Asaf Gilboa

Rapid neocortical acquisition of long-term arbitrary associations independent of the hippocampus

Anterograde amnesia following hippocampal damage involves the loss of the capacity to form new declarative memories but leaves nondeclarative memory processes intact. Current theories of declarative memory suggest the existence of two complementary memory systems: a hippocampal-based system that specializes in rapid acquisition of specific events and a neocortical system that slowly learns through environmental statistical regularities and requires the initial support of the hippocampal system. Contrary to this notion, we demonstrate a neurocognitive mechanism that enables rapid acquisition of novel arbitrary associations independently of the hippocampus. This mechanism has been dubbed “fast mapping” (FM) and is believed to support the rapid acquisition of vocabulary in children as young as 16 mo of age. We used FM to teach novel word-picture associations to four profoundly amnesic patients with hippocampal system damage. Patients were able to acquire arbitrary associations through FM normally, despite profound impairment on a matched standard associative memory task. Most importantly, they retained what they learned through FM after a weeks delay, when they were around chance level on the standard task. By contrast, two patients with unilateral damage to the left polar temporal neocortex were impaired on FM, suggesting that this cortical region is critical for associative learning through FM. Left perirhinal and entorhinal cortices might also play a role in learning through FM. Contrary to current theories, these findings indicate that rapid acquisition of declarative-like (relational) memory can be accomplished independently of the hippocampus and that neocortical plasticity can be induced rapidly to support novel arbitrary associations.

Schema Representation in Patients with Ventromedial PFC Lesions

Human neuroimaging and animal studies have recently implicated the ventromedial prefrontal cortex (vmPFC) in memory schema, particularly in facilitating new encoding by existing schemas. In humans, the most conspicuous memory disorder following vmPFC damage is confabulation; strategic retrieval models suggest that aberrant schema activation or reinstatement plays a role in confabulation. This raises the possibility that beyond its role in schema-supported memory encoding, the vmPFC is also implicated in schema reinstatement itself. If that is the case, vmPFC lesions should lead to impaired schema-based operations, even on tasks that do not involve memory acquisition. To test this prediction, ten patients with vmPFC damage, four with present or prior confabulation, and a group of twelve matched healthy controls made speeded yes/no decisions as to whether words were closely related to a schema (a visit to the doctor). Ten minutes later, they repeated the task for a new schema (going to bed) with some words related to the first schema included as lures. Last, they rated the degree to which stimuli were related to the second schema. All four vmPFC patients with present or prior confabulation were impaired in rejecting lures and in classifying stimulus belongingness to the schema, even when they were not lures. Nonconfabulating patients performed comparably to healthy adults with high accuracy, comparable reaction times, and similar ratings. These results show for the first time that damage to the human vmPFC, when associated with confabulation, leads to deficient schema reinstatement, which is likely a prerequisite for schema-mediated memory integration.

Case studies continue to illuminate the cognitive neuroscience of memory

The current ubiquity of functional neuroimaging studies, and the importance they have had in elucidating brain function, obscures the fact that much of what we know about brain–behavior relationships derives largely from the study of single‐ and multiple‐patient cases. A major goal of the present review is to describe how single cases continue to uniquely and critically contribute to cognitive neuroscience theory. With several recent examples from the literature, we demonstrate that single cases can both challenge accepted dogma and generate hypotheses and theories that steer the field in new directions. We discuss recent findings from case studies that specify critical functions of the hippocampus in episodic memory and recollection, and clarify its role in nonmnemonic abilities. Although we focus on the hippocampus, we discuss other regions and the occurrence of new associative learning, as well as the involvement of the ventromedial prefrontal and parietal cortices in memory encoding and retrieval. We also describe ways of dealing with the shortcomings of case studies, and emphasize the partnership of patient and neuroimaging methods in constraining neurocognitive models of memory.

