Recalling Lashley and reconsolidating Hebb.

Many of the foundational theoretical ideas in the field of learning and memory are traced to Donald Hebb. Examination of these ideas and their evolution suggest that Karl Lashley might have significantly influenced their development. Here, we discuss the relationship between Hebb and Lashley, and the parallels between them. Many now investigating the neurobiological basis of memory may be unaware both of Hebb's original descriptions, and the likely substantial contributions of Lashley. Many of their concerns remain with us today, and by clarifying the history we hope to strengthen the foundations of our field.

ERP correlates of object recognition memory in Down syndrome: Do active and passive tasks measure the same thing?

Event related potentials (ERPs) can help to determine the cognitive and neural processes underlying memory functions and are often used to study populations with severe memory impairment. In healthy adults, memory is typically assessed with active tasks, while in patient studies passive memory paradigms are generally used. In this study we examined whether active and passive continuous object recognition tasks measure the same underlying memory process in typically developing (TD) adults and in individuals with Down syndrome (DS), a population with known hippocampal impairment. We further explored how ERPs in these tasks relate to behavioral measures of memory. Data-driven analysis techniques revealed large differences in old-new effects in the active versus passive task in TD adults, but no difference between these tasks in DS. The group with DS required additional processing in the active task in comparison to the TD group in two ways. First, the old-new effect started 150 ms later. Second, more repetitions were required to show the old-new effect. In the group with DS, performance on a behavioral measure of object-location memory was related to ERP measures across both tasks. In total, our results suggest that active and passive ERP memory measures do not differ in DS and likely reflect the use of implicit memory, but not explicit processing, on both tasks. Our findings highlight the need for a greater understanding of the comparison between active and passive ERP paradigms before they are inferred to measure similar functions across populations (e.g., infants or intellectual disability).

Memory formation, consolidation and transformation.

Memory formation is a highly dynamic process. In this review we discuss traditional views of memory and offer some ideas about the nature of memory formation and transformation. We argue that memory traces are transformed over time in a number of ways, but that understanding these transformations requires careful analysis of the various representations and linkages that result from an experience. These transformations can involve: (1) the selective strengthening of only some, but not all, traces as a function of synaptic rescaling, or some other process that can result in selective survival of some traces; (2) the integration (or assimilation) of new information into existing knowledge stores; (3) the establishment of new linkages within existing knowledge stores; and (4) the up-dating of an existing episodic memory. We relate these ideas to our own work on reconsolidation to provide some grounding to our speculations that we hope will spark some new thinking in an area that is in need of transformation.

Parental report of sleep problems in Down syndrome.

BACKGROUND: Children with Down syndrome (DS) suffer from sleep problems, including sleep maintenance problems, as well as snoring, and other symptoms of disordered breathing. To examine sleep in DS, we gave parents a questionnaire assessing their child's sleep. MATERIALS AND METHODS: The parents of 35 children with DS (mean age = 12.65 years, range = 7-18 years) completed the 33-item Children's Sleep Habits Questionnaire. RESULTS: Eighty-five per cent of our sample had sleep disturbance scores in the clinical range (mean = 48.63, SD = 7.15, range = 34-64). Our sample also had significantly elevated scores on the Bedtime Resistance, Sleep Anxiety, Night Wakings, Parasomnias, Sleep Disordered Breathing and Daytime Sleepiness subscales. CONCLUSIONS: Children with DS are at risk for developing symptoms of sleep disordered breathing, and may have additional sleep problems that are unrelated to sleep disordered breathing.

Neuropsychological effects of second language exposure in Down syndrome.

