Rhythmic Temporal Cues Coordinate Cross-frequency Phase-amplitude Coupling during Memory Encoding.

Accumulating evidence suggests that rhythmic temporal cues in the environment influence the encoding of information into long-term memory. Here, we test the hypothesis that these mnemonic effects of rhythm reflect the coupling of high-frequency (gamma) oscillations to entrained lower-frequency oscillations synchronized to the beat of the rhythm. In Study 1, we first test this hypothesis in the context of global effects of rhythm on memory, when memory is superior for visual stimuli presented in rhythmic compared with arrhythmic patterns at encoding [Jones, A., & Ward, E. V. Rhythmic temporal structure at encoding enhances recognition memory, Journal of Cognitive Neuroscience, 31, 1549-1562, 2019]. We found that rhythmic presentation of visual stimuli during encoding was associated with greater phase-amplitude coupling (PAC) between entrained low-frequency (delta) oscillations and higher-frequency (gamma) oscillations. In Study 2, we next investigated cross-frequency PAC in the context of local effects of rhythm on memory encoding, when memory is superior for visual stimuli presented in-synchrony compared with out-of-synchrony with a background auditory beat (Hickey et al., 2020). We found that the mnemonic effect of rhythm in this context was again associated with increased cross-frequency PAC between entrained low-frequency (delta) oscillations and higher-frequency (gamma) oscillations. Furthermore, the magnitude of gamma power modulations positively scaled with the subsequent memory benefit for in- versus out-of-synchrony stimuli. Together, these results suggest that the influence of rhythm on memory encoding may reflect the temporal coordination of higher-frequency gamma activity by entrained low-frequency oscillations.

Warning before misinformation exposure modulates memory encoding.

Exposure to misleading information after witnessing an event can impair future memory reports about the event. This pervasive form of memory distortion, termed the misinformation effect, can be significantly reduced if individuals are warned about the reliability of post-event information before exposure to misleading information. The present fMRI study investigated whether such prewarnings improve subsequent memory accuracy by influencing encoding-related neural activity during exposure to misinformation. We employed a repeated retrieval misinformation paradigm in which participants watched a crime video (Witnessed Event), completed an initial test of memory, listened to a post-event auditory narrative that contained consistent, neutral, and misleading details (Post-Event Information), and then completed a final test of memory. At the behavioral level, participants who were given a prewarning before the Post-Event Information were less susceptible to misinformation on the final memory test compared with participants who were not given a warning (Karanian et al., Proceedings of the National Academy of Sciences of the United States of America, 117, 22771-22779, 2020). This protection from misinformation was accompanied by greater activity in frontal regions associated with source encoding (lateral PFC) and conflict detection (ACC) during misleading trials as well as a more global reduction in activity in auditory cortex and semantic processing regions (left inferior frontal gyrus) across all trials (consistent, neutral, misleading) of the Post-Event Information narrative. Importantly, the strength of these warning-related activity modulations was associated with better protection from misinformation on the final memory test (improved memory accuracy on misleading trials). Together, these results suggest that warnings modulate encoding-related neural activity during exposure to misinformation to improve memory accuracy.

Intrinsic functional connectivity in medial temporal lobe networks is associated with susceptibility to misinformation.

Memory is notoriously fallible and susceptible to misinformation. Yet little is known about the underlying cognitive and neural mechanisms that render individuals vulnerable to this type of false memory. The current experiments take an individual differences approach to examine whether susceptibility to misinformation reflects stable underlying factors related to memory retrieval. In Study 1, we report for the first time the existence of substantial individual variability in susceptibility to misinformation in the context of repeated memory retrieval, when the misinformation effect is most pronounced. This variability was not related to an individual's tendency to adopt an episodic retrieval style during remembering (trait mnemonics). In Study 2, we next examined whether susceptibility to misinformation is related to intrinsic functional connectivity in medial temporal lobe (MTL) networks known to coordinate memory reactivation during event retrieval. Stronger resting-state functional connectivity between the MTL and cortical areas associated with visual memory reactivation (occipital cortex) was associated with better protection from misinformation. Together, these results reveal that while memory distortion is a universal property of our reconstructive memory system, susceptibility to misinformation varies at the individual level and may depend on one's ability to reactivate visual details during memory retrieval.