Neurobiology of Schemas and Schema-Mediated Memory

Schemas are superordinate knowledge structures that reflect abstracted commonalities across multiple experiences, exerting powerful influences over how events are perceived, interpreted, and remembered. Activated schema templates modulate early perceptual processing, as they get populated with specific informational instances (schema instantiation). Instantiated schemas, in turn, can enhance or distort mnemonic processing from the outset (at encoding), impact offline memory transformation and accelerate neocortical integration. Recent studies demonstrate distinctive neurobiological processes underlying schema-related learning. Interactions between the ventromedial prefrontal cortex (vmPFC), hippocampus, angular gyrus (AG), and unimodal associative cortices support context-relevant schema instantiation and schema mnemonic effects. The vmPFC and hippocampus may compete (as suggested by some models) or synchronize (as suggested by others) to optimize schema-related learning depending on the specific operationalization of schema memory. This highlights the need for more precise definitions of memory schemas.

Imagining Other People’s Experiences in a Person with Impaired Episodic Memory: The Role of Personal Familiarity

Difficulties remembering one’s own experiences via episodic memory may affect the ability to imagine other people’s experiences during theory of mind (ToM). Previous work shows that the same set of brain regions recruited during tests of episodic memory and future imagining are also engaged during standard laboratory tests of ToM. However, hippocampal amnesic patients who show deficits in past and future thinking, show intact performance on ToM tests, which involve unknown people or fictional characters. Here we present data from a developmental amnesic person (H.C.) and a group of demographically matched controls, who were tested on a naturalistic test of ToM that involved describing other people’s experiences in response to photos of personally familiar others (“pToM” condition) and unfamiliar others (“ToM” condition). We also included a condition that involved recollecting past experiences in response to personal photos (“EM” condition). Narratives were scored using an adapted Autobiographical Interview scoring procedure. Due to the visually rich stimuli, internal details were further classified as either descriptive (i.e., details that describe the visual content of the photo) or elaborative (i.e., details that go beyond what is visually depicted in the photo). Relative to controls, H.C. generated significantly fewer elaborative details in response to the pToM and EM photos and an equivalent number of elaborative details in response to the ToM photos. These data converge with previous neuroimaging results showing that the brain regions underlying pToM and episodic memory overlap to a greater extent than those supporting ToM. Taken together, these results suggest that detailed episodic representations supported by the hippocampus may be pivotal for imagining the experiences of personally familiar, but not unfamiliar, others.

The role of the hippocampal complex in long-term episodic memory

That the hippocampal complex plays a critical role in memory is no longer in dispute. Several essential questions remain unanswered, however, nearly 50 years after the seminal work of Scoville and Milner [1]. These include: what aspects of memory require hippocampal participation, when hippocampal participation is needed, and how various parts of the hippocampal complex are involved in these memory processes. Though there are provisional answers to each of these questions, vigorous debate continues in each case. To make matters more complicated, these questions are not independent of one another— the role played by various parts of the hippocampal complex may change over time, and with respect to the kind of memory involved. Answers to these questions force a consideration of the interactions between the hippocampal complex and the neocortex, as we will see. We begin with a brief overview of the current status of each of these debates, present some data that bear on them, and finally outline our current approach to these issues. Some definitions, however, are essential at the outset. First, what exactly is meant by the term ‘‘hippocampal complex’’? Starting from the core, the hippocampus consists of the CA fields and the dentate gyrus, the hippocampal formation incorporates the subiculum, and the hippocampal complex further includes the parahippocampal region, which incorporates the entorhinal cortex, the perirhinal cortex, and the parahippocampal gyrus. Second, what is meant by the term ‘‘memory’’? This seemingly innocent question is actually quite tangled in ways that have contributed to some of the debates in the field. The

Not all declarative memories are created equal: Fast Mapping as a direct route to cortical declarative representations.

