Concept and location neurons in the human brain provide the 'what' and 'where' in memory formation.

Our brains create new memories by capturing the 'who/what', 'where' and 'when' of everyday experiences. On a neuronal level, mechanisms facilitating a successful transfer into episodic memory are still unclear. We investigated this by measuring single neuron activity in the human medial temporal lobe during encoding of item-location associations. While previous research has found predictive effects in population activity in human MTL structures, we could attribute such effects to two specialized sub-groups of neurons: concept cells in the hippocampus, amygdala and entorhinal cortex (EC), and a second group of parahippocampal location-selective neurons. In both item- and location-selective populations, firing rates were significantly higher during successfully encoded trials. These findings are in line with theories of hippocampal indexing, since selective index neurons may act as pointers to neocortical representations. Overall, activation of distinct populations of neurons could directly support the connection of the 'what' and 'where' of episodic memory.

Side effects of monaural beat stimulation during sustained mental work on mind wandering and performance measures.

Excessive mind wandering (MW) contributes to the development and maintenance of psychiatric disorders. Previous studies have suggested that auditory beat stimulation may represent a method enabling a reduction of MW. However, little is known about how different auditory stimulation conditions are subjectively perceived and whether this perception is in turn related to changes in subjective states, behavioral measures of attention and MW. In the present study, we therefore investigated MW under auditory beat stimulation and control conditions using experience sampling during a sustained attention to response task (SART). The subjective perception of the stimulation conditions, as well as changes in anxiety, stress and negative mood after versus before stimulation were assessed via visual-analog scales. Results showed that any auditory stimulation applied during the SART was perceived as more distracting, disturbing, uncomfortable and tiring than silence and was related to more pronounced increases of stress and negative mood. Importantly, the perception of the auditory conditions as disturbing was directly correlated with MW propensity. Additionally, distracting, disturbing and uncomfortable perceptions predicted negative mood. In turn, negative mood was inversely correlated with response accuracy for target stimuli, a behavioral indicator of MW. In summary, our data show that MW and attentional performance are affected by the adverse perception of auditory stimulation, and that this influence may be mediated by changes in mood.

Modulating prospective memory and attentional control with high-definition transcranial current stimulation: Study protocol of a randomized, double-blind, and sham-controlled trial in healthy older adults.

The ability to remember future intentions (i.e., prospective memory) is influenced by attentional control. At the neuronal level, frontal and parietal brain regions have been related to attentional control and prospective memory. It is debated, however, whether more or less activity in these regions is beneficial for older adults' performance. We will test that by systematically enhancing or inhibiting activity in these regions with anodal or cathodal high-definition transcranial direct current stimulation in older adults. We will include n = 105 healthy older volunteers (60-75 years of age) in a randomized, double-blind, sham-controlled, and parallel-group design. The participants will receive either cathodal, anodal, or sham high-definition transcranial direct current stimulation of the left or right inferior frontal gyrus, or the right superior parietal gyrus (1mA for 20 min). During and after stimulation, the participants will complete tasks of attentional control and prospective memory. The results of this study will clarify how frontal and parietal brain regions contribute to attentional control and prospective memory in older healthy adults. In addition, we will elucidate the relationship between attentional control and prospective memory in that age group. The study has been registered with ClinicalTrials.gov on the 12th of May 2021 (trial identifier: NCT04882527).

Single-neuron mechanisms of neural adaptation in the human temporal lobe.

A central function of the human brain is to adapt to new situations based on past experience. Adaptation is reflected behaviorally by shorter reaction times to repeating or similar stimuli, and neurophysiologically by reduced neural activity in bulk-tissue measurements with fMRI or EEG. Several potential single-neuron mechanisms have been hypothesized to cause this reduction of activity at the macroscopic level. We here explore these mechanisms using an adaptation paradigm with visual stimuli bearing abstract semantic similarity. We recorded intracranial EEG (iEEG) simultaneously with spiking activity of single neurons in the medial temporal lobes of 25 neurosurgical patients. Recording from 4917 single neurons, we demonstrate that reduced event-related potentials in the macroscopic iEEG signal are associated with a sharpening of single-neuron tuning curves in the amygdala, but with an overall reduction of single-neuron activity in the hippocampus, entorhinal cortex, and parahippocampal cortex, consistent with fatiguing in these areas.

