Episodic Encoding Research Articles

Dopamine is associated with prioritization of reward-associated memories in Parkinson's disease.

Patients with Parkinson's disease have reduced reward sensitivity related to dopaminergic neuron loss, which is associated with impairments in reinforcement learning. Increasingly, however, dopamine-dependent reward signals are recognized to play an important role beyond reinforcement learning. In particular, it has been shown that reward signals mediated by dopamine help guide the prioritization of events for long-term memory consolidation. Meanwhile, studies of memory in patients with Parkinson's disease have focused on overall memory capacity rather than what is versus what isn't remembered, leaving open questions about the effect of dopamine replacement on the prioritization of memories by reward and the time-dependence of this effect. The current study sought to fill this gap by testing the effect of reward and dopamine on memory in patients with Parkinson's disease. We tested the effect of dopamine modulation and reward on two forms of long-term memory: episodic memory for neutral objects and memory for stimulus-value associations. We measured both forms of memory in a single task, adapting a standard task of reinforcement learning with incidental episodic encoding events of trial-unique objects. Objects were presented on each trial at the time of feedback, which was either rewarding or not. Memory for the trial-unique images and for the stimulus-value associations, and the influence of reward on both, was tested immediately after learning and 2 days later. We measured performance in Parkinson's disease patients tested either ON or OFF their dopaminergic medications and in healthy older control subjects. We found that dopamine was associated with a selective enhancement of memory for reward-associated images, but that it did not influence overall memory capacity. Contrary to predictions, this effect did not differ between the immediate and delayed memory tests. We also found that while dopamine had an effect on reward-modulated episodic memory, there was no effect of dopamine on memory for stimulus-value associations. Our results suggest that impaired prioritization of cognitive resource allocation may contribute to the early cognitive deficits of Parkinson's disease.

APOE4 Status is Related to Differences in Memory-Related Brain Function in Asymptomatic Older Adults with Family History of Alzheimer's Disease: Baseline Analysis of the PREVENT-AD Task Functional MRI Dataset.

Background:Episodic memory decline is one of the earliest symptoms of late-onset Alzheimer’s disease (AD). Older adults with the apolipoprotein E ɛ4 (+APOE4) genetic risk factor for AD may exhibit altered patterns of memory-related brain activity years prior to initial symptom onset.Objective:Here we report the baseline episodic memory task functional MRI results from the PRe-symptomatic EValuation of Experimental or Novel Treatments for Alzheimer’s Disease cohort in Montreal, Canada, in which 327 healthy older adults were scanned within 15 years of their parent’s conversion to AD.Methods:Volunteers were scanned as they encoded and retrieved object-location spatial source associations. The task was designed to discriminate between brain activity related to spatial source recollection and object-only (recognition) memory. We used multivariate partial least squares (PLS) to test the hypothesis that +APOE4 adults with family history of AD would exhibit altered patterns of brain activity in the recollection-related memory network, comprised of medial frontal, parietal, and medial temporal cortices, compared to APOE4 non-carriers (–APOE4). We also examined group differences in the correlation between event-related brain activity and memory performance.Results:We found group similarities in memory performance and in task-related brain activity in the recollection network, but differences in brain activity-behavior correlations in ventral occipito-temporal, medial temporal, and medial prefrontal cortices during episodic encoding.Conclusion:These findings are consistent with previous literature on the influence of APOE4 on brain activity and provide new perspective on potential gene-based differences in brain-behavior relationships in people with first-degree family history of AD.

Motor hyperactivation during cognitive tasks: An endophenotype of juvenile myoclonic epilepsy.

