Neural similarity between overlapping events at learning differentially affects reinstatement across the cortex.

Episodic memory often involves high overlap between the actors, locations, and objects of everyday events. Under some circumstances, it may be beneficial to distinguish, or differentiate, neural representations of similar events to avoid interference at recall. Alternatively, forming overlapping representations of similar events, or integration, may aid recall by linking shared information between memories. It is currently unclear how the brain supports these seemingly conflicting functions of differentiation and integration. We used multivoxel pattern similarity analysis (MVPA) of fMRI data and neural-network analysis of visual similarity to examine how highly overlapping naturalistic events are encoded in patterns of cortical activity, and how the degree of differentiation versus integration at encoding affects later retrieval. Participants performed an episodic memory task in which they learned and recalled naturalistic video stimuli with high feature overlap. Visually similar videos were encoded in overlapping patterns of neural activity in temporal, parietal, and occipital regions, suggesting integration. We further found that encoding processes differentially predicted later reinstatement across the cortex. In visual processing regions in occipital cortex, greater differentiation at encoding predicted later reinstatement. Higher-level sensory processing regions in temporal and parietal lobes showed the opposite pattern, whereby highly integrated stimuli showed greater reinstatement. Moreover, integration in high-level sensory processing regions during encoding predicted greater accuracy and vividness at recall. These findings provide novel evidence that encoding-related differentiation and integration processes across the cortex have divergent effects on later recall of highly similar naturalistic events.

Sensitivity of amplitude and phase based MEG measures of interhemispheric connectivity during unilateral finger movements.

Interactions between different brain regions can be revealed by dependencies between their neuronal oscillations. We examined the sensitivity of different oscillatory connectivity measures in revealing interhemispheric interactions between primary motor cortices (M1s) during unilateral finger movements. Based on frequency, amplitude, and phase of the oscillations, a number of metrics have been developed to measure connectivity between brain regions, and each metric has its own strengths, weaknesses, and pitfalls. Taking advantage of the well-known movement-related modulations of oscillatory amplitude in M1s, this study compared and contrasted a number of leading connectivity metrics during distinct phases of oscillatory power changes. Between M1s during unilateral movements, we found that phase-based metrics were effective at revealing connectivity during the beta (15-35 Hz) rebound period linked to movement termination, but not during the early period of beta desynchronization occurring during the movement itself. Amplitude correlation metrics revealed robust connectivity during both periods. Techniques for estimating the direction of connectivity had limited success. Granger Causality was not well suited to studying these connections because it was strongly confounded by differences in signal-to-noise ratio linked to modulation of beta amplitude occurring during the task. Phase slope index was suggestive but not conclusive of a unidirectional influence between motor cortices during the beta rebound. Our findings suggest that a combination of amplitude and phase-based metrics is likely required to fully characterize connectivity during task protocols that involve modulation of oscillatory power, and that amplitude-based metrics appear to be more sensitive despite the lack of directional information.

Precuneus stimulation alters the neural dynamics of autobiographical memory retrieval.

Autobiographical memory (AM) unfolds over time, but little is known about the dynamics of its retrieval. Space-based models of memory implicate the hippocampus, retrosplenial cortex, and precuneus in early memory computations. Here we used transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) to investigate the causal role of the precuneus in the dynamics of AM retrieval. During early memory search and construction, precuneus stimulation compared to vertex stimulation led to delayed evoked neural activity within 1000 â€‹ms after cue presentation. During later memory elaboration, stimulation led to decreased sustained positivity. We further identified a parietal late positive component during memory elaboration, the amplitude of which was associated with spatial perspective during recollection. This association was disrupted following precuneus stimulation, suggesting that this region plays an important role in the neural representation of spatial perspective during AM. These findings demonstrate a causal role for the precuneus in early AM retrieval, during memory search before a specific memory is accessed, and in spatial context reinstatement during the initial stages of memory elaboration and re-experiencing. By utilizing the high temporal resolution of MEG and the causality of TMS, this study helps clarify the neural correlates of early naturalistic memory retrieval.

Memory, Decision-Making, and the Ventromedial Prefrontal Cortex (vmPFC): The Roles of Subcallosal and Posterior Orbitofrontal Cortices in Monitoring and Control Processes.

