Dramatic changes to well-known places go unnoticed.

How well do we know our city? It turns out, much more poorly than we might imagine. We used declarative memory and eye-tracking techniques to examine people's ability to detect modifications to real-world landmarks and scenes in Toronto locales with which they have had extensive experience. Participants were poor at identifying which scenes contained altered landmarks, whether the modification was to the landmarks' relative size, internal features, or relation to surrounding context. To determine whether an indirect measure would prove more sensitive, we tracked eye movements during viewing. Changes in overall visual exploration, but not to specific regions of change, were related to participants' explicit endorsement of scenes as modified. These results support the contention that very familiar landmarks are represented at a global or gist level, but not local or fine-grained, level. These findings offer a unified view of memory for gist across verbal and spatial domains, and across recent and remote memory, with implications for hippocampal-neocortical interactions.

Damage to the human dentate gyrus impairs the perceptual discrimination of complex, novel objects.

The hippocampus (HPC), and the dentate gyrus (DG) subregion in particular, is purported to be a pattern separator, orthogonally representing similar information so that distinct memories may be formed. The HPC may also be involved in complex perceptual discrimination. It is unclear if this role is limited to spatial/scene stimuli or extends to the discrimination of objects. Also unclear is whether the DG itself contributes to pattern separation beyond memory. BL, an individual with bilateral DG lesions, was previously shown to have poor discrimination of similar, everyday objects in memory. Here, we demonstrate that BL's deficit extends to complex perceptual discrimination of novel objects. Specifically, BL was presented with closely matched possible and impossible objects, which give rise to fundamentally different 3D perceptual representations despite being visually similar. BL performed significantly worse than controls when asked to select an odd object (e.g., impossible) amongst three identical counterpart objects (e.g., possible) presented at different rotations. His deficit was also evident in an atypical eye fixation pattern during this task. In contrast, BL's performance was indistinguishable from that of controls on other tasks involving the same objects, indicating that he could visually differentiate the object pairs, that he perceived the objects holistically in 3D, and that he has only a mild weakness in categorizing object possibility. Furthermore, his performance on standardized neuropsychological measures indicated intact mental rotation, visual-spatial attention, and working memory (visual and auditory). Collectively, these results provide evidence that the DG is necessary for complex perceptual discrimination of novel objects, indicating that the DG might function as a generic pattern separator of a wide range of stimuli within high-level perception, and that its role is not limited to memory.

Not only memory: Investigating the sensitivity and specificity of the Mnemonic Similarity Task in older adults.

Mnemonic discrimination, the process of distinguishing highly similar items in memory, relies on the dentate gyrus (DG) subregion of the hippocampus. The Mnemonic Similarity Task (MST) has been shown to be a sensitive behavioral measure of mnemonic discrimination that is in wide use (Liu et al., 2016). In this study, we evaluate the sensitivity and specificity of the MST in community-dwelling older adults who were administered the Montreal Cognitive Assessment (MoCA), a well-established screening measure for cognitive impairment. Using regression analyses, we tested a sample of 94 participants to determine whether MoCA overall score, MoCA score without the delayed recall subscale score, MoCA delayed recall subscale score, and MoCA status (MoCA score below or above the cut-off of 26/30) predicted MST lure discrimination performance. Regression models showed that all measures - except the MoCA delayed recall score - were significant predictors of MST lure discrimination performance. Our results support the sensitivity of the MST in detecting general cognitive decline but call into question the specificity of the MST with respect to memory and hippocampal function in a healthy older adult population.

Specifying the neural basis of the spacing effect with multivariate ERP.