ObjectiveJuvenile myoclonic epilepsy (JME) is the most common genetic generalized epilepsy syndrome. Myoclonus may relate to motor system hyperexcitability and can be provoked by cognitive activities. To aid genetic mapping in complex neuropsychiatric disorders, recent research has utilized imaging intermediate phenotypes (endophenotypes). Here, we aimed to (a) characterize activation profiles of the motor system during different cognitive tasks in patients with JME and their unaffected siblings, and (b) validate those as endophenotypes of JME.MethodsThis prospective cross‐sectional investigation included 32 patients with JME, 12 unaffected siblings, and 26 controls, comparable for age, sex, handedness, language laterality, neuropsychological performance, and anxiety and depression scores. We investigated patterns of motor system activation during episodic memory encoding and verb generation functional magnetic resonance imaging (fMRI) tasks.ResultsDuring both tasks, patients and unaffected siblings showed increased activation of motor system areas compared to controls. Effects were more prominent during memory encoding, which entailed hand motion via joystick responses. Subgroup analyses identified stronger activation of the motor cortex in JME patients with ongoing seizures compared to seizure‐free patients. Receiver‐operating characteristic curves, based on measures of motor activation, accurately discriminated both patients with JME and their siblings from healthy controls (area under the curve: 0.75 and 0.77, for JME and a combined patient‐sibling group against controls, respectively; P < .005).SignificanceMotor system hyperactivation represents a cognitive, domain‐independent endophenotype of JME. We propose measures of motor system activation as quantitative traits for future genetic imaging studies in this syndrome.

Disrupted Relationship between Hippocampal Activation and Subsequent Memory Performance in Borderline Personality Disorder

BackgroundBorderline personality disorder (BPD) is associated with subjective reports of forgetfulness and deficits on tests of memory performance. However, it is not yet known whether individuals with BPD show different patterns of activation in the hippocampus during episodic memory encoding, especially for materials that are not emotionally-valenced. MethodsParticipants with BPD (n = 20) and non-psychiatric controls (n = 21) completed a memory encoding task in which they viewed scenes without emotional content during functional magnetic resonance imaging scans. Subsequently, they completed a recognition memory test outside of the scanner and neural activation during the presentation of successfully remembered scenes was contrasted with scenes that were subsequently forgotten. ResultsControls exhibited significant left hippocampal activation during successful memory encoding, displaying greater activity during the presentation of subsequently remembered versus forgotten scenes, and the strength of this activation was related to their recognition memory performance. Although hippocampal activation was observed for the BPD group during successful memory encoding, it did not reach significance when implementing a non-parametric statistical approach. Additionally, individual hippocampal recruitment was not significantly correlated with recognition memory performance in the BPD group. The strength of this correlation, but not the overall magnitude of hippocampal activation, was significantly different between the groups. LimitationsParticipants with BPD had comorbid psychiatric diagnoses and varied treatment histories. Whether patients and controls differentially perceived emotional content in the neutral scene memoranda was not tested. ConclusionsMemory problems in BPD may be partially explained by a disrupted relationship between hippocampal activation and successful memory encoding.

In Medio Stat Virtus: intermediate levels of mind wandering improve episodic memory encoding in a virtual environment.

Episodic memory encoding is highly influenced by the availability of attentional resources. Mind wandering corresponds to a shift of attention toward task-unrelated thoughts. Few studies, however, have tested this link between memory encoding and mind wandering. The goal of the present work was to systematically investigate the influence of mind wandering during encoding on episodic memory performances in an ecological setting. Fifty-two participants were asked to navigate in a virtual urban environment. During the walk, they encountered different scenes that, unbeknownst to the participants, were target items presented in a subsequent recognition task associated with a Remember-Know-Guess paradigm. Each item triggered, after a random interval, a thought probe assessing current mind wandering. We found a significant linear positive relationship between the ratio of correctly recognized items and the overall mind wandering reported after the task. Moreover, we found a quadratic reversed U-shaped relationship between the probability of giving a 'Remember' response and both on-line and mind wandering reported a posteriori. The nearer to the medium value the level of mind wandering was, the higher was the probability to have a recollection-based recognition. Our results indicate that in a complex environment, the highest probability of actually remembering a scene would be when participants present a medium attentional level: neither distracted by inner thoughts nor too focused on the environment. This open attentional state would allow a better global processing of the environment by preventing one's attention from being captured by internal thoughts or narrowed by an over-focusing on the environment.