A key role of the hippocampal P3 in the attentional blink.

The attentional blink (AB) refers to an impaired identification of target stimuli (T2), which are presented shortly after a prior target (T1) within a rapid serial visual presentation (RSVP) stream. It has been suggested that the AB is related to a failed transfer of T2 into working memory and that hippocampus (HC) and entorhinal cortex (EC) are regions crucial for this transfer. Since the event-related P3 component has been linked to inhibitory processes, we hypothesized that the hippocampal P3 elicited by T1 may impact on T2 processing within HC and EC. To test this hypothesis, we reanalyzed microwire data from 21 patients, who performed an RSVP task, during intracranial recordings for epilepsy surgery assessment (Reber et al., 2017). We identified T1-related hippocampal P3 components in the local field potentials (LFPs) and determined the temporal onset of T2 processing in HC/EC based on single-unit response onset activity. In accordance with our hypothesis, T1-related single-trial P3 amplitudes at the onset of T2 processing were clearly larger for unseen compared to seen T2-stimuli. Moreover, increased T1-related single-trial P3 peak latencies were found for T2[unseen] versus T2[seen] trials in case of lags 1 to 3, which was in line with our predictions. In conclusion, our findings support inhibition models of the AB and indicate that the hippocampal P3 elicited by T1 plays a central role in the AB.

A Meta-Analysis on Mobile-Assisted Language Learning Applications: Benefits and Risks.

Mobile language learning applications are a pervasive facet of modern life, however evidence on their effectiveness on L2 learning outcomes is lacking. In the current work, we sought to determine the effect of mobile language learning applications on L2 proficiency between groups who used mobile language learning applications and control groups who learned with traditional methods on L2 achievement. We systematically searched journal articles and grey literature between 2007-2019 and performed a quantitative meta-analysis based on 23 synthesized effect sizes. We also performed risk of bias and quality of evidence assessments on our included papers. We found a moderate-to-strong overall effect (g = 0.88) of learning achievement using mobile language applications compared to control groups who learned with traditional approaches. At the same time, we found high risk of bias and low quality of evidence across all included studies. Our results provide evidence for mobile applications as a beneficial tool for second language learning. However, findings should be treated with caution due to risks of high bias and low quality of evidence. Improvements for future studies are discussed.

Modulation of Mind Wandering Using Monaural Beat Stimulation in Subjects With High Trait-Level Mind Wandering.

Mind wandering (MW) refers to a state when attention shifts from the task at hand or current situation toward thoughts, feelings, and imaginations. This state is often accompanied by a decline in mood, and patients suffering from major depression exhibit more perseverative MW. Hence, although the directionality of the relationship between mood and MW is still under investigation, it may be useful to explore possible avenues to reduce MW. In an earlier pilot study, we investigated MW during auditory beat stimulation in healthy subjects using thought-probes during a sustained attention to response task (SART). We found evidence for reduced MW during monaural 5 Hz beats compared to silence, sine tones, and binaural 5 Hz beats. Moreover, the data tentatively suggested that this reduction was particularly pronounced in subjects with high levels of MW during silence. In the current study, we therefore asked whether MW can be reduced by monaural theta beats in subjects with high trait-levels of MW, as indicated by an online MW questionnaire. Preselected subjects performed a SART task with thought-probes assessing the propensity to mind wander, meta-awareness, and the temporal orientation of MW. Stimulation conditions comprised monaural theta beats, as well as silence (headphones on), and sine tones as control conditions. Our main hypothesis stating that the propensity to mind wander during monaural theta beats is reduced compared to both control conditions was only partly confirmed. Indeed, MW was significantly diminished during exposure to the theta beats compared to sine tones. However, reduced MW during theta beats versus silence was only observed in a subgroup using stricter inclusion criteria. Considering possible reasons for this outcome, our data suggest that the preselection procedure was suboptimal and that beat effects are modulated by the individual responses to auditory stimulation in general.

On the relationship between mind wandering and mindfulness.

