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Theoretical accounts of moral decision making imply distinct ways in which episodic memory processes may contribute to judgments about moral dilemmas that entail high conflict between a harmful action and a greater good resulting from such action. Yet, studies examining the status of moral judgment in amnesic patients with medial temporal lobe (MTL) lesions have yielded inconsistent results. To examine whether and how episodic processes contribute to high conflict moral decisions, amnesic patients with MTL damage and control participants were asked to judge the moral acceptability of a harmful action across two conditions that differed in the framing of the moral question. We predicted that personal (but not abstract) framing would engage episodic processes involved in mental simulation, yielding a selective impairment in MTL patients in the personal framing condition. This prediction was not confirmed as neither patients nor controls were influenced by the framing of the moral question. With the exception of a patient whose lesion extended into the amygdala bilaterally, patients were less willing than controls to endorse the utilitarian option, rejecting the harmful action despite its beneficial outcome. They also rated actions as emotionally more intense than did controls. These findings suggest that episodic processes involved in mental simulation are necessary to prospectively evaluate action-outcome contingencies., (© 2021 This article is a U.S. Government work and is in the public domain in the USA.)

A prevailing view in cognitive neuroscience suggests that different forms of learning are mediated by dissociable memory systems, with a mesolimbic (i.e., midbrain and basal ganglia) system supporting incremental trial-and-error reinforcement learning and a hippocampal-based system supporting episodic memory. Yet, growing evidence suggests that the hippocampus may also be important for trial-and-error learning, particularly value or reward-based learning. In the present report, we use a lesion-based neuropsychological approach to clarify hippocampal contributions to such learning. Six amnesic patients with medial temporal lobe damage and a group of healthy controls were administered a simple value-based learning task involving probabilistic trial-and-error acquisition of stimulus-response-outcome (reward or none) contingencies modeled after Li et al. (Proceedings of the National Academy of Sciences , 2011, 108 (1), 55-60). As predicted, patients were significantly impaired on the task, demonstrating reduced learning of the contingencies. Our results provide further supportive evidence that the hippocampus' role in cognition extends beyond episodic memory tasks and call for further refinement of theoretical models of hippocampal functioning., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

During sleep, the hippocampus plays an active role in consolidating memories that depend on it for initial encoding. There are hints in the literature that the hippocampus may have a broader influence, contributing to the consolidation of memories that may not initially require the area. We tested this possibility by evaluating learning and consolidation of the motor sequence task (MST) in hippocampal amnesics and demographically matched control participants. While the groups showed similar initial learning, only controls exhibited evidence of overnight consolidation. These results demonstrate that the hippocampus can be required for normal consolidation of a task without being required for its acquisition, suggesting that the area plays a broader role in coordinating memory consolidation than has previously been assumed., (© 2019 Wiley Periodicals, Inc.)

In the present study, we examined the role of the medial temporal lobe (MTL) in prospective time estimation at short and long timescales using a novel behavioral paradigm adapted from rodent work. Amnesic patients with MTL damage and healthy control participants estimated the duration of nature-based video clips that were either short (≤ 90 s) or long (more than 4 min). Consistent with previous work in rodents, we found that amnesic patients were impaired at making estimations for long, but not for short durations. Critically, these effects were observed in patients who had lesions circumscribed to the hippocampus, suggesting that the pattern observed was not attributable to the involvement of extra-hippocampal structures. That the MTL, and more specifically the hippocampus, is critical for prospective temporal estimation only at long intervals suggests that multiple neurobiological mechanisms support prospective time estimation., (© 2015 Wiley Periodicals, Inc.)

Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no--TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI--LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no--TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS., (Published 2015. This article is a U.S. Government work and is in the public domain in the USA.)

In the present study, we investigated the effect of medial temporal lobe (MTL) damage on human decision making in the context of reward-based intertemporal choice. During intertemporal choice, humans typically devalue (or discount) a future reward to account for its delayed arrival (e.g., preferring $30 now over $42 in 2 months), but this effect is attenuated when participants engage in episodic future thinking, i.e., project themselves into the future to imagine a specific event. We hypothesized that this attenuation would be selectively impaired in amnesic patients, who have deficits in episodic future thinking. Replicating previous work, in a standard intertemporal choice task, amnesic patients showed temporal discounting indices similar to healthy controls. Consistent with our hypothesis, while healthy controls demonstrated attenuated temporal discounting in a condition that required participants first to engage in episodic future thinking (e.g., to imagine spending $42 at a theatre in 2 months), amnesic patients failed to demonstrate this effect. Moreover, as expected, amnesic patients' narratives were less episodically rich than those of controls. These findings extend the range of tasks that are shown to be MTL dependent to include not only memory-based decision-making tasks but also future-oriented ones., (© 2014 Wiley Periodicals, Inc.)

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., (Copyright © 2012 Wiley Periodicals, Inc.)

Neuroscientific research has shown that the hippocampus is important for binding or linking together the various components of a learning event into an integrated memory. In a prior study, we demonstrated that the anterior hippocampus is involved in memory for the relations among informational elements to a greater extent that it is involved in memory for individual elements (Giovanello et al., 2004. Hippocampus 14:5-8). In the current study, we extend those findings by further specifying the role of anterior hippocampus during relational memory retrieval. Specifically, anterior hippocampal activity was observed during flexible retrieval of learned associations, whereas posterior hippocampal activity was detected during reinstatement of study episodes. These findings suggest a functional dissociation across the long axis of human hippocampus based on the nature of the mnemonic process rather than the stage of memory processing or type of stimulus.

Behavioral studies with amnesic patients and imaging studies with healthy adults have suggested that medial temporal lobe (MTL) structures known to be essential for long-term declarative memory (LTM) may also be involved in the maintenance of information in working memory (WM). To examine whether MTL structures are involved in WM maintenance for faces, and the nature of that involvement, WM and LTM for faces were examined in normal participants via functional magnetic resonance imaging (fMRI) and in amnesic patients behaviorally. In Experiment 1, participants were scanned while performing a WM task in which they determined if two novel faces, presented 7 s apart, were the same or different. Later, participants' LTM for the faces they saw during the WM task was measured in an unexpected recognition test. During WM maintenance, the hippocampus was activated bilaterally, and there was greater activation during maintenance for faces that were later remembered than faces later forgotten. A conjunction analysis revealed overlap in hippocampal activations across WM maintenance and LTM contrasts, which suggested that the same regions were recruited for WM maintenance and LTM encoding. In Experiment 2, amnesic and control participants were tested on similar WM and LTM tasks. Amnesic patients, as a group, had intact performance with a 1-s maintenance period, but were impaired after a 7-s WM maintenance period and on the LTM task. Thus, parallel neuroimaging and lesion designs suggest that the same hippocampal processes support WM maintenance, for intervals as short as 7 s, and LTM for faces., (Copyright 2006 Wiley-Liss, Inc.)

Neuroscientific research has established that the hippocampal formation, a structure within the medial temporal lobe (MTL), plays a critical role in memory for facts and events (declarative memory) (Milner et al., 1998). However, its precise role remains unclear. According to one view, the hippocampus has a special role in relating or binding together previously unrelated pieces of information, while another view proposes that the hippocampus is equally involved in all forms of declarative memory, regardless of their demands on relational processing. Using functional magnetic resonance imaging (fMRI), we show that hippocampal activation is modulated by the extent to which a retrieval task depends on relational processing.