The association between cognitive reserve and performance-related brain activity during episodic encoding and retrieval across the adult lifespan

Remembering associations between encoded items and their contextual setting is a feature of episodic memory. Although this ability generally deteriorates with age, there is substantial variability in how older individuals perform on episodic memory tasks. A current topic of debate in the cognitive neuroscience of aging literature revolves around whether this variability may stem from genetic and/or environmental factors related to reserve, allowing some individuals to compensate for age-related decline through differential recruitment of brain regions. In this fMRI study spanning a large adult lifespan sample (N = 154), we tested whether higher cognitive reserve was associated with better task-fMRI context memory performance, and functional compensatory activity patterns in the aging brain. We used multivariate Behaviour Partial Least Squares (B-PLS) analysis to examine how age, retrieval accuracy, and a proxy measure of cognitive reserve [i.e., a composite score consisting of years of education (EDU) and crystallized IQ], impacted brain activity during the encoding and retrieval of spatial and temporal contextual details. The results indicated that age-related increases in encoding activity within anterior and lateral frontal, inferior parietal, occipito-temporal and medial temporal cortices, was correlated with better subsequent memory performance; and may be indicative of age-related functional compensation at encoding. Interestingly this compensatory pattern was not correlated with our proxy measure of cognitive reserve but was associated with total brain volume (a measure of brain reserve). However, cognitive reserve was associated with age-invariant and task-general activity in superior temporal, occipital, and left inferior frontal regions. We conclude that the relationship between cognitive reserve, brain reserve and age-related functional compensation is complex, and that EDU and IQ may not fully account for individual differences in cognitive reserve when studying well educated, healthy aging cohorts.

Neural correlates of successful emotional episodic encoding and retrieval: An SDM meta-analysis of neuroimaging studies

Episodic memory for emotional events is typically enhanced and engages additional brain mechanisms relative to episodic memory for neutral events. Many functional magnetic resonance imaging (fMRI) studies have probed the neural basis of this emotional enhancement effect on encoding processes, while relatively fewer studies have examined retrieval. Neuroimaging meta-analysis methods can summarize the brain regions associated with emotional episodic memory that are consistently activated across multiple studies. A previous ALE (Activation Likelihood Estimation) meta-analysis identified consistent activations associated with successful encoding of episodic emotional memory in the amygdala, hippocampus, and in multiple neocortical regions (Murty et al., 2010). However, since that study, meta-analysis methods have improved, and many new relevant neuroimaging studies have been published. Moreover, although qualitative reviews have summarized brain activations related to the successful retrieval of emotional episodic memory, no corresponding quantitative meta-analyses have yet been reported. Here we conducted neuroimaging meta-analyses of successful emotional memory encoding and rretrieval using Seed-based d Mapping (SDM). Relevant neuroimaging studies reporting whole-brain fMRI correlates of successful encoding and retrieval of emotional episodic memory were selected for analysis. For successful emotional memory encoding, SDM activations were found bilaterally in the medial temporal lobe (amygdala, hippocampus, entorhinal cortex, perirhinal cortex, and parahippocampal cortex), bilaterally in visual processing regions (middle temporal, gyrus, fusiform gyrus and occipital cortex) and bilaterally in the temporal pole, orbitofrontal cortex, insula, putamen, and the inferior and middle temporal gyri. In contrast to the prior meta-analysis, SDM activations were not observed in the inferior frontal gyrus or in parietal regions. For successful emotional episodic memory retrieval, SDM activations were observed in the medial temporal lobe (bilateral amygdala, left hippocampus, and left entorhinal cortex and perirhinal cortex), visual processing regions (bilateral occipital cortex and right middle temporal gyrus), prefrontal cortex (bilateral orbitofrontal cortex, bilateral inferior frontal gyrus, bilateral precentral gyrus, left middle frontal gyrus, right frontal pole) and other regions in the left hemisphere including the temporal pole, insula, putamen, angular gyrus, and parietal opercular cortex. Considerable overlap was observed between the encoding and retrieval meta-analysis maps in the medial temporal lobe (bilateral amygdala, left hippocampus, entorhinal, and perirhinal cortex), visual processing regions (bilateral occipital cortex, right middle temporal gyrus), and other regions including the left orbitofrontal cortex, left insula, left putamen, left pallidum, and left temporal pole. The current findings add to current understanding of the role of the amygdala, hippocampus, and neocortical regions in the successful encoding and retrieval of emotional episodic memory, clarify and provide an important summary of the current literature in this area, and have implications for current theories of emotional episodic memory encoding and retrieval.

