The hippocampus and inferential reasoning: building memories to navigate future decisions

Abstract

A critical aspect of inferential reasoning is the ability to form relationships between items or events that were not experienced together. This review considers different perspectives on the role of the hippocampus in successful inferential reasoning during both memory encoding and retrieval. Intuitively, inference can be thought of as a logical process by which elements of individual existing memories are retrieved and recombined to answer novel questions. Such flexible retrieval is sub-served by the hippocampus and is thought to require specialized hippocampal encoding mechanisms that discretely code events such that event elements are individually accessible from memory. In addition to retrieval-based inference, recent research has also focused on hippocampal processes that support the combination of information acquired across multiple experiences during encoding. This mechanism suggests that by recalling past events during new experiences, connections can be created between newly formed and existing memories. Such hippocampally mediated memory integration would thus underlie the formation of networks of related memories that extend beyond direct experience to anticipate future judgments about the relationships between items and events. We also discuss integrative encoding in the context of emerging evidence linking the hippocampus to the formation of schemas as well as prospective theories of hippocampal function that suggest memories are actively constructed to anticipate future decisions and actions.

Keywords: encoding; flexibility; hippocampus; inference; integration; memory; retrieval.

Figures

Figure 1

Inference tasks. (A) Transitive inference task with six elements. A set of overlapping training pairs forms an ordered hierarchy of relationships. Participants learn each individual training pair via feedback-based learning (e.g., A > B) and are then tested on novel inference and novel non-inference judgments. Items in inferential probe trials may be separated by one element in the hierarchy (e.g., B ? D, indicated as 1°) or two elements (e.g., B ? E, indicated as 2°). Novel non-inferential probes test knowledge of the relationship between the end items of the hierarchy (A ? F). (B) Acquired equivalence task. In stage one of training, participants are trained via feedback to associate two faces (F1 and F2) with a particular scene (S1). In stage two, participants learn to select a second scene (S2) when cued with one of the faces (F1). Inference is then measured as the proportion of trials on which participants choose S2 when cued with F2. The schematic depicts trained stimulus–response relationships (solid black arrows) and inferential relationships (dashed black arrows). (C) Associative inference task. Participants learn an overlapping set of associations (here, face–house associations), in which two stimuli (a man and a woman) are associated with a common third item (a house). Novel inference trials evaluate knowledge for the indirect relationship between items (who lives together in the same house).

Figure 2

Lesion and neuropsychological studies assessing the critical role of hippocampus in inference.(A) Associative inference task. Left panel: mean number of errors to criterion on training of two sets of overlapping associations (e.g., AB, BC). Right panel: Inference performance as measured by a preference index for indirectly related item (e.g., selecting C when cued with A). White bars denote sham operated control rats; blue bars denote hippocampally lesioned rats. Hippocampally lesioned rats learn individual relationships between item pairs at a rate similar to control rats, but fail on the inference test. Adapted by permission from Bunsey and Eichenbaum (1996), copyright 1996 Macmillan Publishers Ltd. (B) Transitive inference task. Rats with lesions disconnecting the hippocampus from its subcortical (fornix, dark blue bars) or cortical (entorhinal/perirhinal, light blue bars) target structures performed similarly to sham operated control rats (white bars) on trained associations (BC, CD) and novel non-inferential probe trials (AE). However, lesioned rats were severely impaired on inferential probe trials (BD). Adapted by permission from Dusek and Eichenbaum (1997), copyright 1997 National Academy of Sciences, USA. (C) Mean performance of control participants (white bars), patients with hippocampal atrophy (blue bars) or Parkinson's disease patients (orange bars) in an acquired equivalence task. Patients with hippocampal atrophy reached a criterion level of performance at a rate similar to control participants. In contrast, Parkinson's disease patients required more extensive training. However, at test, hippocampal patients were severely impaired on inferential probe trials relative to both control participants and patients with Parkinson's disease. Adapted by permission from Myers et al. (2003), copyright 2003 MIT Press. (D) Post-training hippocampal lesions (blue bars) impaired transitive inference judgments (BD) in mice, but enhanced performance on novel non-inferential probe trials (AE) involving the end items of the hierarchy relative to sham operated animals (white bars). Adapted by permission from DeVito et al. (2010a), copyright 2009 Wiley-Liss, INC.

