The hippocampus as the switchboard between perception and memory.

Adaptive memory recall requires a rapid and flexible switch from external perceptual reminders to internal mnemonic representations. However, owing to the limited temporal or spatial resolution of brain imaging modalities used in isolation, the hippocampal-cortical dynamics supporting this process remain unknown. We thus employed an object-scene cued recall paradigm across two studies, including intracranial electroencephalography (iEEG) and high-density scalp EEG. First, a sustained increase in hippocampal high gamma power (55 to 110 Hz) emerged 500 ms after cue onset and distinguished successful vs. unsuccessful recall. This increase in gamma power for successful recall was followed by a decrease in hippocampal alpha power (8 to 12 Hz). Intriguingly, the hippocampal gamma power increase marked the moment at which extrahippocampal activation patterns shifted from perceptual cue toward mnemonic target representations. In parallel, source-localized EEG alpha power revealed that the recall signal progresses from hippocampus to posterior parietal cortex and then to medial prefrontal cortex. Together, these results identify the hippocampus as the switchboard between perception and memory and elucidate the ensuing hippocampal-cortical dynamics supporting the recall process.

Working memory dysfunction in fibromyalgia is associated with genotypes of the catechol- O-methyltransferase gene: an event-related potential study.

Recent findings have associated different COMT genotypes with working memory capacity in patients with fibromyalgia. Although it is thought that the COMT gene may influence neural correlates (P2 and P3 ERP components) underlying working memory impairment in this chronic-pain syndrome, it has not yet been explored. Therefore, the aim of the present research was to investigate the potential effect of the COMT gene in fibromyalgia patients on ERP working memory indices (P2 and P3 components). For this purpose, 102 participants (51 patients and 51 healthy control participants) took part in the experiment. Event-related potentials and behavioral responses were recorded while participants performed a spatial n-back task. Participants had to decide if the stimulus coincided or not in the same location as the one presented one (1-back condition) or two (2-back condition) trials before. Genotypes of the COMT gene were determined through a saliva sample from all participants. Present results significantly showed lower working memory performance (p < 0.05) in patients with fibromyalgia as compared to control participants (higher rate of errors and slower reaction times). At neural level, we found that patients exhibited enhanced frontocentral and parieto-occipital P2 amplitudes compared to control participants (p < 0.05). Interestingly, we also observed that only fibromyalgia patients carrying the Val/Val genotype of the COMT gene showed higher frontocentral P2 amplitudes than control participants (p < 0.05). Current results (behavioral outcomes and P2 amplitudes) confirmed the presence of an alteration in working memory functioning in fibromyalgia. The enhancement of frontocentral P2 could be reflecting that these patients would manifest an inefficient way of activating executive attention processes, in carriers of the Val/Val genotype of COMT. To our knowledge, the present findings are the first linking neural indices of working memory dysfunctions and COMT genotypes in fibromyalgia. Applying a subgroup of patient's strategy based on this genetic marker could be useful to establish more tailored therapeutical approaches.

Pain E-motion Faces Database (PEMF): Pain-related micro-clips for emotion research.

A large number of publications have focused on the study of pain expressions. Despite the growing knowledge, the availability of pain-related face databases is still very scarce compared with other emotional facial expressions. The Pain E-Motion Faces Database (PEMF) is a new open-access database currently consisting of 272 micro-clips of 68 different identities. Each model displays one neutral expression and three pain-related facial expressions: posed, spontaneous-algometer and spontaneous-CO2 laser. Normative ratings of pain intensity, valence and arousal were provided by students of three different European universities. Six independent coders carried out a coding process on the facial stimuli based on the Facial Action Coding System (FACS), in which ratings of intensity of pain, valence and arousal were computed for each type of facial expression. Gender and age effects of models across each type of micro-clip were also analysed. Additionally, participants' ability to discriminate the veracity of pain-related facial expressions (i.e., spontaneous vs posed) was explored. Finally, a series of ANOVAs were carried out to test the presence of other basic emotions and common facial action unit (AU) patterns. The main results revealed that posed facial expressions received higher ratings of pain intensity, more negative valence and higher arousal compared with spontaneous pain-related and neutral faces. No differential effects of model gender were found. Participants were unable to accurately discriminate whether a given pain-related face represented spontaneous or posed pain. PEMF thus constitutes a large open-source and reliable set of dynamic pain expressions useful for designing experimental studies focused on pain processes.