BACKGROUND: While it has been common practice to discourage second language learning in neurodevelopmental disorders involving language impairment, little is known about the effects of second language exposure (SLE) on broader cognitive function in these children. Past studies have not found differences on language tasks in children with Down syndrome (DS) and SLE. We expand on this work to determine the effects on the broader cognitive profile, including tests tapping deficits on neuropsychological measures of prefrontal and hippocampal function. METHOD: This study examined the specific cognitive effects of SLE in children with DS (aged 7-18 years). Children with SLE (n = 13: SLE predominantly Spanish) and children from monolingual homes (n = 28) were assessed on a standardised battery of neuropsychological tests developed for DS, the Arizona Cognitive Test Battery. The current exposure level to a language other than English in the SLE group was greater than 4 h per day on average. RESULTS: No group differences were observed for any outcome, and level of exposure was also not linearly related to neuropsychological outcomes, several of which have been shown to be impaired in past work. CONCLUSION: There were no measurable effects of SLE on neuropsychological function in this sample of children with DS. Potential clinical implications of these findings are discussed.

Down's syndrome: a genetic disorder in biobehavioral perspective.

Down's syndrome is a genetic disorder that can lead to mental retardation of varying degrees. How this chromosomal abnormality causes mental retardation remains an open question. This paper reviews what is currently known about the neural and cognitive features of Down's syndrome, noting the growing evidence of disproportionate impairment of specific systems such as the hippocampal formation, the prefrontal cortex and the cerebellum. The development of animal models of these defects offers a way of ultimately connecting the genetic disorder to its cognitive consequences.

Rat spatial memory tasks adapted for humans: characterization in subjects with intact brain and subjects with selective medial temporal lobe thermal lesions.

In the present paper we describe five tests, 3 of which were designed to be similar to tasks used with rodents. Results obtained from control subjects, patients with selective thermo-coagulation lesions to the medial temporal lobe and results from non-human primates and rodents are discussed. The tests involve memory for spatial locations acquired by moving around in a room, memory for objects subjects interacted with, or memory for objects and their locations. Two of the spatial memory tasks were designed specifically as analogs of the Morris water task and the 8-arm radial-maze tasks used with rats. The Morris water task was modeled by hiding a sensor under the carpet of a room (Invisible Sensor Task). Subjects had to learn its location by using an array of visual cues available in the room. A path integration task was developed in order to study the non-visual acquisition of a cognitive representation of the spatial location of objects. In the non-visual spatial memory task, we blindfolded subjects and led them to a room where they had to find 3 objects and remember their locations. We designed an object location task by placing 4 objects in a room that subjects observed for later recall of their locations. A recognition task, and a novelty detection task were given subsequent to the recall task. An 8-arm radial-maze was recreated by placing stands at equal distance from each other around the room, and asking subjects to visit each stand once, from a central point. A non-spatial working memory task was designed to be the non-spatial equivalent of the radial maze. Search paths recorded on the first trial of the Invisible Sensor Task, when subjects search for the target by trial and error are reported. An analysis of the search paths revealed that patients with lesions to the right or left hippocampus or parahippocampal cortex employed the same type of search strategies as normal controls did, showing similarities and differences to the search behavior recorded in rats. Interestingly, patients with lesions that included the right parahippocampal cortex were impaired relative to patients with lesions to the right hippocampus that spared the parahippocampal cortex, when recall of the sensor was tested after a 30 min delay (Bohbot et al. 1998). No differences were obtained between control subjects and patients with selective thermal lesions to the medial temporal lobe, when tested on the radial-maze, the non-spatial analogue to the radial-maze and the path integration tasks. Differences in methodological procedures, learning strategies and lesion location could account for some of the discrepant results between humans and non-human species. Patients with lesions to the right hippocampus, irrespective of whether the right parahippocampal cortex was spared or damaged, had difficulties remembering the particular configuration and identity of objects in the novelty detection of the object location task. This supports the role of the human right hippocampus for spatial memory, in this case, involving memory for the location of elements in the room; learning known to require the hippocampus in the rat.

The hippocampal complex and long-term memory revisited.

A recent report by Cipolotti et al. demontrates that the hippocampus and perhaps the parahippocampal area are essential for retrieval of remote episodic memory and important for remote semantic memory. This report, along with other recent findings, re-opens the debate about the role of these medial temporal lobe structures, indicating that their role extends much further than traditional theory had suggested.

Place learning in virtual space. III: Investigation of spatial navigation training procedures and their application to fMRI and clinical neuropsychology.