Individual-specific and shared representations during episodic memory encoding and retrieval

Although human memories seem unique to each individual, they are shared to a great extent across individuals. Previous studies have examined, separately, subject-specific and cross-subject shared representations during memory encoding and retrieval, but how shared memories are formed from individually encoded representations is not clearly understood. Using a unique fMRI design involving memory encoding and retrieval, and representational similarity analysis to link representations from different individuals, brain regions, and processing stages, the current study revealed that distributed brain regions showed both subject-specific and shared neural representations during both memory encoding and retrieval. Furthermore, different brain regions showed stage-specific representational strength, with the visual cortex showing greater unique and shared representations during encoding, whereas the left angular gyrus showing greater unique and shared representations during retrieval. The neural representations during encoding were transformed during retrieval, as shown by smaller cross-subject encoding-retrieval similarity (ERS) than cross-subject similarity either during encoding or during retrieval. This cross-subject and cross-stage similarity was found both within and across regions, with strong pattern similarity between the encoded representation in VVC and the retrieved representation in the angular gyrus. Simulation analysis further suggested that these patterns could be achieved by incorporating stage-specific representational strength, and cross-region reinstatement from encoding to retrieval, but not by a common transformation from encoding to retrieval across subjects. Together, our results shed light on how memory representations are encoded and transformed to maintain individual characteristics and at the same time to create shared representations to facilitate interpersonal communication.

Longitudinal Differences in Human Hippocampal Connectivity During Episodic Memory Processing.

The question of longitudinal hippocampal functional specialization is critical to human episodic memory because an accurate understanding of this phenomenon would impact theories of mnemonic function and entail practical consequences for the clinical management of patients undergoing temporal lobe surgery. The implementation of the robotically assisted stereo electroencephalography technique for seizure mapping has provided our group with the opportunity to obtain recordings simultaneously from the anterior and posterior human hippocampus, allowing us to create an unparalleled data set of human subjects with simultaneous anterior and posterior hippocampal recordings along with several cortical regions. Using these data, we address several key questions governing functional hippocampal connectivity in human memory. First, we ask whether functional networks during episodic memory encoding and retrieval are significantly different for the anterior versus posterior hippocampus (PH). We also examine how connections differ across the 2–5 Hz versus 4–9 Hz theta frequency ranges, directly addressing the relative contribution of each of these separate bands in hippocampal–cortical interactions. While we report some overlapping connections, we observe evidence of distinct anterior versus posterior hippocampal networks during memory encoding related to frontal and parietal connectivity as well as hemispheric differences in aggregate connectivity. We frame these findings in light of the proposed AT/PM memory systems. We also observe distinct encoding versus retrieval connectivity patterns between anterior and posterior hippocampal networks, we find that overall connectivity is greater for the PH in the right hemisphere, and further that these networks significantly differ in terms of frontal and parietal connectivity. We place these findings in the context of existing theoretical treatments of human memory systems, especially the proposed AT/PM system. During memory retrieval, we observe significant differences between slow-theta (2–5 Hz) and fast-theta (4–9 Hz) connectivity between the cortex and hippocampus. Taken together, our findings describe mnemonically relevant functional connectivity differences along the longitudinal axis of the human hippocampus that will inform interpretation of models of hippocampal function that seek to integrate rodent and human data.

The Neural Mechanisms of Associative Memory Revisited: fMRI Evidence from Implicit Contingency Learning

The literature describes a basic neurofunctional antagonism between episodic memory encoding and retrieval with opposed patterns of neural activation and deactivation, particularly in posterior midline regions. This has been coined the encoding/retrieval (E/R) flip. The present fMRI study uses an innovative task paradigm to further elucidate neurofunctional relations of encoding and retrieval in associative memory. Thereby, memory encoding is implemented as implicit (non-deliberate) cognitive process, whereas the prior literature focused mainly on explicit encoding. Moreover, instead of defining brain activations related to successful (vs. unsuccessful) memory performance, the task paradigm provides proper no-memory baseline conditions. More specifically, the encoding task includes trials with non-contingent (not learnable) stimulus combinations, while the retrieval task uses trials with a simple matching exercise with no mnemonic requirements. The analyses revealed circumscribed activation in the posterior middle cingulate cortex (pMCC) together with prominent deactivation in the anterior insula cortex (aIC) as core neural substrate of implicit memory encoding. Thereby, the pMCC exhibited positive functional connectivity to the hippocampus. Memory retrieval was related to an activation pattern exactly opposed to memory encoding with deactivation in the pMCC and activation in the aIC, while the aIC additionally exhibited a negative (i.e., arguably inhibitive) functional connectivity to the pMCC. Important to note, the observed pattern of activations/de-activations in the pMCC appears to conflict with prevalent E/R flip findings. The outlined results and their (alleged) discrepancies with prior study reports are discussed primarily in the context of the default mode network’s functioning and its context-sensitive regulation. Finally, we point out the relevance of the present work for the understanding and further investigation of the neurofunctional aberrations occurring during normal and pathological aging.