Mind wandering (MW) and mindfulness have both been reported to be vital moderators of psychological wellbeing. Here, we aim to examine how closely associated these phenomena are and evaluate the psychometrics of measures often used to quantify them. We investigated two samples, one consisting of German-speaking unpaid participants (GUP, n [Formula: see text] 313) and one of English-speaking paid participants (EPP, n [Formula: see text] 228) recruited through MTurk.com. In an online experiment, we collected data using the Mindful Attention Awareness Scale (MAAS) and the sustained attention to response task (SART) during which self-reports of MW and meta-awareness of MW were recorded using experience sampling (ES) probes. Internal consistency of the MAAS was high (Cronbachs [Formula: see text] of 0.96 in EPP and 0.88 in GUP). Split-half reliability for SART measures and self-reported MW was overall good with the exception of SART measures focusing on Nogo trials, and those restricted to SART trials preceding ES in a 10 s time window. We found a moderate negative association between trait mindfulness and MW as measured with ES probes in GUP, but not in EPP. Our results suggest that MW and mindfulness are on opposite sides of a spectrum of how attention is focused on the present moment and the task at hand.

Standardized database of 400 complex abstract fractals.

In experimental settings, characteristics of presented stimuli influence cognitive processes. Knowledge about stimulus features is important to manipulate or control the influence of stimuli. To date, there are a lack of standardized data incorporating such information for complex abstract stimuli. Thus, we provide norms for a database of 400 abstract and complex stimuli. Grey-scaled fractals were rated by 512 participants on the stimulus features of abstractness, animacy, verbalizability, complexity, familiarity, favorableness, and memorability. Moreover, 111 participants labeled the fractals, enabling us to calculate indices of naming agreement and modal names. Overall, the results confirmed high abstractness and low verbalizability of the provided stimuli. To establish external validation for selected stimulus features, we evaluated (a) classifier probability of a deep neural network labeling the fractals, negatively correlated with ratings of abstractness and positively with verbalizability and naming agreement; (b) data compression rate of fractal image files, positively correlated with the rating of complexity; and (c) performance of 212 participants in a recognition-memory task, positively correlated with the rating of memorability. The present work fills the gap of a standardized database for abstract stimuli and provides a database with valid norms for abstract and complex stimuli based on ratings and external validation measures. This database can be used to control and manipulate these stimulus features in experimental settings using abstract stimuli. Such a database is essential in experimental research using abstract stimuli for instance to control for verbal influence and strategy or to control for novelty and familiarity.

Spacing, Feedback, and Testing Boost Vocabulary Learning in a Web Application.

Information and communication technology (ICT) becomes more prevalent in education but its general efficacy and that of specific learning applications are not fully established yet. One way to further improve learning applications could be to use insights from fundamental memory research. We here assess whether four established learning principles (spacing, corrective feedback, testing, and multimodality) can be translated into an applied ICT context to facilitate vocabulary learning in a self-developed web application. Effects on the amount of newly learned vocabulary were assessed in a mixed factorial design (3×2×2×2) with the independent variables Spacing (between-subjects; one, two, or four sessions), Feedback (within-subjects; with or without), Testing (within-subjects, 70 or 30% retrieval trials), and Multimodality (within-subjects; unimodal or multimodal). Data from 79 participants revealed significant main effects for Spacing [F(2,76) = 8.51, p = 0.0005, η p 2 = 0.18 ] and Feedback [F(1,76) = 21.38, p < 0.0001, η p 2 = 0.22 ], and a significant interaction between Feedback and Testing [F(1,76) = 14.12, p = 0.0003, η p 2 = 0.16 ]. Optimal Spacing and the presence of corrective Feedback in combination with Testing together boost learning by 29% as compared to non-optimal realizations (massed learning, testing with the lack of corrective feedback). Our findings indicate that established learning principles derived from basic memory research can successfully be implemented in web applications to optimize vocabulary learning.

Concept neurons in the human medial temporal lobe flexibly represent abstract relations between concepts.

Concept neurons in the medial temporal lobe respond to semantic features of presented stimuli. Analyzing 61 concept neurons recorded from twelve patients who underwent surgery to treat epilepsy, we show that firing patterns of concept neurons encode relations between concepts during a picture comparison task. Thirty-three of these responded to non-preferred stimuli with a delayed but well-defined onset whenever the task required a comparison to a response-eliciting concept, but not otherwise. Supporting recent theories of working memory, concept neurons increased firing whenever attention was directed towards this concept and could be reactivated after complete activity silence. Population cross-correlations of pairs of concept neurons exhibited order-dependent asymmetric peaks specifically when their response-eliciting concepts were to be compared. Our data are consistent with synaptic mechanisms that support reinstatement of concepts and their relations after activity silence, flexibly induced through task-specific sequential activation. This way arbitrary contents of experience could become interconnected in both working and long-term memory.