Leveraging Prior Knowledge to Support Short-term Memory: Exploring the Role of the Ventromedial Prefrontal Cortex.

It is well established that the ventromedial prefrontal cortex (vmPFC) plays a critical role in memory consolidation and the retrieval of remote long-term memories. Recent evidence suggests that the vmPFC also supports rapid neocortical learning and consolidation over shorter timescales, particularly when novel events align with stored knowledge. One mechanism by which the vmPFC has been proposed to support this learning is by integrating congruent information into existing neocortical knowledge during memory encoding. An important outstanding question is whether the vmPFC also plays a critical role in linking congruent information with existing knowledge before storage in long-term memory. The current study investigated this question by testing whether lesions to the vmPFC disrupt the ability to leverage stored knowledge in support of short-term memory. Specifically, we investigated the visuospatial bootstrapping effect, the phenomenon whereby immediate verbal recall of visually presented stimuli is better when stimuli appear in a familiar visuospatial array that is congruent with prior knowledge compared with an unfamiliar visuospatial array. We found that the overall magnitude of the bootstrapping effect did not differ between patients with vmPFC lesions and controls. However, a reliable bootstrapping effect was not present in the patient group alone. Post hoc analysis of individual patient performance revealed that the bootstrapping effect did not differ from controls in nine patients but was reduced in two patients. Although mixed, these results suggest that vmPFC lesions do not uniformly disrupt the ability to leverage stored knowledge in support of short-term memory.

Protecting memory from misinformation: Warnings modulate cortical reinstatement during memory retrieval.

Exposure to even subtle forms of misleading information can significantly alter memory for past events. Memory distortion due to misinformation has been linked to faulty reconstructive processes during memory retrieval and the reactivation of brain regions involved in the initial encoding of misleading details (cortical reinstatement). The current study investigated whether warning participants about the threat of misinformation can modulate cortical reinstatement during memory retrieval and reduce misinformation errors. Participants watched a silent video depicting a crime (original event) and were given an initial test of memory for the crime details. Then, participants listened to an auditory narrative describing the crime in which some original details were altered (misinformation). Importantly, participants who received a warning about the reliability of the auditory narrative either before or after exposure to misinformation demonstrated less susceptibility to misinformation on a final test of memory compared to unwarned participants. Warned and unwarned participants also demonstrated striking differences in neural activity during the final memory test. Compared to participants who did not receive a warning, participants who received a warning (regardless of its timing) demonstrated increased activity in visual regions associated with the original source of information as well as decreased activity in auditory regions associated with the misleading source of information. Stronger visual reactivation was associated with reduced susceptibility to misinformation, whereas stronger auditory reactivation was associated with increased susceptibility to misinformation. Together, these results suggest that a simple warning can modulate reconstructive processes during memory retrieval and reduce memory errors due to misinformation.

Memory in time: Neural tracking of low-frequency rhythm dynamically modulates memory formation.

Time is a critical component of episodic memory. Yet it is currently unclear how different types of temporal signals are represented in the brain and how these temporal signals support episodic memory. The current study investigated whether temporal cues provided by low-frequency environmental rhythms influence memory formation. Specifically, we tested the hypothesis that neural tracking of low-frequency rhythm serves as a mechanism of selective attention that dynamically biases the encoding of visual information at specific moments in time. Participants incidentally encoded a series of visual objects while passively listening to background, instrumental music with a steady beat. Objects either appeared in-synchrony or out-of-synchrony with the background beat. Participants were then given a surprise subsequent memory test (in silence). Results revealed significant neural tracking of the musical beat at encoding, evident in increased electrophysiological power and inter-trial phase coherence at the perceived beat frequency (1.25 â€‹Hz). Importantly, enhanced neural tracking of the background rhythm at encoding was associated with superior subsequent memory for in-synchrony compared to out-of-synchrony objects at test. Together, these results provide novel evidence that the brain spontaneously tracks low-frequency musical rhythm during naturalistic listening situations, and that the strength of this neural tracking is associated with the effects of rhythm on higher-order cognitive processes such as episodic memory.

