Role In Declarative Memory Research Articles

Prediction of declarative memory profile in panic disorder patients: a machine learning-based approach.

To develop a classification framework based on random forest (RF) modeling to outline the declarative memory profile of patients with panic disorder (PD) compared to a healthy control sample. We developed RF models to classify the declarative memory profile of PD patients in comparison to a healthy control sample using the Rey Auditory Verbal Learning Test (RAVLT). For this study, a total of 299 patients with PD living in the city of Rio de Janeiro (70.9% females, age 39.9 ± 7.3 years old) were recruited through clinician referrals or self/family referrals. Our RF models successfully predicted declarative memory profiles in patients with PD based on RAVLT scores (lowest area under the curve [AUC] of 0.979, for classification; highest root mean squared percentage [RMSPE] of 17.2%, for regression) using relatively bias-free clinical data, such as sex, age, and body mass index (BMI). Our findings also suggested that BMI, used as a proxy for diet and exercises habits, plays an important role in declarative memory. Our framework can be extended and used as a prospective tool to classify and examine associations between clinical features and declarative memory in PD patients.

Commentary on Otto Kernberg’s “some implications of new developments in neurobiology for psychoanalytic object relations theory”

ABSTRACT Otto Kernberg reaffirms the central motivational role of affects in his object relations theory by incorporating the seminal work of Jaak Panksepp’s affective neuroscience. At the same time, he retains a dual drive model that posits libido and aggression as both a supraordinate level of development and etiologic of all unconscious conflict. The neuroscience he relies upon suggests alternative perspectives. Kernberg’s dynamic unconscious postulates the essential role of declarative memory regarding the neurotic use of repression and the more primitive dissociative defenses in sicker patients. This view is compared to that of Mucci, who sees dissociation as procedural memory. I suggest a broader conceptualization of the dynamic unconscious that takes into account, as Kernberg states, its infantile origins and incorporates the nonverbal symbolic realm of experience.

Who Are You? The Study of Personality in Patients With Anterograde Amnesia

Little is known about the role of declarative memory in the ongoing perception of one’s personality. Seven individuals who developed a rare and severe type of anterograde amnesia following damage to their medial temporal lobes were identified from our neurological patient registry. We examined the stability of their personality ratings on the Big Five Inventory over five retest periods and assessed the accuracy of their ratings via analyses of self–caregiver agreement. The patients portrayed a stable sense of self over the course of 1 year. However, their self-ratings differed from those provided by the caregivers. Intriguingly, these discrepancies diminished when caregivers retrospectively rated the patients’ personalities prior to their brain injury, suggesting that patients’ perceptions of themselves were stuck in the past. We interpret our findings to indicate that the ability to form new declarative memories is not required for maintaining a stable sense of self but may be important for updating one’s sense of self over time.

Role of the hippocampal CA1 region in incremental value learning

It is generally believed that the hippocampus plays a crucial role in declarative memory—remembering facts and events—but not in gradual stimulus-response association or incremental value learning. Based on the finding that CA1 conveys strong value signals during dynamic foraging, we investigated the possibility that the hippocampus contributes to incremental value learning. Specifically, we examined effects of inactivating different subregions of the dorsal hippocampus on behavioral performance of mice performing a dynamic foraging task in a modified T-maze. A reinforcement learning model-based analysis indicated that inactivation of CA1, but not dentate gyrus, CA3, or CA2, impaired trial-by-trial updating of chosen value without affecting value-dependent action selection. As a result, it took longer for CA1-inactivated mice to bias their choices toward the higher-reward-probability target after changes in reward probability. Our results indicate, contrary to the traditional view, that the hippocampus, especially CA1, might contribute to incremental value learning under certain circumstances.

Slow wave sleep and accelerated forgetting

We investigated whether the benefit of slow wave sleep (SWS) for memory consolidation typically observed in healthy individuals is disrupted in people with accelerated long-term forgetting (ALF) due to epilepsy. SWS is thought to play an active role in declarative memory in healthy individuals and, furthermore, electrographic epileptiform activity is often more prevalent during SWS than during wakefulness or other sleep stages. We studied the relationship between SWS and the benefit of sleep for memory retention using a word-pair associates task. In both the ALF and the healthy control groups, sleep conferred a memory benefit. However, the relationship between the amount of SWS and sleep-related memory benefits differed significantly between the groups. In healthy participants, the amount of SWS correlated positively with sleep-related memory benefits. In stark contrast, the more SWS, the smaller the sleep-related memory benefit in the ALF group. Therefore, contrary to its role in healthy people, SWS-associated brain activity appears to be deleterious for memory in patients with ALF.

Effects of dividing attention on memory for declarative and procedural aspects of tool use.