Progression from Feature-Specific Brain Activity to Hippocampal Binding during Episodic Encoding.

The hallmark of episodic memory is recollecting multiple perceptual details tied to a specific spatial-temporal context. To remember an event, it is therefore necessary to integrate such details into a coherent representation during initial encoding. Here we tested how the brain encodes and binds multiple, distinct kinds of features in parallel, and how this process evolves over time during the event itself. We analyzed data from 27 human subjects (16 females, 11 males) who learned a series of objects uniquely associated with a color, a panoramic scene location, and an emotional sound while fMRI data were collected. By modeling how brain activity relates to memory for upcoming or just-viewed information, we were able to test how the neural signatures of individual features as well as the integrated event changed over the course of encoding. We observed a striking dissociation between early and late encoding processes: left inferior frontal and visuo-perceptual signals at the onset of an event tracked the amount of detail subsequently recalled and were dissociable based on distinct remembered features. In contrast, memory-related brain activity shifted to the left hippocampus toward the end of an event, which was particularly sensitive to binding item color and sound associations with spatial information. These results provide evidence of early, simultaneous feature-specific neural responses during episodic encoding that predict later remembering and suggest that the hippocampus integrates these features into a coherent experience at an event transition.SIGNIFICANCE STATEMENT Understanding and remembering complex experiences are crucial for many socio-cognitive abilities, including being able to navigate our environment, predict the future, and share experiences with others. Probing the neural mechanisms by which features become bound into meaningful episodes is a vital part of understanding how we view and reconstruct the rich detail of our environment. By testing memory for multimodal events, our findings show a functional dissociation between early encoding processes that engage lateral frontal and sensory regions to successfully encode event features, and later encoding processes that recruit hippocampus to bind these features together. These results highlight the importance of considering the temporal dynamics of encoding processes supporting multimodal event representations.

Comparison of fMRI correlates of successful episodic memory encoding in temporal lobe epilepsy patients and healthy controls

Intra-cranial electroencephalographic brain recordings (iEEG) provide a powerful tool for investigating the neural processes supporting episodic memory encoding and form the basis of experimental therapies aimed at improving memory dysfunction. However, given the invasiveness of iEEG, investigations are constrained to patients with drug-resistant epilepsy for whom such recordings are clinically indicated. Particularly in the case of temporal lobe epilepsy (TLE), neuropathology and the possibility of functional reorganization are potential constraints on the generalizability of intra-cerebral findings and pose challenges to the development of therapies for memory disorders stemming from other etiologies. Here, samples of TLE (N ​= ​16; all of whom had undergone iEEG) and age-matched healthy control (N ​= ​19) participants underwent fMRI as they studied lists of concrete nouns. fMRI BOLD responses elicited by the study words were segregated according to subsequent performance on tests of delayed free recall and recognition memory. Subsequent memory effects predictive of both successful recall and recognition memory were evident in several neural regions, most prominently in the left inferior frontal gyrus, and did not demonstrate any group differences. Behaviorally, the groups did not differ in overall recall performance or in the strength of temporal contiguity effects. However, group differences in serial position effects and false alarm rates were evident during the free recall and recognition memory tasks, respectively. Despite these behavioral differences, neuropathology associated with temporal lobe epilepsy was apparently insufficient to give rise to detectable differences in the functional neuroanatomy of episodic memory encoding relative to neurologically healthy controls. The findings provide reassurance that iEEG findings derived from experimental paradigms similar to those employed here generalize to the neurotypical population.