Retrieval practice improves item memory but not source memory in the context of stress.

Smith, Floerke, and Thomas (2016) demonstrated that learning by repeated testing, or retrieval practice, reduced stress-related memory impairment when compared to learning by repeatedly studying material. In the present experiment, we tested whether, relative to study practice, retrieval practice would improve post-stress memory by increasing access to both item and source information. Participants learned two wordlists, which were temporally segregated to facilitate distinction between the two lists. Participants returned one week later for stress induction and two memory tests. Each test featured a recognition test that was given to assess item memory accessibility, and a list-discrimination task that was given to assess source memory. Relative to study practice, successful retrieval practice during learning reduced false alarms but did not improve source memory on the post-stress test. Results are discussed as they relate to current theories surrounding stress effects and retrieval practice effects.

A role for the medial temporal lobe in feedback-driven learning: evidence from amnesia.

The ability to learn from feedback is a key component of adaptive behavior. This type of learning is traditionally thought to depend on neural substrates in the striatum and not on the medial temporal lobe (MTL). Here we show that in humans the MTL becomes necessary for feedback-based learning when feedback is delayed. Specifically, amnesic patients with MTL damage were impaired at probabilistic learning of cue-outcome associations when response-contingent feedback was delayed by a few seconds, but not when feedback was immediate. By contrast, patients with striatal dysfunction due to Parkinson's disease demonstrated the opposite pattern: impaired learning when trial-by-trial feedback was immediate but not when feedback was delayed, indicating that the striatum is necessary for learning only when feedback is immediate. Together, these results reveal that multiple complementary learning processes support what appears to be identical behavior in healthy individuals and point to an important role for the MTL in feedback-driven learning.

Losing sight of the future: Impaired semantic prospection following medial temporal lobe lesions.

The ability to imagine the future (prospection) relies on many of the same brain regions that support memory for the past. To date, scientific research has primarily focused on the neural substrates of episodic forms of prospection (mental simulation of spatiotemporally specific future events); however, little is known about the neural substrates of semantic prospection (mental simulation of future nonpersonal facts). Of particular interest is the role of the medial temporal lobes (MTLs), and specifically the hippocampus. Although the hippocampus has been proposed to play a key role in episodic prospection, recent evidence suggests that it may not play a similar role in semantic prospection. To examine this possibility, amnesic patients with MTL lesions were asked to imagine future issues occurring in the public domain. The results showed that patients could list general semantic facts about the future, but when probed to elaborate, patients produced impoverished descriptions that lacked semantic detail. This impairment occurred despite intact performance on standard neuropsychological tests of semantic processing and did not simply reflect deficits in narrative construction. The performance of a patient with damage limited to the hippocampus was similar to that of the remaining patients with MTL lesions and amnesic patients' impaired elaboration of the semantic future correlated with their impaired elaboration of the semantic past. Together, these results provide novel evidence from MTL amnesia that memory and prospection are linked in the semantic domain and reveal that the MTLs play a critical role in the construction of detailed, multi-element semantic simulations.

Medial temporal lobe damage causes deficits in episodic memory and episodic future thinking not attributable to deficits in narrative construction.

The medial temporal lobe (MTL) makes critical contributions to episodic memory, but its contributions to episodic future thinking remain a matter of debate. By one view, imagining future events relies on MTL mechanisms that also support memory for past events. Alternatively, it has recently been suggested that future thinking is independent of MTL-mediated processes and can be supported by regions outside the MTL. The current study investigated the nature and necessity of MTL involvement in imagining the future and tested the novel hypothesis that the MTL contributes to future thinking by supporting online binding processes related to narrative construction. Human amnesic patients with well characterized MTL damage and healthy controls constructed narratives about (1) future events, (2) past events, and (3) visually presented pictures. While all three tasks place similar demands on narrative construction, only the past and future conditions require memory/future thinking to mentally generate relevant narrative information. Patients produced impoverished descriptions of both past and future events but were unimpaired at producing detailed picture narratives. In addition, future-thinking performance positively correlated with episodic memory performance but did not correlate with picture narrative performance. Finally, future-thinking impairments were present when MTL lesions were restricted to the hippocampus and did not depend on the presence of neural damage outside the MTL. These results indicate that the ability to generate and maintain a detailed narrative is preserved in amnesia and suggest that a common MTL mechanism supports both episodic memory and episodic future thinking.