Tool-related knowledge and skills are supported by a complex set of memory processes that are not well understood. Some aspects of tools are mediated by either declarative or procedural memory, while other aspects may rely on an interaction of both systems. Although motor skill learning is believed to be primarily supported by procedural memory, there is debate in the current literature regarding the role of declarative memory. Growing evidence suggests that declarative memory may be involved during early stages of motor skill learning, although findings have been mixed. In the current experiment, healthy, younger adults were trained to use a set of novel complex tools and were tested on their memory for various aspects of the tools. Declarative memory encoding was interrupted by dividing attention during training. Findings showed that dividing attention during training was detrimental for subsequent memory for tool attributes as well as accurate demonstration of tool use and tool grasping. However, dividing attention did not interfere with motor skill learning, suggesting that declarative memory is not essential for skill learning associated with tools.

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens

IntroductionDeep brain stimulation (DBS) is a circuit-based treatment shown to relieve symptoms from multiple neurologic and neuropsychiatric disorders. In order to treat the memory deficit associated with Alzheimer's disease (AD), several clinical trials have tested the efficacy of DBS near the fornix. Early results from these studies indicated that patients who received fornix DBS experienced an improvement in memory and quality of life, yet the mechanisms behind this effect remain controversial. It is known that transmission between the medial limbic and corticolimbic circuits plays an integral role in declarative memory, and dysfunction at the circuit level results in various forms of dementia, including AD. Here, we aimed to determine the potential underlying mechanism of fornix DBS by examining the functional circuitry and brain structures engaged by fornix DBS. MethodsA multimodal approach was employed to examine global and local temporal changes that occur in an anesthetized swine model of fornix DBS. Changes in global functional activity were measured by functional MRI (fMRI), and local neurochemical changes were monitored by fast scan cyclic voltammetry (FSCV) during electrical stimulation of the fornix. Additionally, intracranial microinfusions into the nucleus accumbens (NAc) were performed to investigate the global activity changes that occur with dopamine and glutamate receptor-specific antagonism. ResultsHemodynamic responses in both medial limbic and corticolimbic circuits measured by fMRI were induced by fornix DBS. Additionally, fornix DBS resulted in increases in dopamine oxidation current (corresponding to dopamine efflux) monitored by FSCV in the NAc. Finally, fornix DBS-evoked hemodynamic responses in the amygdala and hippocampus decreased following dopamine and glutamate receptor antagonism in the NAc. ConclusionsThe present findings suggest that fornix DBS modulates dopamine release on presynaptic dopaminergic terminals in the NAc, involving excitatory glutamatergic input, and that the medial limbic and corticolimbic circuits interact in a functional loop.

Memory and Space: Towards an Understanding of the Cognitive Map.

Research of hippocampal function is dominated by two major views. The spatial view argues that the hippocampus tracks routes through space, whereas the memory view suggests a broad role in declarative memory. Both views rely on considerable evidence, but neither provides a complete account of hippocampal function. Here we review evidence that, in addition to spatial context, the hippocampus encodes a wide variety of information about temporal and situational context, about the systematic organization of events in abstract space, and about routes through maps of cognition and space. We argue that these findings cross the boundaries of the memory and spatial views and offer new insights into hippocampal function as a system supporting a broad range of cognitive maps.

Single-cell recordings in the human medial temporal lobe.

Recordings from individual neurons in patients who are implanted with depth electrodes for clinical reasons have opened the possibility to narrow down the gap between neurophysiological studies in animals and non-invasive (e.g. functional magnetic resonance imaging, electroencephalogram, magnetoencephalography) investigations in humans. Here we provide a description of the main procedures for electrode implantation and recordings, the experimental paradigms used and the main steps for processing the data. We also present key characteristics of the so-called ‘concept cells’, neurons in the human medial temporal lobe with selective and invariant responses that represent the meaning of the stimulus, and discuss their proposed role in declarative memory. Finally, we present novel results dealing with the stability of the representation given by these neurons, by studying the effect of stimulus repetition in the strength of the responses. In particular, we show that, after an initial decay, the response strength reaches an asymptotic value after approximately 15 presentations that remains above baseline for the whole duration of the experiment.

