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.

Simple probabilistic reinforcement learning is recognized as a striatum-based learning system, but in recent years, has also been associated with hippocampal involvement. This study examined whether such involvement may be attributed to observation-based learning (OL) processes, running in parallel to striatum-based reinforcement learning. A computational model of OL, mirroring classic models of reinforcement-based learning (RL), was constructed and applied to the neuroimaging data set of Palombo, Hayes, Reid, and Verfaellie [2019. Hippocampal contributions to value-based learning: Converging evidence from fMRI and amnesia. Cognitive, Affective & Behavioral Neuroscience , 19 (3), 523–536]. Results suggested that OL processes may indeed take place concomitantly to reinforcement learning and involve activation of the hippocampus and central orbitofrontal cortex. However, rather than independent mechanisms running in parallel, the brain correlates of the OL and RL prediction errors indicated collaboration between systems, with direct implication of the hippocampus in computations of the discrepancy between the expected and actual reinforcing values of actions. These findings are consistent with previous accounts of a role for the hippocampus in encoding the strength of observed stimulus–outcome associations, with updating of such associations through striatal reinforcement-based computations. In addition, enhanced negative RL prediction error signaling was found in the anterior insula with greater use of OL over RL processes. This result may suggest an additional mode of collaboration between the OL and RL systems, implicating the error monitoring network.

Recent interest in the role of the hippocampus in temporal aspects of cognition has been fueled, in part, by the observation of “time” cells in the rodent hippocampus—that is, cells that have differential firing patterns depending on how long ago an event occurred. Such cells are thought to provide an internal representation of elapsed time. Yet, the hippocampus is not needed for processing temporal duration information per se, at least on the order of seconds, as evidenced by intact duration judgments in rodents and humans with hippocampal damage. Rather, it has been proposed that the hippocampus may be essential for coding higher order aspects of temporal mnemonic processing, such as those needed to temporally organize a sequence of events that form an episode. To examine whether (1) the hippocampus uses duration information in the service of establishing temporal relations among events and (2) its role in memory for duration is unique to sequences, we tested amnesic patients with medial-temporal lobe damage (including the hippocampus). We hypothesized that medial-temporal lobe damage should impair the ability to remember sequential duration information but leave intact judgments about duration devoid of a sequential demand. We found that amnesics were impaired in making judgments about durations within a sequence but not in judging single durations. This impairment was not due to higher cognitive load associated with duration judgments about sequences. In convergence with rodent and human fMRI work, these findings shed light on how time coding in the hippocampus may contribute to temporal cognition.

Medial-temporal lobe (MTL) lesions are associated with severe impairments in episodic memory. In the framework of the temporal context model, the hypothesized mechanism for episodic memory is the reinstatement of a prior experienced context (i.e., “jump back in time”), which relies upon the MTL [Howard, M. W., Fotedar, M. S., Datey, A. V., & Hasselmo, M. E. The temporal context model in spatial navigation and relational learning: Toward a common explanation of medial temporal lobe function across domains. Psychological Review, 112, 75–116, 2005]. This hypothesis has proven difficult to test in amnesia because of the floor-level performance by patients in recall tasks. To circumvent this issue, in this study, we used a “looped-list” format, in which a set of verbal stimuli was presented multiple times in a consistent order. This allowed for comparison of statistical properties such as probability of first recall and lag-conditional response probability (lag-CRP) between amnesic patients and healthy controls. Results revealed that the lag-CRP, but not the probability of first recall, is altered in amnesia, suggesting a selective disruption of temporal contiguity. To further characterize the results, we fit a scale-invariant version of the temporal context model [Howard, M. W., Shankar, K. H., Aue, W. R., & Criss, A. H. A distributed representation of internal time. Psychological Review, 122, 24–53, 2015] to the probability of first recall and lag-CRP curves. The modeling results suggested that the deficit in temporal contiguity in amnesia is best described as a failure to recover temporal context. These results provide the first direct evidence for an impairment in a jump-back-in-time mechanism in patients with MTL amnesia.

We evaluated whether prior semantic knowledge would enhance episodic learning in amnesia. Subjects studied prices that are either congruent or incongruent with prior price knowledge for grocery and household items and then performed a forced-choice recognition test for the studied prices. Consistent with a previous report, healthy controls' performance was enhanced by price knowledge congruency; however, only a subset of amnesic patients experienced the same benefit. Whereas patients with relatively intact semantic systems, as measured by an anatomical measure (i.e., lesion involvement of anterior and lateral temporal lobes), experienced a significant congruency benefit, patients with compromised semantic systems did not experience a congruency benefit. Our findings suggest that when prior knowledge structures are intact, they can support acquisition of new episodic information by providing frameworks into which such information can be incorporated.

The issue of whether the hippocampus and related structures in the medial-temporal lobe (MTL) play a temporary or permanent role in autobiographical episodic memory remains unresolved. One long-standing belief is that autobiographical memory (AM), like semantic memory, is initially dependent on the MTL but ultimately can be retained and recovered independently of it. However, evidence that hippocampal amnesia results in severe loss of episodic memory for a lifetime of personally experienced events suggests otherwise. To test the opposing views, we conducted detailed investigations of autobiographical episodic memory in people with amnesia resulting from MTL lesions of varying extent. By combining precise quantification of MTL and neocortical volumes with sensitive measures of recollection of one's personal past, we show that the severity of episodic, but not semantic, AM loss is best accounted for by the degree of hippocampal damage and less likely related to additional neocortical compromise.