Remote memory function and dysfunction in Korsakoff's syndrome.

Korsakoff's syndrome (KS) is a pervasive disorder of memory characterized by both anterograde and retrograde amnesia. Although retrograde memory impairment in KS has been less frequently studied, the status of remote memory in KS has been tested across a number of different tasks that measure knowledge of public information (e.g., famous faces/news events), general semantic information (e.g., vocabulary words), personal semantic information (e.g., facts about oneself), and autobiographical events (e.g., events from one's personal past). In each of these domains, Korsakoff patients demonstrate remote memory impairments that can extend back many years or decades. In addition, a majority of studies report that the extensive remote memory impairment in KS is temporally graded, with relative preservation of memories from childhood and early adulthood. The current paper reviews published experimental studies of remote memory in KS, with particular attention paid to (a) the selectivity of the deficit with respect to the age of the memory and (b) the relationship of memory impairment to underlying neuropathology. We discuss the significance of the reported pattern and extent of remote memory impairment with respect to theories about the nature of the underlying cognitive deficits in KS.

MEDIAL TEMPORAL LOBE CONTRIBUTIONS TO FUTURE THINKING: EVIDENCE FROM NEUROIMAGING AND AMNESIA.

Following early amnesic case reports, there is now considerable evidence suggesting a link between remembering the past and envisioning the future. This link is evident in the overlap in neural substrates as well as cognitive processes involved in both kinds of tasks. While constructing a future narrative requires multiple processes, neuroimaging and lesion data converge on a critical role for the medial temporal lobes (MTL) in retrieving and recombining details from memory in the service of novel simulations. Deficient detail retrieval and recombination may lead to impairments not only in episodic, but also in semantic prospection. MTL contributions to scene construction and mental time travel may further compound impairments in amnesia on tasks that pose additional demands on these processes, but are unlikely to form the core deficit underlying amnesics' cross-domain future thinking impairment. Future studies exploring the role of episodic memory in other forms of self-projection or future-oriented behaviour may elucidate further the adaptive role of memory.

Multiple forms of learning yield temporally distinct electrophysiological repetition effects.

Prior experience with a stimulus leads to multiple forms of learning that facilitate subsequent behavior (repetition priming) and neural processing (repetition suppression). Learning can occur at the level of stimulus-specific features (stimulus learning), associations between stimuli and selected decisions (stimulus-decision learning), and associations between stimuli and selected responses (stimulus-response learning). Although recent functional magnetic resonance imaging results suggest that these distinct forms of learning are associated with repetition suppression (neural priming) in dissociable regions of frontal and temporal cortex, a critical question is how these different forms of learning influence cortical response dynamics. Here, electroencephalography (EEG) measured the temporal structure of neural responses when participants classified novel and repeated stimuli, using a design that isolated the effects of distinct levels of learning. Event-related potential and spectral EEG analyses revealed electrophysiological effects due to stimulus, stimulus-decision, and stimulus-response learning, demonstrating experience-dependent cortical modulation at multiple levels of representation. Stimulus-level learning modulated cortical dynamics earlier in the temporal-processing stream relative to stimulus-decision and stimulus-response learning. These findings indicate that repeated stimulus processing, including the mapping of stimuli to decisions and actions, is influenced by stimulus-level and associative learning mechanisms that yield multiple forms of experience-dependent cortical plasticity.

Riding the slow wave: Exploring the role of entrained low-frequency oscillations in memory formation.