Meta-analytic and functional connectivity evidence from functional magnetic resonance imaging for an anterior to posterior gradient of function along the hippocampal axis.

There is considerable evidence from non-human animal studies that the anterior and posterior regions of the hippocampus have different anatomical connections and support different behavioural functions. Although there are some recent human studies using functional magnetic resonance imaging (fMRI) that have addressed this idea directly in the memory and spatial processing domains and provided support for it, there has been no broader meta-analysis of the fMRI literature to determine if there is consistent evidence for functional dissociations in anterior and posterior hippocampus across all of the different cognitive domains in which the hippocampus participates. The purpose of this review is to address this gap in our knowledge using three approaches. One approach involved PubMed searches to identify relevant fMRI papers reporting hippocampal activation during episodic encoding and retrieval, semantic retrieval, working memory, spatial navigation, simulation/scene construction, transitive inference, and social cognition tasks. The second was to use a large meta-analytic database (neurosynth) to find text terms and coactivation maps associated with the anterior and posterior hippocampal regions identified in the literature search. The third approach was to contrast the resting-state functional connectivity of the anterior and posterior hippocampal regions using a publicly available database that includes a large sample of adults. These three approaches provided converging evidence that not only are cognitive processes differently distributed along the hippocampal axis, but there also are distinct areas coactivated and functionally connected with the anterior and posterior segments. This anterior/posterior distinction involving multiple cognitive domains is consistent with the animal literature and provides strong support from fMRI for the idea of functional dissociations across the long axis of the hippocampus.

Does data cleaning improve brain state classification?

BackgroundNeuroscientists routinely seek to identify and remove noisy or artifactual observations from their data. They do so with the belief that removing such data improves power to detect relations between neural activity and behavior, which are often subtle and can be overwhelmed by noise. Whereas standard methods can exclude certain well-defined noise sources (e.g., 50/60 Hz electrical noise), in many situations there is not a clear difference between noise and signals so it is not obvious how to separate the two. Here we ask whether methods routinely used to “clean” human electrophysiological recordings lead to greater power to detect brain–behavior relations. New methodThis, to the authors’ knowledge, is the first large-scale simultaneous evaluation of multiple commonly used methods for removing noise from intracranial EEG recordings. ResultsWe find that several commonly used data cleaning methods (automated methods based on statistical signal properties and manual methods based on expert review) do not increase the power to detect univariate and multivariate electrophysiological biomarkers of successful episodic memory encoding, a well-characterized broadband pattern of neural activity observed across the brain. Comparison with existing methodsResearchers may be more likely to increase statistical power to detect physiological phenomena of interest by allocating resources away from cleaning noisy data and toward collecting more within-patient observations. ConclusionsThese findings highlight the challenge of partitioning signal and noise in the analysis of brain-behavior relations, and suggest increasing sample size and numbers of observations, rather than data cleaning, as the best approach to improving statistical power.

Sex Differences in the Neural Correlates of Spatial Context Memory Decline in Healthy Aging.

Aging is associated with episodic memory decline and alterations in memory-related brain function. However, it remains unclear if age-related memory decline is associated with similar patterns of brain aging in women and men. In the current task fMRI study, we tested the hypothesis that there are sex differences in the effect of age and memory performance on brain activity during episodic encoding and retrieval of face-location associations (spatial context memory). Forty-one women and 41 men between the ages of 21 and 76 years participated in this study. Between-group multivariate partial least squares analysis of the fMRI data was conducted to directly test for sex differences and similarities in age-related and performance-related patterns of brain activity. Our behavioral analysis indicated no significant sex differences in retrieval accuracy on the fMRI tasks. In relation to performance effects, we observed similarities and differences in how retrieval accuracy related to brain activity in women and men. Both sexes activated dorsal and lateral PFC, inferior parietal cortex, and left parahippocampal gyrus at encoding, and this supported subsequent memory performance. However, there were sex differences in retrieval activity in these same regions and in lateral occipital-temporal and ventrolateral PFC. In relation to age effects, we observed sex differences in the effect of age on memory-related activity within PFC, inferior parietal cortex, parahippocampal gyrus, and lateral occipital-temporal cortices. Overall, our findings suggest that the neural correlates of age-related spatial context memory decline differ in women compared with men.