Auditory Beat Stimulation Modulates Memory-Related Single-Neuron Activity in the Human Medial Temporal Lobe.

Auditory beats are amplitude-modulated signals (monaural beats) or signals that subjectively cause the perception of an amplitude modulation (binaural beats). We investigated the effects of monaural and binaural 5 Hz beat stimulation on neural activity and memory performance in neurosurgical patients performing an associative recognition task. Previously, we had reported that these beat stimulation conditions modulated memory performance in opposite directions. Here, we analyzed data from a patient subgroup, in which microwires were implanted in the amygdala, hippocampus, entorhinal cortex and parahippocampal cortex. We identified neurons responding with firing rate changes to binaural versus monaural 5 Hz beat stimulation. In these neurons, we correlated the differences in firing rates for binaural versus monaural beats to the memory-related differences for remembered versus forgotten items and associations. In the left hemisphere, we detected statistically significant negative correlations between firing rate differences for binaural versus monaural beats and remembered versus forgotten items/associations. Importantly, such negative correlations were also observed between beat stimulation-related firing rate differences in the pre-stimulus window and memory-related firing rate differences in the post-stimulus windows. In line with concepts of homeostatic plasticity, our findings suggest that beat stimulation is linked to memory performance via shifting baseline firing levels.

Does a smartphone on the desk drain our brain? No evidence of cognitive costs due to smartphone presence in a short-term and prospective memory task.

It has recently been shown that the mere presence of one's own smartphone on the desk impairs working memory performance. The aim of this study was to follow up on this important finding by assessing the effect of smartphone presence (present on the desk vs. absent from the desk) on different memory functions (short-term memory and prospective memory), and by further examining the moderating role of individual differences in smartphone dependency and impulsiveness. We found no overall effect of smartphone presence on short-term and prospective memory performance. There was a moderating effect for prospective memory: Performance was better when the smartphone was absent versus present for participants with low smartphone dependency. In light of the absence of an overall effect of smartphone presence on memory functions, our results show that previous findings of impairments in working memory due to smartphone presence do not generalize to other domains of memory capacity.

Correction: Representation of abstract semantic knowledge in populations of human single neurons in the medial temporal lobe.

[This corrects the article DOI: 10.1371/journal.pbio.3000290.].

Representation of abstract semantic knowledge in populations of human single neurons in the medial temporal lobe.

Sensory experience elicits complex activity patterns throughout the neocortex. Projections from the neocortex converge onto the medial temporal lobe (MTL), in which distributed neocortical firing patterns are distilled into sparse representations. The precise nature of these neuronal representations is still unknown. Here, we show that population activity patterns in the MTL are governed by high levels of semantic abstraction. We recorded human single-unit activity in the MTL (4,917 units, 25 patients) while subjects viewed 100 images grouped into 10 semantic categories of 10 exemplars each. High levels of semantic abstraction were indicated by representational similarity analyses (RSAs) of patterns elicited by individual stimuli. Moreover, pattern classifiers trained to decode semantic categories generalised successfully to unseen exemplars, and classifiers trained to decode exemplar identity more often confused exemplars of the same versus different categories. Semantic abstraction and generalisation may thus be key to efficiently distill the essence of an experience into sparse representations in the human MTL. Although semantic abstraction is efficient and may facilitate generalisation of knowledge to novel situations, it comes at the cost of a loss of detail and may be central to the generation of false memories.

TV vs. YouTube: TV Advertisements Capture More Visual Attention, Create More Positive Emotions and Have a Stronger Impact on Implicit Long-Term Memory.

In an experiment, effects of commercials that are either shown within a TV program or embedded in YouTube videos were compared. These two media environments have not yet been compared empirically in terms of their advertising impact. A within-subjects design and a multi-method approach were used (N = 36). Eye tracking data show that more attention is allocated to advertisements that appear within a TV program compared to the YouTube-condition and the viewing experience elicited more positive emotions in the TV-condition. Two days after reception, no difference in recognition, likeability, and purchase intention occurred, but in terms of implicit long-term memory: In the TV condition, brands that were previously advertised but no longer remembered elicited stronger skin conductance change than brands for which no advertisements had previously been shown. In terms of advertising impact, TV seems to still be the better choice for advertisers. Presentation mode should be considered in future evaluation of advertisement potential.