This paper describes the utilization of a desktop virtual environment task, the Computer-Generated (C-G) Arena, in the study of human spatial navigation. First, four experiments examined the efficacy of various training procedures in the C-G Arena. In Experiment 1, participants efficiently located a hidden target after only observing the virtual environment from a fixed position (placement learning). In Experiment 2, participants efficiently located a hidden target after only observing an experimenter search the virtual environment (observational learning). In Experiment 3, participants failed to display a latent learning effect in the virtual environment. In Experiment 4, all training procedures effectively taught participants the layout of the virtual environment, but the observational learning procedure most effectively taught participants the location of a hidden target within the environment. Finally, two experiments demonstrated the application of C-G Arena procedures to neuroimaging (Experiment 5) and neuropsychological (Experiment 6) investigations of human spatial navigation.

Consolidation of memory.

Animal studies have proven useful in addressing aspects of memory formation and consolidation that cannot be readily answered in research with humans. In particular, they offer the possibility of controlling both the extent and locus of brain lesions, and the exact nature of the experiences to be remembered. Taking advantage of these possibilities, recent studies indicated that the graded retrograde amnesia often seen after lesions to the hippocampal system is not uniform across lesion site and task, nor is it an indication that all of the remembered information available in intact subjects becomes available after hippocampal system lesions made a long time after learning. Rather, these studies support the notion that information is stored in both hippocampal and extrahipocampal sites, and that retrieval from different sites involves access to different kinds of information. The strongest evidence in support of this view is the set of findings indicating that when remote memories are retrieved, in either human or animal subjects that have suffered hippocampal system damage, these memories are not qualitatively the same as remote memories retrieved in intact subjects. In sum, memory appears to be rather more dynamic than most current conceptions allow, such that retrieval events trigger new encodings, and these new encodings engage the hippocampal system once again. As a result, older, reactivated memories become more resistant to disruption, and this mechanism helps to explain why graded retrograde amnesia is sometimes seen after brain damage. The use of new neuroimaging techniques, coupled with more sensitive neuropsychological tests in lesioned subjects, should further illuminate the complex nature of memory in coming years. It is likely that animal studies will continue to prove important in these developments.

Hippocampal complex and retrieval of recent and very remote autobiographical memories: evidence from functional magnetic resonance imaging in neurologically intact people.

It has been argued that the role of the hippocampus in memory is time-limited: during a period of memory consolidation, other brain regions such as the neocortex are said to acquire the ability to support memory retention and retrieval on their own. An alternative view is that retention and retrieval of memory for autobiographical episodes depend on the hippocampal complex, regardless of the age of the memory. We examined the participation of the hippocampal complex in a functional magnetic resonance imaging (fMRI) study in which participants were asked to recollect autobiographical events that occurred either within the last 4 years or more than 20 years ago. We found equivalent levels of hippocampal activation in both conditions in all participants (N = 10). In addition, activation in neocortical regions did not differ as a function of the age of the memory, even though most of the recent memories recalled were less than 2 years old and the remote memories more than 35 years old. The results support the notion that the hippocampal complex participates in retention and recovery of even very old autobiographical memories, and place boundary conditions on theories of memory consolidation.

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.

The brain decade in debate: I. Neurobiology of learning and memory.

This article is a transcription of an electronic symposium in which some active researchers were invited by the Brazilian Society for Neuroscience and Behavior (SBNeC) to discuss the last decade's advances in neurobiology of learning and memory. The way different parts of the brain are recruited during the storage of different kinds of memory (e.g., short-term vs long-term memory, declarative vs procedural memory) and even the property of these divisions were discussed. It was pointed out that the brain does not really store memories, but stores traces of information that are later used to create memories, not always expressing a completely veridical picture of the past experienced reality. To perform this process different parts of the brain act as important nodes of the neural network that encode, store and retrieve the information that will be used to create memories. Some of the brain regions are recognizably active during the activation of short-term working memory (e.g., prefrontal cortex), or the storage of information retrieved as long-term explicit memories (e.g., hippocampus and related cortical areas) or the modulation of the storage of memories related to emotional events (e.g., amygdala). This does not mean that there is a separate neural structure completely supporting the storage of each kind of memory but means that these memories critically depend on the functioning of these neural structures. The current view is that there is no sense in talking about hippocampus-based or amygdala-based memory since this implies that there is a one-to-one correspondence. The present question to be solved is how systems interact in memory. The pertinence of attributing a critical role to cellular processes like synaptic tagging and protein kinase A activation to explain the memory storage processes at the cellular level was also discussed.