Memory formation for newly acquired associations typically depends on hippocampal-neocortical interactions. Through the process of system-consolidation, the mnemonic binding role of the hippocampus is subsequently replaced by cortical hubs, such as the ventromedial prefrontal cortex (vmPFC) or the anterior temporal lobe (ATL). Here, using BOLD-fMRI, we compared retrieval of semantic associations acquired through Fast Mapping (FM), an incidental, exclusion-based learning procedure, to retrieval of similar associations that were intentionally acquired through Explicit Encoding (EE). Despite an identical retrieval task, the encoding histories of the retrieved semantic associations (FM vs. EE) induced distinct neural substrates and disparate related neural dynamics in time. Retrieval of associations acquired through EE engaged the expected hippocampal and vmPFC related networks. Furthermore, retrieval intentionally encoded associations gave rise to a typical overnight increase in engagement of the vmPFC and increased vmPFC-hippocampal-neocortical functional connectivity. On the other hand, retrieval of associations acquired through FM immediately engaged an ATL related network that typically supports well-established semantic knowledge, a network that did not engage the hippocampus and the vmPFC. Moreover, FM learning was associated with minimal overnight changes in the BOLD responses and in the functional connectivity. Our findings indicate that FM may induce a direct, ATL-mediated acquisition and retention of novel arbitrary associations, bypassing the initial hippocampal-cortical representation phase. A direct, ATL-mediated vocabulary acquisition through FM could support the learning and retention of new associations in young children with presumably an immature hippocampal system, and possibly even in amnesic adults with hippocampal lesions.

Hippocampal Complex Contribution to Retention and Retrieval of Recent and Remote Episodic and Semantic Memories: Evidence from Behavioral and Neuroimaging Studies of Healthy and Brain-Damaged People

For over a hundred years, it has been accepted that remote memories are less vulnerable to disruption than are recent memories. The standard consolidation model posits that the hippocampus and related structures are temporary memory structures, necessary for acquisition, retention, and retrieval of all explicit (declarative) memories until they are consolidated elsewhere in the brain. We review lesion and neuroimaging evidence showing that important distinctions exist among different types of explicit memory and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them which continue to depend on the hippocampus. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred. We conclude that the evidence favors a multiple trace theory (MTT) of memory over the traditional model, and we indicate what future work is needed to resolve disputes.

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

ABSTRACT 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. HighlightsSpatial information is a central aspect of episodic autobiographical memory.Participants often but not invariably spontaneously recall spatial information early during recall.Participants who recall spatial information early have faster reaction times.Spatial aspects of episodic autobiographical memory vary greatly across participants.Egocentric perspective during recall positively associated with precuneus volume.

Neocortical catastrophic interference in healthy and amnesic adults: A paradoxical matter of time

The human cortex can accommodate overlapping semantic information, such as synonyms, homonyms, or overlapping concepts. However, neuronal models of cortical networks predict Catastrophic Interference in conditions of overlapping information, obliterating old associations and sometimes preventing formation of new ones. It has been proposed that Catastrophic Interference in declarative memory is never observed in biological systems because of hippocampal pattern separation of competing associations. Here, we tested neocortical Catastrophic Interference during acquisition of overlapping associations through Fast Mapping; an incidental, exclusion based learning mechanism, that can support hippocampal‐independent learning. Young adults acquired picture‐label associations, either through explicit encoding or through Fast Mapping and were tested after 24 h. Overlapping/competing associations were presented either minutes (Early), or 22 h (Delayed) after learning. Catastrophic Interference was evident only following Fast Mapping, and only in the Delayed competition. In a follow‐up experiment, Medial Temporal Lobe (MTL) amnesic patients demonstrated retroactive Catastrophic Interference after the Early competition, despite normal memory for noninterfered Fast Mapping associations. Thus, following Fast Mapping, a biological system demonstrated susceptibility to Catastrophic Interference, as predicted by the neuronal‐model. Early retroactive Interference, however, can be prevented by MTL integrity.