Action boosts episodic memory encoding in humans via engagement of a noradrenergic system

We are constantly interacting with our environment whilst we encode memories. However, how actions influence memory formation remains poorly understood. Goal-directed movement engages the locus coeruleus (LC), the main source of noradrenaline in the brain. Noradrenaline is also known to enhance episodic encoding, suggesting that action could improve memory via LC engagement. Here we demonstrate, across seven experiments, that action (Go-response) enhances episodic encoding for stimuli unrelated to the action itself, compared to action inhibition (NoGo). Functional magnetic resonance imaging, and pupil diameter as a proxy measure for LC-noradrenaline transmission, indicate increased encoding-related LC activity during action. A final experiment, replicated in two independent samples, confirmed a novel prediction derived from these data that emotionally aversive stimuli, which recruit the noradrenergic system, modulate the mnemonic advantage conferred by Go-responses relative to neutral stimuli. We therefore provide converging evidence that action boosts episodic memory encoding via a noradrenergic mechanism.

Stimulation of the Posterior Cingulate Cortex Impairs Episodic Memory Encoding.

Neuroimaging experiments implicate the posterior cingulate cortex (PCC) in episodic memory processing, making it a potential target for responsive neuromodulation strategies outside of the hippocampal network. However, causal evidence for the role that PCC plays in memory encoding is lacking. In human female and male participants (N = 17) undergoing seizure mapping, we investigated functional properties of the PCC using deep brain stimulation (DBS) and stereotactic electroencephalography. We used a verbal free recall paradigm in which the PCC was stimulated during presentation of half of the study lists, whereas no stimulation was applied during presentation of the remaining lists. We investigated whether stimulation affected memory and modulated hippocampal activity. Results revealed four main findings. First, stimulation during episodic memory encoding impaired subsequent free recall, predominantly for items presented early in the study lists. Second, PCC stimulation increased hippocampal gamma-band power. Third, stimulation-induced hippocampal gamma power predicted the magnitude of memory impairment. Fourth, functional connectivity between the hippocampus and PCC predicted the strength of the stimulation effect on memory. Our findings offer causal evidence implicating the PCC in episodic memory encoding. Importantly, the results indicate that stimulation targeted outside of the temporal lobe can modulate hippocampal activity and impact behavior. Furthermore, measures of connectivity between brain regions within a functional network can be informative in predicting behavioral effects of stimulation. Our findings have significant implications for developing therapies to treat memory disorders and cognitive impairment using DBS.SIGNIFICANCE STATEMENT Cognitive impairment and memory loss are critical public health challenges. Deep brain stimulation (DBS) is a promising tool for developing strategies to ameliorate memory disorders by targeting brain regions involved in mnemonic processing. Using DBS, our study sheds light on the lesser-known role of the posterior cingulate cortex (PCC) in memory encoding. Stimulating the PCC during encoding impairs subsequent recall memory. The degree of impairment is predicted by stimulation-induced hippocampal gamma oscillations and functional connectivity between PCC and hippocampus. Our findings provide the first causal evidence implicating PCC in memory encoding and highlight the PCC as a favorable target for neuromodulation strategies using a priori connectivity measures to predict stimulation effects. This has significant implications for developing therapies for memory diseases.

Impact of adrenal hormones, reproductive aging, and major depression on memory circuitry decline in early midlife

Dehydroepiandrosterone-sulfate (DHEAS) is an adrenal androgen that is, in part, aromatized to estradiol. It continues to be produced after menopause and provides estrogenicity after depletion of ovarian hormones. Estradiol depletion contributes to memory circuitry changes over menopause, including changes in hippocampal (HIPP) and dorsolateral- and ventrolateral-prefrontal cortex (DLPFC; VLPFC) function. Further, major depressive disorder (MDD) patients have, in general, lower levels of estradiol and lower DHEAS than healthy controls, thus potentially a higher risk of adverse menopausal outcomes. We investigated whether higher DHEAS levels after menopause is associated with better memory circuitry function, especially in women with MDD. 212 adults (ages 45–55, 50% women) underwent clinical and fMRI testing. Participants performed a working memory (WM) N-back task and an episodic memory verbal encoding (VE) task during fMRI scanning. DHEAS levels were significantly associated with memory circuitry function, specifically in MDD postmenopausal women. On the WM task, lower DHEAS levels were associated with increased HIPP activity. On the VE task, lower DHEAS levels were associated with decreased activity in the HIPP and VLPFC. In contrast, there was no association between DHEAS levels and memory circuitry function in MDD pre/perimenopausal women, men, and non-MDD participants regardless of sex and reproductive status. In fact, MDD postmenopausal women with higher levels of DHEAS were similar to MDD pre/perimenopausal women and men. Thus, memory circuitry deficits associated with MDD and a lower ability of the adrenal gland to produce DHEAS after menopause may contribute to a lower ability to maintain intact memory function with age.