The ventromedial prefrontal cortex (vmPFC) prominently and separately features in neurobiological models of decision-making (e.g., value-encoding) and of memory (e.g., automatic veracity-monitoring). Recent decision-making models propose value judgments that inherently comprise of second-order confidence estimates. These demonstrate quadratic relationships with first-order judgments and are automatically encoded in vmPFC activity. Memory studies use Quantity-Accuracy Profiles to capture similar first-order and second-order meta-mnemonic processes, suggesting convergence across domains. Patients with PFC damage answered general knowledge questionnaires under 2 conditions. During forced report, they chose an answer and rated the probability of it being correct (first-order "monitoring"). During free report, they could choose to volunteer or withhold their previous answers (second-order "control") to maximize performance. We found quadratic relationships between first-order and second-order meta-mnemonic processes; voxel-based lesion-symptom mapping demonstrated that vmPFC damage diminished that relationship. Furthermore, damage to subcallosal vmPFC was specifically associated with impaired monitoring and additional damage to posterior orbitofrontal cortex led to deficient control. In decision-making, these regions typically support valuation and choice, respectively. Persistent spontaneous confabulation (false memory production) confirmed the clinical relevance of these dissociations. Compared with patients with no confabulation history, patients who currently confabulate were impaired on both monitoring and control, whereas former confabulators demonstrated impaired monitoring but intact control.

Enhanced reinstatement of naturalistic event memories due to hippocampal-network-targeted stimulation.

Episodic memory involves the reinstatement of distributed patterns of brain activity present when events were initially experienced. The hippocampus is thought to coordinate reinstatement via its interactions with a network of brain regions, but this hypothesis has not been causally tested in humans. The current study directly tested the involvement of the hippocampal network in reinstatement using network-targeted noninvasive stimulation. We measured reinstatement of multi-voxel patterns of functional magnetic resonance imaging (fMRI) activity during encoding and retrieval of naturalistic video clips depicting everyday activities. Reinstatement of video-specific activity patterns was robust in posterior parietal and occipital areas previously implicated in event reinstatement. Theta-burst stimulation targeting the hippocampal network increased video-specific reinstatement of fMRI activity patterns in occipital cortex and improved memory accuracy relative to stimulation of a control out-of-network location. Furthermore, stimulation targeting the hippocampal network influenced the trial-by-trial relationship between hippocampal activity during encoding and later reinstatement in occipital cortex. These findings implicate the hippocampal network in the reinstatement of spatially distributed patterns of event-specific activity and identify a role for the hippocampus in encoding complex naturalistic events that later undergo cortical reinstatement.

Testing network properties of episodic memory using non-invasive brain stimulation.

Episodic memory depends on the hippocampus and its coordination with a distributed network of interconnected brain areas. Recent findings indicate that the function of this network can be altered using network-targeted transcranial magnetic stimulation (TMS). These stimulation experiments have identified increases in episodic memory and the network-wide coordination it requires. Network-target stimulation differs from the dominant framework for TMS experiments, in which stimulation has been considered as a focal virtual lesion. We offer a conceptual framework for important distinctions between network-wide and focal effects of stimulation on episodic memory and discuss factors that may influence the quality and quantity of stimulation effects. Findings from these experiments indicate that many properties of episodic memory can be effectively studied at the network level via noninvasive stimulation.

A causal role for the precuneus in network-wide theta and gamma oscillatory activity during complex memory retrieval.

Complex memory of personal events is thought to depend on coordinated reinstatement of cortical representations by the medial temporal lobes (MTL). MTL-cortical theta and gamma coupling is believed to mediate such coordination, but which cortical structures are critical for retrieval and how they influence oscillatory coupling is unclear. We used magnetoencephalography (MEG) combined with continuous theta burst stimulation (cTBS) to (i) clarify the roles of theta and gamma oscillations in network-wide communication during naturalistic memory retrieval, and (ii) understand the causal relationship between cortical network nodes and oscillatory communication. Retrieval was associated with MTL-posterior neocortical theta phase coupling and theta-gamma phase-amplitude coupling relative to a rest period. Precuneus cTBS altered MTL-neocortical communication by modulating theta and gamma oscillatory coupling. These findings provide a mechanistic account for MTL-cortical communication and demonstrate that the precuneus is a critical cortical node of oscillatory activity, coordinating cross-regional interactions that drive remembering.