Alpha Rhythms Reveal When and Where Item and Associative Memories Are Retrieved.

Memories for past experiences can range from vague recognition to full-blown recall of associated details. Electroencephalography has shown that recall signals unfold a few hundred milliseconds after simple recognition, but has only provided limited insights into the underlying brain networks. Functional magnetic resonance imaging (fMRI) has revealed a "core recollection network" (CRN) centered on posterior parietal and medial temporal lobe regions, but the temporal dynamics of these regions during retrieval remain largely unknown. Here we used Magnetoencephalography in a memory paradigm assessing correct rejection (CR) of lures, item recognition (IR) and associative recall (AR) in human participants of both sexes. We found that power decreases in the alpha frequency band (10-12 Hz) systematically track different mnemonic outcomes in both time and space: Over left posterior sensors, alpha power decreased in a stepwise fashion from 500 ms onward, first from CR to IR and then from IR to AR. When projecting alpha power into source space, the CRN known from fMRI studies emerged, including posterior parietal cortex (PPC) and hippocampus. While PPC showed a monotonic change across conditions, hippocampal effects were specific to recall. These region-specific effects were corroborated by a separate fMRI dataset. Importantly, alpha power time courses revealed a temporal dissociation between item and associative memory in hippocampus and PPC, with earlier AR effects in hippocampus. Our data thus link engagement of the CRN to the temporal dynamics of episodic memory and highlight the role of alpha rhythms in revealing when and where different types of memories are retrieved.SIGNIFICANCE STATEMENT Our ability to remember ranges from the vague feeling of familiarity to vivid recollection of associated details. Scientific understanding of episodic memory thus far relied upon separate lines of research focusing on either temporal (via electroencephalography) or spatial (via functional magnetic resonance imaging) dimensions. However, both techniques have limitations that have hindered understanding of when and where memories are retrieved. Capitalizing on the enhanced temporal and spatial resolution of magnetoencephalography, we show that changes in alpha power reveal both when and where different types of memory are retrieved. Having access to the temporal and spatial characteristics of successful retrieval provided new insights into the cross-regional dynamics in the hippocampus and parietal cortex.

Disentangling neocortical alpha/beta and hippocampal theta/gamma oscillations in human episodic memory formation.

To form an episodic memory, we must first process a vast amount of sensory information about the to-be-encoded event and then bind these sensory representations together to form a coherent memory trace. While these two cognitive capabilities are thought to have two distinct neural origins, with neocortical alpha/beta oscillations supporting information representation and hippocampal theta-gamma phase-amplitude coupling supporting mnemonic binding, evidence for a dissociation between these two neural markers is conspicuously absent. To address this, seventeen human participants completed an associative memory task that first involved processing information about three sequentially-presented stimuli, and then binding these stimuli together into a coherent memory trace, all the while undergoing MEG recordings. We found that decreases in neocortical alpha/beta power during sequence perception, but not mnemonic binding, correlated with enhanced memory performance. Hippocampal theta/gamma phase-amplitude coupling, however, showed the opposite pattern; increases during mnemonic binding (but not sequence perception) correlated with enhanced memory performance. These results demonstrate that memory-related decreases in neocortical alpha/beta power and memory-related increases in hippocampal theta/gamma phase-amplitude coupling arise at distinct stages of the memory formation process. We speculate that this temporal dissociation reflects a functional dissociation in which neocortical alpha/beta oscillations could support the processing of incoming information relevant to the memory, while hippocampal theta-gamma phase-amplitude coupling could support the binding of this information into a coherent memory trace.

Test-retest reliability of resting-state magnetoencephalography power in sensor and source space.

