed Non-match to Sample Task (DNMS) and Delayed Recognition Span Task (DRST). The DNMS task was administered first with the standard 10 s delay and then with 5 min delays, with and without distractors. The DRST was administered each day with four trials with unique sequences and one trial of a repeated sequence to assess evidence learning and retention. Overall, there was no significant effect of drug on performance on any aspect of the DNMS task. In contrast, we demonstrated that a middle range dose of PF-6294 significantly increased memory span on the DRST on the first and last days of testing and by the last day of testing the increased memory span was driven by the performance on the repeated trials.

The capacity and cognitive processing of vibrotactile working memory for frequency

A hallmark of working memory (WM) is its limited capacity. While visual and verbal domains of WM are able to store multiple items, the capacity of parametric vibrotactile WM (vtWM) has not yet been established for supra-threshold, one-dimensional sensory vibrotactile frequencies. The present study extends the standard delayed match-to-sample vibrotactile discrimination task to determine the capacity of the vtWM and its cognitive mechanism. Here, by presenting subjects with 2 to 6 vibratory frequencies sequentially in each trial, the present study demonstrates that it is possible to retain about only two vibrotactile frequencies information in vtWM. The results also showed that the capacity of vtWM does not depend on whether sequentially presented vibrotactile frequencies are delivered to the same or to different fingers. At the same time, the rate of correct report depends on sequence length and when in the sequence the stimuli are presented, suggesting the dynamic updating of vtWM similar to that of visual WM.

Strenuous Exercise Habits and Spatial Mnemonic Discrimination Ability in Young Adult Men and Women

Increased physical activity has shown positive effects on various hippocampal memory functions through accumulating evidence that physical exercise and higher cardiorespiratory fitness can enhance human performance on nonspatial mnemonic discrimination tasks that rely on hippocampal pattern separation. However, there is less direct evidence of exercise effects on spatial pattern separation in humans, despite evidence for this association in rodent models. We examined the influence of strenuous exercise habits on spatial mnemonic discrimination among 176 young adults. We used a delayed match-/non-match-to-sample (same/different) task to assess pattern separation for spatial locations across varying degrees of similarity. Participants who reported regularly engaging in strenuous exercise three or more times per week performed significantly better than those who reported engaging in strenuous exercise fewer than three times per week, even when pattern separation tasks involved higher spatial similarity. These apparent exercise effects were observed for female, but not male, participants. These findings support likely benefits of strenuous exercise habits for human spatial pattern separation skills, and they suggest a need to explore potential interaction effects of exercise and gender.

Non-Symbolic Numerosity and Symbolic Numbers are not Processed Intuitively in Children: Evidence From an Event-Related Potential Study

The approximate number system (ANS) theory and the ANS mapping account have been the most prominent theories on non-symbolic numerosity processing and symbolic number processing respectively, over the last 20 years. Recently, there is a growing debate about these theories, mainly based on research in adults. However, whether the ANS theory and ANS mapping account explain the processing of non-symbolic numerosity and symbolic number in childhood has received little attention. In the current ERP study, we first examined whether non-symbolic numerosity processing in 9-to-12-year-old children (N = 34) is intuitive, as proposed by the ANS theory. Second, we examined whether symbolic number processing is rooted in non-symbolic numerosity processing, as proposed the ANS mapping account. ERPs were measured during four same-different match-to-sample tasks with non-symbolic numerosities, symbolic numbers, and combinations of both. We found no evidence for intuitive processing of non-symbolic numerosity. Instead, children processed the visual features of non-symbolic stimuli more automatically than the numerosity itself. Moreover, children do not seem to automatically activate non-symbolic numerosity when processing symbolic numbers. These results challenge the ANS theory and ANS mapping account in 9-to-12-year-old children.