Impaired Hippocampal Theta Oscillations in the Mice Null Alpha7 Nicotinic Acetylcholine Receptors

Nicotinic acetylcholine receptor (nAChR) a7 subunits are among the most ancient of vertebrate nAChR subunits and have the capacity to assemble as homomers. Naturally expressed a7-nAChRs in the central nervous system play a critical role in modulating the release of various neurotransmitters, neurite outgrowth, and even neuronal survival or death [1]. a7-nAChRs also have been implicated in development, differentiation, and disease of the nervous system, as well as being targets of nicotine action. a7-nAChRs are highly expressed in the hippocampus, a brain structure associated to learning, memory, and cognitive functions. Accumulating lines of evidence demonstrate that a7-nAChRs are key targets in mediating cholinergic modulations of cognition [2]. Hippocampus plays an important role in declarative memory and learning, and possesses a large amplitude rhythm at theta frequency (4–12 Hz), which is postulated to support mnemonic processes in humans and rodents [3,4]. It has been reported that nicotine modulates hippocampal theta oscillations likely through a4b2-nAChRs [5,6], but the role of a7-nAChRs in hippocampal theta oscillations is still uncertain. Whether or not a7-nAChR knockout (KO) mice exhibit hippocampal theta oscillation is unknown. Here, we present, for the first time, that a7-nAChR KO mice selectively lack hippocampal theta oscillations. All experimental procedures were approved by the Institutional Animal Care and Use Committee at the Barrow Neurological Institute. The data were collected from 27 hippocampal slices from 8 wild-type (WT) mice (postnatal 28 3 days) and 16 hippocampal slices from 6 a7-nAChR KOmice (postnatal 26 3 days, P > 0.05 between WT and a7-nAChR KO mice, t-test). Transverse hippocampal slices (450 lm) were prepared as previously reported [7]. External solution contained (mM) NaCl 124, NaHCO3 26, KCl 3, KH2PO4 1.2, CaCl2 2.4, MgSO4 1.3, D-glucose 10, which was continuously bubbled with 95% O2–5% CO2 during the entire experimental period. Field potential recordings were performed in the CA1 cell layer using a glass electrode filled with 2 M NaCl. During recordings, the recording chamber was set to 31°C. Hippocampal theta oscillations were induced by bath application of 50 lM carbachol (CCh) for 50–60 min, as previously described [5,8]. Under this experimental protocol, only one slice showed no response to CCh in 27 tested slices from WT mice, while six slices showed no response to CCh in 16 tested slices from a7-nAChR KO mice. As shown in Figure 1, in the continuous presence of 50 lM CCh, there were typically three types of oscillations, slow (delta: 0.5 0.06 Hz, n = 18), theta (6.3 0.46 Hz, n = 23), and super-fast (146.1 7.0 Hz, n = 19) oscillations in WT hippocampal slices (Figure 1A). However, in a7-nAChR KO hippocampal

Dorsal hippocampal lesions boost performance in the rat sequential reaction time task

It is commonly accepted that the hippocampus plays a major role in declarative memory across species and that it is of particular relevance for spatial memory in rodents. However, the interplay between hippocampal function and nondeclarative memory systems, such as procedural stimulus-response (S-R) or sequential learning, is less clear: depending on task requirements, an interaction, dissociation or interference between hippocampal function and other memory systems may occur. This study was conducted to investigate the influence of dorsal ibotenic hippocampal lesions on learning and performance of sequential behavior in a rat version of the serial reaction time task (SRTT). Magnetic resonance imaging (MRI) analyses of the lesions revealed a bilateral volume reduction of ≈ 46% (histological analyses: ≈ 59%) of the total hippocampus. They were largely confined to its dorsal part and led to an expected spatial memory deficits in an object place recognition test as compared to healthy controls, even though sham lesions had the same effect. Our earlier studies on sequential learning had revealed substantial impairments in case of dorsal striatal dopaminergic lesions. In the present study, however, hippocampal lesioned animals unexpectedly showed superior performance throughout SRTT testing and training as compared to controls, which resulted in a higher degree of subsequent automated sequential behavior. Thus, our data reveal the infrequent case where hippocampal lesions lead to long-term improvements in test performance of a type of rather complex procedural behavior. One possible explanation for this effect is that hippocampal activity in rodents can interfere with other memory systems during the acquisition of procedural tasks with very low spatial requirements, as used here. Alternative explanations for the observed superior SRTT performance in lesioned animals, such as hyperactivity or increased exploratory drive are also topic of the discussion.

Hippocampal function, declarative memory, and schizophrenia: Anatomic and functional neuroimaging considerations