The Role of Hierarchical Dynamical Functions in Coding for Episodic Memory and Cognition

Behavioral research in human verbal memory function led to the initial definition of episodic memory and semantic memory. A complete model of the neural mechanisms of episodic memory must include the capacity to encode and mentally reconstruct everything that humans can recall from their experience. This article proposes new model features necessary to address the complexity of episodic memory encoding and recall in the context of broader cognition and the functional properties of neurons that could contribute to this broader scope of memory. Many episodic memory models represent individual snapshots of the world with a sequence of vectors, but a full model must represent complex functions encoding and retrieving the relations between multiple stimulus features across space and time on multiple hierarchical scales. Episodic memory involves not only the space and time of an agent experiencing events within an episode but also features shown in neurophysiological data such as coding of speed, direction, boundaries, and objects. Episodic memory includes not only a spatio-temporal trajectory of a single agent but also segments of spatio-temporal trajectories for other agents and objects encountered in the environment consistent with data on encoding the position and angle of sensory features of objects and boundaries. We will discuss potential interactions of episodic memory circuits in the hippocampus and entorhinal cortex with distributed neocortical circuits that must represent all features of human cognition.

Consumer Neuroscience and Digital/Social Media Health/Social Cause Advertisement Effectiveness.

This research investigated the use of consumer neuroscience to improve and determine the effectiveness of action/emotion-based public health and social cause (HSC) advertisements. Action-based advertisements ask individuals to ‘do something’ such as ‘act’, ‘share’, make a ‘pledge’ or complete a ‘challenge’ on behalf of a brand, such as doing ‘something good, somewhere, for someone else’. Public health messages as noncommercial advertisements attempt to positively change behavioural intent or increase awareness. Australian health expenditure was $180.7 billion AUD (Australian dollars) in 2016/17 with $17 million AUD spent on government health campaigns. However, evaluation of health advertisement effectiveness has been difficult to determine. Few studies use neuroscience techniques with traditional market research methods. A 2-part study with an exploratory design was conducted using (1) electroencephalography (EEG) using a 64 channel EEG wet cap (n = 47); and (2) a Qualtrics online psychometric survey (n = 256). Participants were asked to make a donation before and after viewing 7 HSC digital/social media advertisements and logos (6 action/emotion-based; 1 control) to measure changes in behavioural intent. Attention is considered a key factor in determining advertising effectiveness. EEG results showed theta synchronisation (increase)/alpha desynchronisation (decrease) indicating attention with episodic memory encoding. sLORETA results displayed approach responses to action/emotion-based advertisements with left prefrontal and right parietal cortex activation. EEG and survey results showed the greatest liking for the ManUp action/emotion-based advertisement which used male facial expressions of raw emotion and vulnerability. ManUp also had the highest increased amount donated after viewing. Lower theta amplitude results for the International Fund for Animal Welfare (IFAW) action/emotion-based advertisement indicated that novel (possessing distinct features) rather than attractive/conventional faces were more appealing, while the rapid presentation of faces was less effective. None of the highest peak amplitudes for each ad occurred when viewing brand logos within the advertisement. This research contributes to the academic consumer neuroscience, advertising effectiveness, and social media literature with the use of action/challenge/emotion-based marketing strategies, which remains limited, while demonstrating the value in combining EEG and neuroscientific techniques with traditional market research methods. The research provides a greater understanding of advertising effectiveness and changes in behavioural intent with managerial implications regarding the effective use of action/challenge/emotion-based HSC communications to potentially help save a life and reduce expenditure on ineffectual HSC marketing campaigns.