Several studies have reported changes in spontaneous brain rhythms that could be used as clinical biomarkers or in the evaluation of neuropsychological and drug treatments in longitudinal studies using magnetoencephalography (MEG). There is an increasing necessity to use these measures in early diagnosis and pathology progression; however, there is a lack of studies addressing how reliable they are. Here, we provide the first test-retest reliability estimate of MEG power in resting-state at sensor and source space. In this study, we recorded 3 sessions of resting-state MEG activity from 24 healthy subjects with an interval of a week between each session. Power values were estimated at sensor and source space with beamforming for classical frequency bands: delta (2-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), low beta (13-20 Hz), high beta (20-30 Hz), and gamma (30-45 Hz). Then, test-retest reliability was evaluated using the intraclass correlation coefficient (ICC). We also evaluated the relation between source power and the within-subject variability. In general, ICC of theta, alpha, and low beta power was fairly high (ICC > 0.6) while in delta and gamma power was lower. In source space, fronto-posterior alpha, frontal beta, and medial temporal theta showed the most reliable profiles. Signal-to-noise ratio could be partially responsible for reliability as low signal intensity resulted in high within-subject variability, but also the inherent nature of some brain rhythms in resting-state might be driving these reliability patterns. In conclusion, our results described the reliability of MEG power estimates in each frequency band, which could be considered in disease characterization or clinical trials.

Long-term findings on working memory neural dynamics in healthcare workers after mild COVID-19.

OBJECTIVE: Understanding the long-term impact of Coronavirus Disease 2019 (COVID-19) on cognitive function, even in mild cases, is critical to the well-being of individuals, especially for healthcare workers who are at increased risk of exposure to the virus. To the best of our knowledge, the electrophysiological activity underlying cognitive functioning has not yet been explored. METHODS: Seventy-seven healthcare workers took part in the study (43 with mild infection about one year before the study and 34 uninfected). To assess cognitive status, event-related potentials (ERPs) and behavioural responses were recorded while participants performed a working memory task. RESULTS: COVID-19 participants exhibited a distinct neural pattern with lower parieto-occipital N1 amplitudes and higher frontal P2 amplitudes as compared to non-infected healthcare workers. We found no behavioural differences (reaction times and error rates) in working memory functioning between groups. CONCLUSIONS: This neural pattern suggests the presence of a decrement of processing resources linked to the encoding of sensory information (N1), followed by the enhanced of the P2 response which could be interpreted as the activation of compensation mechanism in COVID-19 participants. SIGNIFICANCE: The current findings point out that ERPs could serve as valuable neural indices for detecting distinctive patterns in working memory functioning of COVID-19 participants, even in mild cases. However, further research is required to precisely ascertain the long-term cognitive effects of COVID-19 beyond one-year post-infection.

Neural correlates of the attentional bias towards pain-related faces in fibromyalgia patients: An ERP study using a dot-probe task.

BACKGROUND: One of the major cognitive deficits in fibromyalgia has been linked to the hypervigilance phenomenon. It is mainly reflected as a negative bias for allocating attentional resources towards both threatening and pain-related information. Although the interest in its study has recently grown, the neural temporal dynamics of the attentional bias in fibromyalgia still remains an open question. METHOD: Fifty participants (25 fibromyalgia patients and 25 healthy control subjects) performed a dot-probe task. Two types of facial expressions (pain-related and neutral) were employed as signal stimuli. Then, as a target stimulus, a single dot replaced the location of one of these two faces. Event-related potentials (ERP) in response to facial expressions and target stimulation (i.e., dot) were recorded. Reaction time (RT) and accuracy measures in the experimental task were collected as behavioural outcomes. RESULTS: Temporal dynamics of brain electrical activity were analysed on two ERP components (P2 and N2a) sensitive to the facial expressions meaning. Pain-related faces elicited higher frontal P2 amplitudes than neutral faces for the whole sample. Interestingly, an interaction effect between group and facial expressions was also found showing that pain-related faces elicited enhanced P2 amplitudes (at fronto-central regions, in this case) compared to neutral faces only when the group of patients was considered. Furthermore, higher P2 amplitudes were observed in response to pain-related faces in patients with fibromyalgia compared to healthy control participants. Additionally, a shorter latency of P2 (at centro-parietal regions) was also detected for pain-related facial expressions compared to neutral faces. Regarding the amplitude of N2a, it was lower for patients as compared to the control group. Non-relevant effects of the target stimulation on the ERPs were found. However, patients with fibromyalgia exhibited slower RT to locate the single dot for incongruent trials as compared to congruent and neutral trials. CONCLUSIONS: Data suggest the presence of an attentional bias in fibromyalgia that it would be followed by a deficit in the allocation of attentional resources to further process pain-related information. Altogether the current results suggest that attentional biases in fibromyalgia might be explained by automatic attentional mechanisms, which seem to be accompanied by an alteration of more strategic or controlled attentional components.