The spacing effect refers to the finding that, given a fixed amount of study time, a longer interval between study repetitions improves long-term retention (e.g., Cepeda et al., 2006; Ebbinghaus, 1885/1967; Melton, 1970). Although the spacing effect is a robust and reliable finding in the memory literature, its cognitive and neural mechanisms remain unclear. We used event-related potentials (ERPs) to investigate the neural correlates of the spacing effect in the context of the study-phase retrieval hypothesis, which posits that repeated exposure of an item serves as a reminder of one's previous experience with the item, thereby promoting long-term retention. ERPs were recorded from 30 healthy young adults as they studied pairs of words under three levels of lag, corresponding to 0, 4, or 12 intervening pairs between the first and second occurrences of a target pair. We used two study-phase tasks that differed in the degree of retrieval that was required. During the test phase, participants were tested on paired-associate recall. The results demonstrated a significant effect of spacing on memory performance. However, the effect of encoding task and the interaction between encoding task and spacing were not significant. The results of the partial least squares analyses, which are not constrained by time window or electrode selection, revealed a spacing effect on the ERP data for both study-phase tasks; this effect occurred late in the epoch and was most salient over the centro-parietal scalp region. The results add to the literature on the neural correlates of the spacing effect by providing a more comprehensive account compared to past ERP findings that were focused on testing specific ERP components. They also call for further investigation on the various theoretical accounts of the spacing effect.

The spacing effect stands up to big data.

Many studies have shown that repetition of study material with temporal gaps between the repetitions (i.e., spaced in time) is more effective for long-term retention than are repetitions in immediate succession (i.e., massed; Greene, 1989). Although this spacing effect has proven to be robust in the laboratory (Cepeda, Pashler, Vul, Wixted, & Rohrer, 2006), its status in the real world is relatively understudied. Other research has demonstrated the benefit of memory retrieval on subsequent retrieval of the same information (Bjork, 1975, 1988; Roediger & Karpicke, 2006), referred to as the testing effect. However, it is not clear how spacing and retrieval can be optimally combined in order to enhance knowledge retention in a real-world setting. To investigate this question, we analyzed longitudinal data from 10,514 individuals, collected in the context of naturally occurring workplace training. To determine the impact of spaced retrieval on knowledge retention, these data were analyzed using a generalized linear mixed model with the following fixed factors: (1) spacing interval between repetitions of content training (retrieval practice), (2) retention interval, and (3) question format. Random factors included the specific content on which employees were trained, which was clustered by employee and, in turn, by company, resulting in a three-level hierarchy. The results showed a significant interaction between spacing interval and retention interval: the optimal amount of spacing between repeated retrieval events increased as the retention interval increased. These findings are in line with the results of laboratory studies, demonstrating the relevance and transferability of laboratory-based research to real-world contexts.

No evidence of risk-taking or impulsive behaviour in a person with episodic amnesia: Implications for the role of the hippocampus in future-regarding decision-making.

Does advantageous decision-making require one to explicitly remember the outcome of a series of past decisions or to imagine future personal consequences of one's choices? Findings that amnesic people with hippocampal damage cannot form a clear preference for advantageous decks over many learning trials on the Iowa Gambling Task (IGT) have been taken to suggest that complex decision-making on the IGT depends on declarative (episodic) memory and hippocampal integrity. Alternatively, impaired IGT performance in amnesic individuals could be secondary to risk-taking and/or impulsive behaviour resulting from impaired episodic future thinking (i.e. prospection) known to accompany amnesia. We tested this possibility in the amnesic individual K.C. using the IGT and the Toronto Gambling Task (TGT), a novel task that dissociates impulsivity from risk-taking without placing demands on declarative memory. K.C. did not develop a preference for advantageous over disadvantageous decks on the IGT and, instead, showed a slight preference for short-term gains and an inability to acquire a more adaptive appreciation of longer-term losses. He also did not display impulsive or risk-taking behaviour on the TGT, despite a profound inability to imagine personal future experiences. These findings suggest that impaired decision-making on the IGT in amnesia is unlikely to reflect a predilection to act in the moment or failure to take future consequences into account. Instead, some forms of future-regarding decision-making may be dissociable, with performance on tasks relying on declarative learning or on episodic-constructive processes more likely to be impaired.