The transverse patterning (TP) task (A+ B−, B+ C−, C+ A−) has played a central role in testing the hypothesis that medial-temporal (and, in particular, hippocampal) brain damage selectively impairs learning on at least some classes of configural (i.e., nonlinear) learning tasks. Results in the animal and human literature generally support that hypothesis. Reed and Squire [Impaired transverse patterning in human amnesia is a special case of impaired memory for two-choice discrimination tasks. Behavioral Neuroscience, 113 , 3–9, 1999], however, advanced an alternative account in which impaired TP performance in amnesia reflects a generic scaling artifact arising from the greater difficulty of the TP task compared to the elemental (i.e., linear) control task that is typically used. We begin with a critique of Reed and Squire, countering their conceptual arguments and showing that their results, when analyzed appropriately, support the configural deficit hypothesis. We then report results from eight new amnesic patients and controls on an improved version of the TP task. Despite substantial practice, accuracy of patients with bilateral hippocampal damage due to anoxia reached and maintained an asymptote of only 54% correct, well below the maximum accuracy obtainable (67%) in the absence of configural learning. A patient with selective bilateral damage to the anterior thalamic nuclei exhibited a TP accuracy asymptote that was near 67%, a pattern of two out of three correct consecutive trials, and a pattern of nearly always answering correctly for two of the three TP item pairs. These results are consistent with a set of unique and parameter-free predictions of the configural deficit hypothesis.

Making judgments about the retrievability of information is a critical part of the metamemory processes engaged during remembering. A recent study of patients with frontal lesions suggests that ventral medial prefrontal cortex (VMPC) plays a critical role in such judgments [Schnyer, D. M., Verfaellie, M., Alexander, M. P., Lafleche, G., Nicholls, L., & Kaszniak, A. W. A role for right medial prefrontal cortex in accurate feeling of knowing judgments: Evidence from patients with lesions to frontal cortex. Neuropsychologia, 42, 957–966, 2004]. The observed impairment was thought to reflect an inability to determine the accessibility of memory contents. To further examine the neuroanatomical basis of content accessibility assessment, we used fMRI in an episodic feeling-of-knowing (FOK) paradigm. Participants were asked to make trial-by-trial predictions about the retrievability of the final word that completed studied sentences and then to select the correct completion from among alternatives. Results indicated that the VMPC is engaged during accurate FOK judgments and its activation is modulated by retrieval rating. Structural equations modeling supported the notion that VMPC, as part of a broader left hemisphere network involved in memory retrieval, monitors the output of the retrieval process. More generally, VMPC may participate in metacognitive processes that allow for the comparison of available data against an internal model.

False recognition occurs when people mistakenly claim that a novel item is familiar. After studying lists of semantically related words, healthy controls show extraordinarily high levels of false recognition to nonstudied lures that are semantic associates of study list words. In previous experiments, we found that both Korsakoff and non-Korsakoff amnesic patients show reduced levels of false recognition to semantic associates, implying that the medial temporal/diencephalic structures that are damaged in amnesic patients are involved in the encoding and/or retrieval of information that underlies false recognition. These data contrast with earlier results indicating greater false recognition in Korsakoff amnesics than in control subjects. The present experiment tests the hypothesis that greater or lesser false recognition of semantic associates in amnesic patients, relative to normal controls, can be demonstrated by creating conditions that are more or less conducive to allowing true recognition to suppress false recognition. With repeated presentation and testing of lists of semantic associates, control subjects and both Korsakoff and non-Korsakoff amnesics showed increasing levels of true recognition across trials. However, control subjects exhibited decreasing levels of false recognition across trials, whereas Korsakoff amnesic patients showed increases across trials and non-Korsakoff amnesics showed a fluctuating pattern. Consideration of signal detection analyses and differences between the two types of amnesic patients provides insight into how mechanisms of veridical episodic memory can be used to suppress false recognition.

Two sets of experiments, each consisting of a semantic priming task and a discrimination task, investigated the proceedings of lexical information in the neglected visual field. In the semantic priming task, subjects made lexical decisions to target words preceded by lateralized word primes; in the discrimination task, they indicated which of two words corresponded to a target word presented to the left visual field (LVF) or right visual field (RVF). The first set of experiments indicated that although patients were unable to discriminate words presented in the LVF, they showed significant priming when LVF primes were followed by semantically related targets compared to unrelated targets. The second set of experiments further examined the nature of this priming effect by comparing priming in a condition in which primes were semantically related to the target word (e.g., TEA-CUP) and a condition in which primes were unrelated to the target word, but orthographically similar to a related prime (e.g., PEA-CUP). This experiment replicated the previously established semantic priming effects and demonstrated significant negative priming for targets preceded by LVF primes that were orthographically similar to a semantically related word. Again, patients performed at chance in the forced-choice discrimination task when targets were presented in the LVF These findings indicate that semantic processing of neglected lexical information is based on fully specified perceptual and orthographic information. A lateral inhibitory mechanism is proposed that maximizes the probability, albeit unsuccessfully, that neglected orthographic information will reach awareness.