Neural oscillations are proposed to support a variety of behaviors, including long-term memory, yet their functional significance remains an active area of research. Here, we explore a potential functional role of low-frequency cortical oscillations in episodic memory formation. Recent theories suggest that low-frequency oscillations orchestrate rhythmic attentional sampling of the environment by dynamically modulating neural excitability across time. When these oscillations entrain to low-frequency rhythms present in the environment, such as speech or music, the brain can build temporal predictions about the onset of relevant events so that these events can be more efficiently processed. Building upon this literature, we propose that entrained low-frequency oscillations may similarly influence the temporal dynamics of episodic memory by rhythmically modulating encoding across time (mnemonic sampling). Central to this proposal is the phenomenon of cross-frequency phase-amplitude coupling, whereby the amplitudes of faster (higher frequency) rhythms, such as gamma oscillations, couple to the phase of slower (lower-frequency) rhythms entrained to environmental stimuli. By imposing temporal structure on higher-frequency oscillatory activity previously linked to memory formation, entrained low-frequency oscillations could dynamically orchestrate memory formation and optimize encoding at specific moments in time. We discuss prior experimental and theoretical work relevant to this proposal.

The language of mental images: Characterizing hippocampal contributions to imageable word use during event construction.

Accumulating evidence suggests that the hippocampus plays a critical role in the creative and flexible use of language at the sentence or discourse level. Yet it is currently unclear whether the hippocampus also supports language use at the level of single words. A recent study by Hilverman et al. (2017) found that amnesic patients with hippocampal damage use less imageable words when describing autobiographical episodes compared to healthy controls, but this deficit was attributed to patients' deficits in episodic memory rather than impairments in linguistic functions of the hippocampus per se. Yet, in addition to affecting word use by way of its role in memory, the hippocampus could also impact language use more directly. The current study aimed to test this hypothesis by investigating the status of imageable word use in amnesia during two different types of language production tasks. In Experiment 1, participants constructed narratives about events depicted in visually presented pictures (picture narratives). In Experiment 2, participants constructed verbal narratives about remembered events from the past or simulated events in the future (past/future narratives). Across all types of narratives, patients produced words that were rated as having similar levels of imageability compared to controls. Importantly, this was the case both in patients' picture narratives, which did not require generating details from episodic memory and were matched to those of controls with respect to narrative content, and in patients' narratives about past/future events, which required generating details from memory and which were reduced in narrative content compared to those of controls. These results distinguish between the quantity and quality of individual linguistic details produced in amnesia during narrative construction, and suggest that the use of imageable linguistic representations does not depend on intact episodic memory and can be supported by regions outside the hippocampus.

Environmental rhythms orchestrate neural activity at multiple stages of processing during memory encoding: Evidence from event-related potentials.

Accumulating evidence suggests that rhythmic temporal structures in the environment influence memory formation. For example, stimuli that appear in synchrony with the beat of background, environmental rhythms are better remembered than stimuli that appear out-of-synchrony with the beat. This rhythmic modulation of memory has been linked to entrained neural oscillations which are proposed to act as a mechanism of selective attention that prioritize processing of events that coincide with the beat. However, it is currently unclear whether rhythm influences memory formation by influencing early (sensory) or late (post-perceptual) processing of stimuli. The current study used stimulus-locked event-related potentials (ERPs) to investigate the locus of stimulus processing at which rhythm temporal cues operate in the service of memory formation. Participants viewed a series of visual objects that either appeared in-synchrony or out-of-synchrony with the beat of background music and made a semantic classification (living/non-living) for each object. Participants' memory for the objects was then tested (in silence). The timing of stimulus presentation during encoding (in-synchrony or out-of-synchrony with the background beat) influenced later ERPs associated with post-perceptual selection and orienting attention in time rather than earlier ERPs associated with sensory processing. The magnitude of post-perceptual ERPs also differed according to whether or not participants demonstrated a mnemonic benefit for in-synchrony compared to out-of-synchrony stimuli, and was related to the magnitude of the rhythmic modulation of memory performance across participants. These results support two prominent theories in the field, the Dynamic Attending Theory and the Oscillation Selection Hypothesis, which propose that neural responses to rhythm act as a core mechanism of selective attention that optimize processing at specific moments in time. Furthermore, they reveal that in addition to acting as a mechanism of early attentional selection, rhythm influences later, post-perceptual cognitive processes as events are transformed into memory.

Repetition priming in amnesia: Distinguishing associative learning at different levels of abstraction.