Impaired event memory and recollection in a case of developmental amnesia.

A current debate in the literature is whether all declarative memories and associated memory processes rely on the same neural substrate. Here, we show that H.C., a developmental amnesic person with selective bilateral hippocampal volume loss, has a mild deficit in personal episodic memory, and a more pronounced deficit in public event memory; semantic memory for personal and general knowledge was unimpaired. This was accompanied by a subtle difference in impairment between recollection and familiarity on lab-based tests of recognition memory. Strikingly, H.C.'s recognition did not benefit from a levels-of-processing manipulation. Thus, not all types of declarative memory and related processes can exist independently of the hippocampus even if it is damaged early in life.

Deficits in past remembering extend to future imagining in a case of developmental amnesia.

Patient and neuroimaging studies report that the ability to remember past personal experiences and the ability to envision future personal experiences are interconnected. Loss of episodic memory is typically accompanied by loss of future imagining, and engaging in either activity recruits common brain areas. The relationship between episodic memory and future imagining is also suggested by their co-emergence in ontogenetic development. However, it is unknown whether a failure of one ability to emerge in early development precludes the development of the other ability. To investigate this possibility, we tested H.C., a young woman with amnesia of developmental origin associated with bilateral hippocampal loss, and demographically matched controls on an adapted version of the Autobiographical Interview using Galton-Crovitz cueing. In response to cue words, participants described both past personal events and imagined future personal events that occurred, or could occur, in near and distant time periods. Results indicated a parallel pattern of impairment for both past and future event generation in H.C., such that her narratives of both types of events were similarly deficient. These results indicate that mental time travel can be compromised in hippocampal amnesia, whether acquired in early or later life, possibly as a result of a deficit in reassembling and binding together details of stored information from earlier episodes.

New views on old memories: re-evaluating the role of the hippocampal complex.

Evidence of temporally graded retrograde amnesia (RA) following hippocampal damage has fuelled the long-standing belief that memory undergoes a consolidation process, whereby memories are progressively modified in neocortical regions until they are independent of the hippocampal (HPC) complex. Support for this position derives from both the animal and human RA literature, although the results are not consistent. Specifically, consolidation theory does not account for loss of episodic (detail) information in humans and context-dependent information in animals, which often extend back for much of the life span. We discuss an alternative approach, the Multiple Trace Theory, which suggests that the HPC complex contributes to the retrieval of recent and remote episodic and context-dependent memories. According to this view, such memory traces are represented as spatially distributed interactions between the HPC and neocortex that persist for as long as those memories exist. On the other hand, semantic, or context-free, memories can become independent of the HPC as consolidation theory predicts. In support of this view, we report recent accounts of relatively flat RA gradients in autobiographical and spatial detail loss in patients and animal models with extensive bilateral HPC lesions. By comparison, temporally graded RA was observed in tests of semantic and context-free memory. We also report neuroimaging studies in which hippocampal activity, elicited during recollection of autobiographical memories, did not distinguish recent from remote episodes. Our discussion suggests ways to reconcile discrepancies in the literature and guide predictions of the occurrence of flat versus temporally limited gradients of remote episodic and semantic memory loss following lesions to HPC.

Orofacial pain emerging as a dental specialty.