Recollection in the human hippocampal-entorhinal cell circuitry.

Imagine how flicking through your photo album and seeing a picture of a beach sunset brings back fond memories of a tasty cocktail you had that night. Computational models suggest that upon receiving a partial memory cue ('beach'), neurons in the hippocampus coordinate reinstatement of associated memories ('cocktail') in cortical target sites. Here, using human single neuron recordings, we show that hippocampal firing rates are elevated from ~ 500-1500 ms after cue onset during successful associative retrieval. Concurrently, the retrieved target object can be decoded from population spike patterns in adjacent entorhinal cortex (EC), with hippocampal firing preceding EC spikes and predicting the fidelity of EC object reinstatement. Prior to orchestrating reinstatement, a separate population of hippocampal neurons distinguishes different scene cues (buildings vs. landscapes). These results elucidate the hippocampal-entorhinal circuit dynamics for memory recall and reconcile disparate views on the role of the hippocampus in scene processing vs. associative memory.

Cue discriminability predicts instrumental conditioning.

Charting mental acts that succeed or fail under unconscious instances of cognition informs debates on the nature and potential functions of consciousness. A prominent method to exclude conscious contributions to cognition is to render visual stimuli unconscious by short and pattern-masked presentations. Here, we explore a combination of visual masking and pixel noise added to visual stimuli as a method to adapt discriminability in a fine-grained fashion to subject- and stimulus-specific estimates of perceptual thresholds. Estimates of the amount of pixel noise corresponding to perceptual thresholds are achieved by psychometric adaptive algorithms in an identification task. Afterwards, the feasibility of instrumental conditioning is tested at four levels of cue discriminability relative to previously acquired estimates of perceptual thresholds. In contrast to previous reports (Pessiglione et al., 2008), no evidence for the feasibility of instrumental condition was gathered when contributions of conscious cognition were excluded.

Mind wandering simultaneously prolongs reactions and promotes creative incubation.

Mind wandering (MW) refers to the disengagement of attention from the external environment and the generation of thoughts unrelated to the task at hand. It is a ubiquitous cognitive process resulting in lapses of attention. MW imposes a negative impact on attention-based task performance, but also has been associated with enhanced creativity and future planning. In three experiments we show that MW relates simultaneously to both behavioral costs but also benefits. Behavioral costs were measured by prolonged reaction times (RT) in sustained attention to response tasks (SART), whereas the benefits were observed as improved performance in the creative problem solving and daily routine planning tasks performed after the SART. Additionally, we found an increased dispersion of RTs during MW suggesting that attention during these times underwent dynamical changes compared to states when participants were fully focused on the task. Our results support a model in which MW deteriorates performance in the task at hand and is related to dynamical changes in attention. At the same time it is also able to improve human capacity for complex operations.

Single-Neuron Correlates of Conscious Perception in the Human Medial Temporal Lobe.

The neuronal mechanisms giving rise to conscious perception remain largely elusive [1]. It is known that the strength of single-neuron activity correlates with conscious perception, especially in anterior regions of the ventral pathway in non-human primates [2-4] and in the human medial temporal lobe (MTL) [5, 6]. It is unclear, however, whether single-neuron correlates of conscious perception are characterized solely by the magnitude of neuronal responses, and whether the correlates of perception are equally prominent across different regions of the human MTL. While recording from 2,735 neurons in 21 neurosurgical patients during 40 experimental sessions, we created experimental conditions in which otherwise identical visual stimuli are sometimes seen and sometimes not detected at all by means of the attentional blink, i.e., the phenomenon that the second of two target stimuli in close succession often goes unnoticed to conscious perception [7]. Remarkably, responses to unseen versus seen stimuli were delayed and temporally more dispersed, in addition to being attenuated in firing rate. This finding suggests precise timing of neuronal responses as a novel candidate physiological marker of conscious perception. In addition, we found modulation of neuronal response timing and strength in response to seen versus unseen stimuli to increase along an anatomical gradient from the posterior to the anterior MTL. Our results thus map out the neuronal correlates of conscious perception in the human MTL both in time and in space.