Figure 3

Symbolic depiction of encoding and retrieval strategies that may support inference.(A) Retrieval-based inference through recall and recombination of individual memories. When encountering a novel inferential probe (e.g., AC), the individual elements may trigger hippocampal pattern completion mechanisms, leading to the retrieval of the previously encountered overlapping associations (AB, BC) that can be then recombined to answer novel questions. In this example, when having to select which of the two men lives with the woman, one can recall that the woman lives in the red house, and that the man on the left also lives in the red house. Therefore, the woman lives with the man on the left. (B) Integration of overlapping events during encoding. When encountering an event that overlaps with prior experience (e.g., experiencing BC after encountering AB), the overlapping element (B) may trigger hippocampal pattern completion, reactivating the prior memory. The current experience may then be encoded in the context of the reactivated memory to form an integrated (A-B-C) representation that combines elements from both events. In this example, the prior memory for the woman living in the red house may be reactivated when learning about the man living in the same house. The current and reactivated experiences can then be combined to form a novel association that the man and the woman live together.

Figure 4

Hippocampal retrieval activation during inferential reasoning tasks.(A) Bilateral anterior hippocampus demonstrated selective activation during novel inferential probe trials (AC) at retrieval in an associative inference task. In contrast, a posterior region of the hippocampus demonstrated equivalent activation during associative retrieval of overlapping trained associations (AB, BC), non-overlapping trained associations (DE), and inferential probe trials. Adapted by permission from Preston et al. (2004), copyright 2004 Wiley-Liss, INC. (B) During transitive inference, left hippocampal activation demonstrated greater retrieval activation for novel inference trials relative to non-inference trials, while right hippocampus showed increased activation during inference trials in which items were separated by one element in the hierarchy (1°) compared with items separated by two hierarchical elements (2°). Adapted by permission from Zalesak and Heckers (2009), copyright 2009 Elsevier.

Figure 5

Hippocampal encoding activation during inferential reasoning tasks.(A) Left hippocampal activation increased across training block for inner pairs in the transitive hierarchy (B > C) relative to outer pairs (A > B), but only for those participants who were successful on the inferential test. Adapted by permission from Greene et al. (2006), copyright 2006 MIT Press. (B) In an associative inference task, right hippocampal activation during encoding of overlapping associations (BC) was greater for trials in which the corresponding inference judgment (AC) was later correct relative to trials on which the inference judgment was later incorrect. Hippocampal activation during initially acquired associations (AB) was not related to subsequent inferential performance. Adapted from Zeithamova and Preston (2010). (C) Activation in left and right hippocampus during the training phase of an acquired equivalence task was correlated with individual differences in inference performance. Specifically, increases in bilateral hippocampal activation from the early to late portion of the training phase were associated with superior performance on inferential probe trials. Adapted by permission from Shohamy and Wagner (2008), copyright 2008 Elsevier.

Figure 6

Schematic depiction of alternative accounts of hippocampal representation in an associative inference task. Representations of overlapping events (AB, BC) are shown using a simplified two-layer architecture. The bottom layer contains units for each event element; the top layer contains hypothesized patterns of hippocampal representation. (A) Single integrated representation for overlapping events. According to this hypothesized structure, new, overlapping event elements (C) are encoded into an existing, reactivated memory (AB) to form a single composite representation for the two related associations. (B) Pattern separated representations of individual events. In this view, a new event (BC) with partial overlap to a previous memory (AB) would recruit a distinct hippocampal representation that preserves the details of each individual experience. Links between the common element (B) and each of the individual experiences could be used to mediate inference at encoding or retrieval. (C) Relational representation of overlapping events. In this framework, separate representations are maintained for overlapping events (AB, BC) and direct links between those events (at the level of the hippocampus) code their relationship to one another.