Multiple trace theory of human memory: computational, neuroimaging, and neuropsychological results.

Hippocampal-neocortical interactions in memory have typically been characterized within the "standard model" of memory consolidation. In this view, memory storage initially requires hippocampal linking of dispersed neocortical storage sites, but over time this need dissipates, and the hippocampal component is rendered unnecessary. This change in function over time is held to account for the retrograde amnesia (RA) gradients often seen in patients with hippocampal damage. Recent evidence, however, calls this standard model into question, and we have recently proposed a new approach, the "multiple memory trace" (MMT) theory. In this view, hippocampal ensembles are always involved in storage and retrieval of episodic information, but semantic (gist) information can be established in neocortex, and will survive damage to the hippocampal system if enough time has elapsed. This approach accounts more readily for the very long RA gradients often observed in amnesia. We report the results of analytic and connectionist simulations that demonstrate the feasibility of MMT. We also report a neuroimaging study showing that retrieval of very remote (25-year-old) memories elicits as much activation in hippocampus as retrieval of quite recent memories. Finally, we report new data from the study of patients with temporal lobe damage, using more sensitive measures than previously the case, showing that deficits in both episodic and spatial detail can be observed even for very remote memories. Overall, these findings indicate that the standard model of memory consolidation, which views the hippocampus as having only a temporary role in memory, is wrong. Instead, the data support the view that for episodic and spatial detail the hippocampal system is always necessary.

The brain decade in debate: I. Neurobiology of learning and memory

This article is a transcription of an electronic symposium in which some active researchers were invited by the Brazilian Society for Neuroscience and Behavior (SBNeC) to discuss the last decade's advances in neurobiology of learning and memory. The way different parts of the brain are recruited during the storage of different kinds of memory (e.g., short-term vs long-term memory, declarative vs procedural memory) and even the property of these divisions were discussed. It was pointed out that the brain does not really store memories, but stores traces of information that are later used to create memories, not always expressing a completely veridical picture of the past experienced reality. To perform this process different parts of the brain act as important nodes of the neural network that encode, store and retrieve the information that will be used to create memories. Some of the brain regions are recognizably active during the activation of short-term working memory (e.g., prefrontal cortex), or the storage of information retrieved as long-term explicit memories (e.g., hippocampus and related cortical areas) or the modulation of the storage of memories related to emotional events (e.g., amygdala). This does not mean that there is a separate neural structure completely supporting the storage of each kind of memory but means that these memories critically depend on the functioning of these neural structures. The current view is that there is no sense in talking about hippocampus-based or amygdala-based memory since this implies that there is a one-to-one correspondence. The present question to be solved is how systems interact in memory. The pertinence of attributing a critical role to cellular processes like synaptic tagging and protein kinase A activation to explain the memory storage processes at the cellular level was also discussed

Memory deficits characterized by patterns of lesions to the hippocampus and parahippocampal cortex.

Spatial and nonspatial memory tests were given to patients with small thermal lesions administered to the medial temporal lobes in an attempt at alleviating pharmacologically resistant epilepsy. In all three spatial memory experiments presented in this paper, patients with lesions that included the right parahippocampal cortex were seriously impaired. Their impairment, together with the performance of patients with lesions to the right hippocampus (sparing the right parahippocampal cortex), provides the different patterns of deficits that lead to different interpretations of the function of the parahippocampal cortex. The distinction between the effects of functional damage in hippocampus and the effects of a lesion to the hippocampus or to regions surrounding the hippocampus, such as the parahippocampal cortex, is emphasized. We conclude that the right parahippocampal cortex participates in spatial memory beyond serving as a gateway to the hippocampus.