Alpha/beta power decreases during episodic memory formation predict the magnitude of alpha/beta power decreases during subsequent retrieval.

Episodic memory retrieval is characterised by the vivid reinstatement of information about a personally-experienced event. Growing evidence suggests that this reinstatement is supported by reductions in the spectral power of alpha/beta activity. Given that the amount of information that can be recalled depends on the amount of information that was originally encoded, information-based accounts of alpha/beta activity would suggest that retrieval-related alpha/beta power decreases similarly depend upon decreases in alpha/beta power during encoding. To test this hypothesis, seventeen human participants completed a sequence-learning task while undergoing concurrent MEG recordings. Regression-based analyses were then used to estimate how alpha/beta power decreases during encoding predicted alpha/beta power decreases during retrieval on a trial-by-trial basis. When subjecting these parameter estimates to group-level analysis, we find evidence to suggest that retrieval-related alpha/beta (7-15Hz) power decreases fluctuate as a function of encoding-related alpha/beta power decreases. These results suggest that retrieval-related alpha/beta power decreases are contingent on the decrease in alpha/beta power that arose during encoding. Subsequent analysis uncovered no evidence to suggest that these alpha/beta power decreases reflect stimulus identity, indicating that the contingency between encoding- and retrieval-related alpha/beta power reflects the reinstatement of a neurophysiological operation, rather than neural representation, during episodic memory retrieval.

Functional Connectivity Disruption in Subjective Cognitive Decline and Mild Cognitive Impairment: A Common Pattern of Alterations.

Functional connectivity (FC) alterations represent a key feature in Alzheimer's Disease (AD) and provide a useful tool to characterize and predict the course of the disease. Those alterations have been also described in Mild Cognitive Impairment (MCI), a prodromal stage of AD. There is a growing interest in detecting AD pathology in the brain in the very early stages of the disorder. Subjective Cognitive Decline (SCD) could represent a preclinical asymptomatic stage of AD but very little is known about this population. In the present work we assessed whether FC disruptions are already present in this stage, and if they share any spatial distribution properties with MCI alterations (a condition known to be highly related to AD). To this end, we measured electromagnetic spontaneous activity with MEG in 39 healthy control elders, 41 elders with SCD and 51 MCI patients. The results showed FC alterations in both SCD and MCI compared to the healthy control group. Interestingly, both groups exhibited a very similar spatial pattern of altered links: a hyper-synchronized anterior network and a posterior network characterized by a decrease in FC. This decrease was more pronounced in the MCI group. These results highlight that elders with SCD present FC alterations. More importantly, those disruptions affected AD typically related areas and showed great overlap with the alterations exhibited by MCI patients. These results support the consideration of SCD as a preclinical stage of AD and may indicate that FC alterations appear very early in the course of the disease.

Quantifying the Test-Retest Reliability of Magnetoencephalography Resting-State Functional Connectivity.

The coordinated activity of the resting-state brain can be evaluated with magnetoencephalography (MEG) for distinct brain rhythms by performing source reconstruction to estimate the activities of target brain regions and employing one of the many existent functional connectivity (FC) algorithms. Although this procedure has been applied in a great amount of studies both with healthy and pathological populations, the reliability of such FC estimates is unknown, and this impairs the use of resting-state MEG FC at the individual level. In this study, the test-retest reliability of MEG resting FC was evaluated by exploring both within- and between-subject variability in FC in 16 healthy subjects who underwent three resting-state MEG scans. FC was computed after beamforming source reconstruction with four popular FC metrics: phase-locking value (PLV), phase lag index (PLI), direct envelope correlation (d-ecor), and envelope correlation with leakage correction (lc-ecor). Then, test-restest reliability and within- and between-subject agreement were evaluated with the intraclass correlation coefficient (ICC) and Kendall's W, respectively. Reliability was found to depend on the FC metric, the frequency band, and the specific link. As a general trend, greater test-retest reliability was found for PLV in theta to gamma, and for lc-ecor and d-ecor in beta. Further inspection of the ICC distribution revealed that volume conduction effects could be contributing to high ICC in PLV and d-ecor. In addition, stronger links were found to be more reliable. Overall, this encourages the further use of resting-state MEG FC for individual-level studies, especially with PLV or envelope correlation metrics.