Learned associations between stimuli and responses make important contributions to priming. The current study aimed to determine whether medial temporal lobe (MTL) binding mechanisms mediate this learning. Prior studies implicating the MTL in stimulus-response (S-R) learning have not isolated associative learning at the response level from associative learning at other levels of representation (e.g., task sets or decisions). The current study investigated whether the MTL is specifically involved in associative learning at the response level by testing a group of amnesic patients with MTL damage on a priming paradigm that isolates associative learning at the response level. Patients demonstrated intact priming when associative learning was isolated to the stimulus-response level. In contrast, their priming was reduced when associations between stimuli and more abstract representations (e.g., stimulus-task or stimulus-decision associations) could contribute to performance. These results provide novel neuropsychological evidence that S-R contributions to priming can be supported by regions outside the MTL, and suggest that the MTL may play a critical role in linking stimuli to more abstract tasks or decisions during priming.

Temporal predictions provided by musical rhythm influence visual memory encoding.

Selective attention plays a key role in determining what aspects of our environment are encoded into long-term memory. Auditory rhythms with a regular beat provide temporal expectations that entrain attention and facilitate perception of visual stimuli aligned with the beat. The current study investigated whether entrainment to background auditory rhythms also facilitates higher-level cognitive functions such as episodic memory. In a series of experiments, we manipulated temporal attention through the use of rhythmic, instrumental music. In Experiment 1A and 1B, we found that background musical rhythm influenced the encoding of visual targets into memory, evident in enhanced subsequent memory for targets that appeared in-synchrony compared to out-of-synchrony with the background beat. Response times at encoding did not differ for in-synchrony compared to out-of-synchrony stimuli, suggesting that the rhythmic modulation of memory does not simply reflect rhythmic effects on perception and action. Experiment 2 investigated whether rhythmic effects on response times emerge when task procedures more closely match prior studies that have demonstrated significant auditory entrainment effects. Responses were faster for in-synchrony compared to out-of-synchrony stimuli when participants performed a more perceptually-oriented task that did not contain intervening recognition memory tests, suggesting that rhythmic effects on perception and action depend on the nature of the task demands. Together, these results support the hypothesis that rhythmic temporal regularities provided by background music can entrain attention and influence the encoding of visual stimuli into memory.

Self-related processing and future thinking: Distinct contributions of ventromedial prefrontal cortex and the medial temporal lobes.

Episodic future thinking depends on a core network of regions that involves, in addition to the medial temporal lobes (MTL), the ventromedial prefrontal cortex (vmPFC). Neuroimaging studies suggest that vmPFC is particularly involved when future thinking requires consideration of self-relevant information, but lesion evidence for a special role of vmPFC in constructing self-relevant scenarios is limited. To clarify the involvement of vmPFC in future thinking, eight patients with vmPFC lesions were asked to imagine future events pertaining to the self or to another person, and their performance was contrasted with that of eight patients with MTL lesions. Patients with vmPFC lesions were no more detailed in their description of future events pertaining to the self than of events pertaining to another person. In contrast, like controls, patients with MTL lesions showed a self-benefit, despite impoverished performance overall. These findings accord with evidence from neuroimaging studies and elucidate the distinct contributions of vmPFC and MTL to future thinking.

Using Practice Testing, Public Speaking, and Source Monitoring to Examine the Influences of Learning Strategies and Stress on Episodic Memory.

Prior research demonstrated that learning information via retrieval practice, which entails studying and taking practice tests, resulted in less memory impairment under stress than learning information via repeated studying. The present experiment combined three experimental procedures to further examine the memory mechanisms underlying the efficacy of retrieval practice in the context of stress. A list-discrimination task was implemented, in which participants learned two distinct wordlists. This was combined with a retrieval-practice manipulation, as half of the participants engaged in practice testing and half engaged in conventional studying during learning. A week later, participants underwent stress induction, using the Trier Social Stress Test. Before and after stress induction, participants completed tests of item and source memory (i.e., list discrimination). The combination of these three procedures yielded informative results: retrieval practice, in the context of stress, improved item memory but not source memory relative to conventional studying. Limitations and future directions for the use of this methodology are discussed.