The emerging field of orofacial pain was considered by the American Dental Association for full status as a new dental specialty. While the recognition of orofacial pain as a specialty was denied, the American Academy of Orofacial Pain plans to continue its efforts. Many recent advances in the neuroscience of orofacial pain have led to treatments that provide significant relief for patients with chronic orofacial pain disorders. However, access to this care has been limited, leaving many patients to suffer. Dentists are generally supportive of the efforts to develop oral pain treatment into a specialty because the field will provide benefits for both dentists and their patients. A recent survey of 805 individuals who reported having a persistent pain disorder revealed that more than four out of 10 people have yet to find adequate relief, saying their pain is out of control--despite having the pain for more than five years and switching doctors at least once. "This survey suggests that there are millions of people living with severe uncontrolled pain," says Russell Portenoy, MD, president of the American Pain Society. "This is a great tragedy. Although not everyone can be helped, it is likely that most of these patients could benefit if provided with state-of-the-art therapies and improved access to pain specialists when needed." Development of the field of orofacial pain into a dental specialty has been moved primarily by the fact that historically, patients with complex chronic orofacial pain disorders have not been treated well by any discipline of healthcare. Recent studies of chronic orofacial pain patients have found that these patients have a higher number of previous clinicians and have endured many years with pain prior to seeing an orofacial pain dentist (see Figure 1). Complex pain patients and the clinicians who see them are often confused about who they should consult for relief of the pain. Treatment for those patients within the existing structure of dental or medical specialties has been inadequate, with millions of patients left suffering. Insurers are also confused with regard to reimbursement and may make decisions to exclude treatment for orofacial pain disorders under both dental and medical policies. However, dentistry has taken a leading role in healthcare to address the national problem of developing the field of orofacial pain into a dental specialty. A study of dentists and dental specialists has shown that there is a recognized need and broad support for developing this field into a specialty.

Remote spatial memory in an amnesic person with extensive bilateral hippocampal lesions.

The hippocampus may have a time-limited role in memory, being needed only until information is permanently stored elsewhere, or this region may permanently represent long-term allocentric spatial information or cognitive maps in memory. To test these ideas, we investigated remote spatial memory in K.C., a patient with bilateral hippocampal lesions and amnesia for autobiographical events. In his spatial knowledge, general aspects were preserved, but details were lost, a pattern that resembled his memory loss in other domains. K.C. performed normally on allocentric spatial tests of his neighborhood and the world. He had difficulty, however, in recognizing and identifying non-salient neighborhood landmarks, and in recognizing city locations on world maps. This suggests that the hippocampus is not crucial for maintenance and retrieval of remotely formed spatial representations of major landmarks, routes, distances and directions, but is necessary for specifying location details, regardless of when they were acquired.

Intravesical bacille Calmette-Guérin therapy for muscle invasive bladder cancer.

OBJECTIVES: This investigation attempted to determine whether the degree of fibronectin expression in the bladders of patients with invasive transitional cell carcinoma correlated with their clinical response to intravesical bacille Calmette-Guerin (BCG) therapy. METHODS: Following transurethral resection of all invasive disease, 13 patients with Stages T2-T4 bladder cancer were administered intravesical BCG (fo 6 weeks followed by monthly instillations). Fibronectin expression in the patients' resected tumors and normal mucosa was determined by immunohistochemical staining techniques. Minimum disease-free follow-up was 60 months. RESULTS: Only 1 of 13 patients had neither local nor systemic disease recurrence; 10 of 13 patients developed systemic disease and 7 patients died from metastases. Fibronectin expression was not correlated with the clinical response to BCG. CONCLUSIONS: Intravesical BCG therapy for the treatment of muscle invasive transitional cell carcinoma of the bladder is ineffective. Fibronectin expression in the bladder of patients with invasive disease is variable and does not correlate significantly with the clinical response to BCG therapy.

The possible effect of periodontal diseases on occlusal function.

This paper raises new questions about the relationship between occlusion and periodontics. Specifically, it raises questions about the effect of periodontal diseases on mechanoreceptors in the periodontal ligament. Periodontal mechanoreceptors transmit information from the periodontium to various reflexes coordinated by the central nervous system. One of these reflexes is the trigemino-neck reflex. Its function is to change the position of the head, neck, and jaws on a moment-to-moment basis, and it powerfully influences the occlusal position. This paper raises questions about the consequences of periodontal diseases on all reflexes that depend on periodontal mechanoreceptors, and specific questions are raised about the effect of periodontal disease on the trigemino-neck reflex because of its extreme importance to the way we analyze and treat occlusion.