Rapid Cortical Plasticity Supports Long-Term Memory Formation.

The standard systems consolidation account posits that recently formed memories are initially dependent on the hippocampus and only gradually become instantiated in neocortical networks over a period of weeks to years. However, recent animal and human research has identified rapid formation of cortical engrams at the time of learning that can support hippocampal-independent memories within hours or days. Conditions that promote rapid cortical learning include relatedness to prior knowledge, activation of knowledge in the service of action selection or active discovery, and repeated retrieval. Here, we propose that cortical hubs can support rapid learning through synchronous activation of sensorimotor representational cortices. Candidate neurobiological mechanisms include unmasking of latent synaptic connections and rapid synaptic remodeling driven by disinhibitory processes.

The precuneus and hippocampus contribute to individual differences in the unfolding of spatial representations during episodic autobiographical memory.

Spatial information is a central aspect of episodic autobiographical memory (EAM). Space-based theories of memory, including cognitive map and scene construction models, posit that spatial reinstatement is a required process during early event recall. Spatial information can be represented from both allocentric (third-person) and egocentric (first-person) perspectives during EAM, with egocentric perspectives being important for mental imagery and supported by the precuneus. Individuals differ in their tendency to rely on allocentric or egocentric information, and in general, the subjective experience of remembering in EAM differs greatly across individuals. Here we examined individual differences in spatial aspects of EAM, how such differences influence the vividness and temporal order of recollection, and their anatomical correlates. We cued healthy young participants (n =63) with personally familiar locations and non-locations. We examined how cue type affects (i) retrieval dynamics and (ii) phenomenological aspects of remembering, and related behavioural performance to regional brain volumes (n =42). Participants tended to spontaneously recall spatial information early during recollection, even in the absence of spatial cues, and individuals with a stronger tendency to recall space first also displayed faster reaction times. Across participants, place-cued memories were re-experienced more vividly and were richer in detail than those cued by objects, but not more than those cued by familiar persons. Volumetric differences were associated with behavioural performance such that egocentric remembering was positively associated with precuneus volume. Hippocampal CA2/CA3 volumes were associated with the tendency to recall place-cued memories less effortfully. Consistent with scene construction theories, this study suggests that spatial information is reinstated early and contributes to the efficiency and phenomenology of EAM. However, early recall of spatial information is not universal and other routes to recall exist, challenging some aspects of these models. Variability among participants highlights the importance of an individual differences approach to studying EAM.

A boost of confidence: The role of the ventromedial prefrontal cortex in memory, decision-making, and schemas.

The ventromedial prefrontal cortex (vmPFC) has been implicated in a wide array of functions across multiple domains. In this review, we focus on the vmPFC's involvement in mediating strategic aspects of memory retrieval, memory-related schema functions, and decision-making. We suggest that vmPFC generates a confidence signal that informs decisions and memory-guided behaviour. Confidence is central to these seemingly diverse functions: (1) Strategic retrieval: lesions to the vmPFC impair an early, automatic, and intuitive monitoring process ("feeling of rightness"; FOR) often associated with confabulation (spontaneous reporting of erroneous memories). Critically, confabulators typically demonstrate high levels of confidence in their false memories, suggesting that faulty monitoring following vmPFC damage may lead to indiscriminate confidence signals. (2) Memory schemas: the vmPFC is critically involved in instantiating and maintaining contextually relevant schemas, broadly defined as higher level knowledge structures that encapsulate lower level representational elements. The correspondence between memory retrieval cues and these activated schemas leads to FOR monitoring. Stronger, more elaborate schemas produce stronger FOR and influence confidence in the veracity of memory candidates. (3) Finally, we review evidence on the vmPFC's role in decision-making, extending this role to decision-making during memory retrieval. During non-mnemonic and mnemonic decision-making the vmPFC automatically encodes confidence. Confidence signal in the vmPFC is revealed as a non-linear relationship between a first-order monitoring assessment and second-order action or choice. Attempting to integrate the multiple functions of the vmPFC, we propose a posterior-anterior organizational principle for this region. More posterior vmPFC regions are involved in earlier, automatic, subjective, and contextually sensitive functions, while more anterior regions are involved in controlled actions based on these earlier functions. Confidence signals reflect the non-linear relationship between first-order, posterior-mediated and second-order, anterior-mediated processes and are represented along the entire axis.