Introduction Memory permits an organism to bridge the past with the present, providing information about prior encounters with a stimulus or context that can serve to build predictive models for the present. At the neurobiologic level, it is well established that the hippocampus and surrounding medial temporal lobe (MTL) cortices play an essential role in declarative memory (ie, long-term memory for general facts and specific events) [1–5]. The MTL memory circuit is composed of multiple structures, including the hippocampal formation and the surrounding entorhinal, perirhinal, and parahippocampal cortices. The hippocampal formation is further composed of the dentate gyrus, the fields of the cornu Ammonis (CA), and subiculum. Recent investigations of MTL processing have sought to characterize the mnemonic function of specific MTL substructures. Hypotheses regarding functional segregation within the MTL have largely focused on the hierarchical connectivity of the region, emphasizing potential functional differences between the hippocampus and surrounding cortices [6–8]. Recent studies have also explored potential functional distinctions between substructures within the hippocampus, such as CA3 and subiculum [7–10]. Hypotheses regarding the functions of MTL substructures draw heavily on knowledge of the anatomic connectivity of the region with structures in neocortex, as well as information about the intrinsic connectivity within MTL. Such anatomically guided hypotheses may prove particularly insightful when investigating disease processes that affect MTL. Schizophrenia is associated with memory impairments together with abnormalities in specific hippocampal substructures [11–14]. In particular, schizophrenic patients are impaired on declarative memory tasks [13,15], and functional neuroimaging studies have begun to reveal correlated hippocampal abnormalities. The present commentary reviews recent functional neuroimaging data regarding MTL function in the healthy brain and in schizophrenia. These initial observations are placed within the context of knowledge about projections to and within the MTL circuit, as anatomically informed models are likely to facilitate understanding of diseaserelated MTL dysfunction, potentially pointing to new avenues for intervention.

The Perceptual-Mnemonic/Feature Conjunction Model of Perirhinal Cortex Function

The perirhinal cortex was once thought to be "silent cortex", virtually ignored by researchers interested in the neurobiology of learning and memory. Following studies of brain damage associated with cases of amnesia, perirhinal cortex is now widely regarded as part of a "medial temporal lobe (MTL) memory system". This system is thought to be more or less functionally homogeneous, having a special role in declarative memory, and making little or no contribution to other functions such as perception. In the present article, we summarize an alternative view. First, we propose that components of the putative MTL system such as the hippocampus and perirhinal cortex have distinct and dissociable functions. Second, we provide evidence that the perirhinal cortex has a role in visual discrimination. In addition, we propose a specific role for perirhinal cortex in visual discrimination: the contribution of complex conjunctive representations to the solution of visual discrimination problems with a high degree of "feature ambiguity". These proposals constitute a new view of perirhinal cortex function, one that does not assume strict modularity of function in the occipito-temporal visual stream, but replaces this idea with the notion of a hierarchical representational continuum.

Hippocampus: cognitive processes and neural representations that underlie declarative memory.

The hippocampus serves a critical role in declarative memory--our capacity to recall everyday facts and events. Recent studies using functional brain imaging in humans and neuropsychological analyses of humans and animals with hippocampal damage have revealed some of the elemental cognitive processes mediated by the hippocampus. In addition, recent characterizations of neuronal firing patterns in behaving animals and humans have suggested how neural representations in the hippocampus underlie those elemental cognitive processes in the service of declarative memory.

Uniform Range of Conduction Times From the Lateral Amygdala to Distributed Perirhinal Sites

Much data indicate that the perirhinal (PRH) cortex plays a critical role in declarative memory and that the amygdala facilitates this process under emotionally arousing conditions. However, assuming that the amygdala does so by promoting Hebbian interactions in the PRH cortex is hard to reconcile with the fact that variable distances separate amygdala neurons from their PRH projection sites. Indeed, to achieve a synchronized activation of distributed PRH sites, amygdala axons should display a uniform range of conduction times, irrespective of distance to target. To determine if amygdala axons meet this condition, we measured the antidromic response latencies of lateral amygdala (LA) neurons to electrical stimuli delivered at various rostrocaudal levels of the PRH cortex in cats anesthetized with isoflurane. Although large variations in antidromic response latencies were observed, they were unrelated to the distance between the PRH stimulation sites and LA neurons. To determine whether this result was an artifact due to current spread, two control experiments were performed. First, we examined the antidromic response latency of intrinsic PRH neurons. Although we used the same methods as in the first experiment, the antidromic response latency of PRH neurons to electrical stimuli applied in the PRH cortex increased linearly with the distance between the stimulating and recording sites. Second, we measured the antidromic response latency of PRH neurons projecting to the LA. In this pathway, we also found a statistically significant correlation between conduction times and distance to target. Thus these results support the intriguing possibility that the conduction velocity and/or trajectory of LA axons are adjusted to compensate for variations in distance between the LA and distinct rostrocaudal PRH sites. We hypothesize that because of their uniform range of conduction times to the PRH cortex, LA neurons can generate short time windows of depolarization facilitating Hebbian associations between coincident, but spatially distributed, activity patterns in the PRH cortex. In this context, the temporal scatter of conduction times in the LA to PRH pathway is conceived as a mechanism used to lengthen the period of depolarization to compensate for conduction delays within intrinsic PRH pathways. In part, this mechanism might explain how the amygdala promotes memory storage in emotionally arousing conditions.

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