Role of kinin B1 and B2 receptors in memory consolidation during the aging process of mice

Under physiological conditions, elderly people present memory deficit associated with neuronal loss. This pattern is also associated with Alzheimer`s disease but, in this case, in a dramatically intensified level. Kinin receptors have been involved in neurodegeneration and increase of amyloid-beta concentration, associated with Alzheimer`s disease (AD). Considering these findings, this work evaluated the role of kinin receptors in memory consolidation during the aging process. Male C57BI/6 (wt), knock-out B1 (koB1) or B2 (koB2) mice (3, 6, 12 and 18-month-old - mo; n = 10 per group) were submitted to an acquisition session, reinforcement to learning (24 h later: test 1) and final test (7 days later: test 2), in an active avoidance apparatus, to evaluate memory. Conditioned avoidance responses (CAR, % of 50 trials) were registered. In acquisition sessions, similar CAR were obtained among age matched animals from all strains. However, a significant decrease in CAR was observed throughout the aging process (3mo: 8.8 +/- 2.3%; 6mo: 4.1 +/- 0.6%; 12mo: 2.2 +/- 0.6%, 18mo: 3.6 +/- 0.6%, P < 0.01), indicating a reduction in the learning process. In test 1, as expected, memory retention increased significantly (P < 0.05) in all 3- and 6-month-old animals as well as in 12-month-old-wt and 12-month-old-koB1 (P < 0.01), compared to the training session. However, 12-month-old-koB2 and all 18-month-old animals did not show an increase in memory retention. In test 2, 3- and 6-month-old wt and koB1 mice of all ages showed a significant improvement in memory (P < 0.05) compared to test 1. However, 12-month-old wt and koB2 mice of all ages showed no difference in memory retention. We suggest that, during the aging process, the B1 receptor could be involved in neurodegeneration and memory loss. Nevertheless, the B2 receptor is apparently acting as a neuroprotective factor. (C) 2009 Elsevier Ltd. All rights reserved.

Episodic and semantic memory in children with mesial temporal sclerosis

The aim of this study was to analyze semantic and episodic memory deficits in children with mesial temporal sclerosis (MTS) and their correlation with clinical epilepsy variables. For this purpose, 19 consecutive children and adolescents with MTS (8 to 16 years old) were evaluated and their performance on five episodic memory tests (short- and long-term memory and learning) and four semantic memory tests was compared with that of 28 healthy volunteers. Patients performed worse on tests of immediate and delayed verbal episodic memory, visual episodic memory, verbal and visual learning, mental scanning for semantic clues, object naming, word definition, and repetition of sentences. Clinical variables such as early age at seizure onset, severity of epilepsy, and polytherapy impaired distinct types of memory. These data confirm that children with MTS have episodic memory deficits and add new information on semantic memory. The data also demonstrate that clinical variables contribute differently to episodic and semantic memory performance. (C) 2011 Elsevier Inc. All rights reserved.

Special issue on methods and learning in functional MRI: Introductory remarks

This special issue represents a further exploration of some issues raised at a symposium entitled “Functional magnetic resonance imaging: From methods to madness” presented during the 15th annual Theoretical and Experimental Neuropsychology (TENNET XV) meeting in Montreal, Canada in June, 2004. The special issue’s theme is methods and learning in functional magnetic resonance imaging (fMRI), and it comprises 6 articles (3 reviews and 3 empirical studies). The first (Amaro and Barker) provides a beginners guide to fMRI and the BOLD effect (perhaps an alternative title might have been “fMRI for dummies”). While fMRI is now commonplace, there are still researchers who have yet to employ it as an experimental method and need some basic questions answered before they venture into new territory. This article should serve them well. A key issue of interest at the symposium was how fMRI could be used to elucidate cerebral mechanisms responsible for new learning. The next 4 articles address this directly, with the first (Little and Thulborn) an overview of data from fMRI studies of category-learning, and the second from the same laboratory (Little, Shin, Siscol, and Thulborn) an empirical investigation of changes in brain activity occurring across different stages of learning. While a role for medial temporal lobe (MTL) structures in episodic memory encoding has been acknowledged for some time, the different experimental tasks and stimuli employed across neuroimaging studies have not surprisingly produced conflicting data in terms of the precise subregion(s) involved. The next paper (Parsons, Haut, Lemieux, Moran, and Leach) addresses this by examining effects of stimulus modality during verbal memory encoding. Typically, BOLD fMRI studies of learning are conducted over short time scales, however, the fourth paper in this series (Olson, Rao, Moore, Wang, Detre, and Aguirre) describes an empirical investigation of learning occurring over a longer than usual period, achieving this by employing a relatively novel technique called perfusion fMRI. This technique shows considerable promise for future studies. The final article in this special issue (de Zubicaray) represents a departure from the more familiar cognitive neuroscience applications of fMRI, instead describing how neuroimaging studies might be conducted to both inform and constrain information processing models of cognition.

The association between auditory memory span and speech rate in children from kindergarten to sixth grade

This study reexamined the association between speech rate and memory span in children from kindergarten to sixth grade (N = 152) in order to potentially account for the inconsistencies within the published literature on this topic. Some of the inconsistencies in past research may reflect the different methods adopted in assessing speech rate. In particular, repeating word triples may itself involve memory demands, contaminating the correlation between speech rate and memory span in younger children. Analyses using composite speech rate and memory span measures showed that speech rate for word triples shared variance with memory span that was independent of speech rate for single words. Moreover, speech rate for word triples was largely redundant with age in explaining additional variation in memory span once the effects of speech rate for single words were controlled. (C) 2002 Elsevier Science.

Hierarchical Reinforcement Learning in Behavior and the Brain

Dissertation presented to obtain the Ph.D degree in Biology, Neuroscience

Electrical neuroimaging of memory discrimination based on single-trial multisensory learning.

Multisensory experiences influence subsequent memory performance and brain responses. Studies have thus far concentrated on semantically congruent pairings, leaving unresolved the influence of stimulus pairing and memory sub-types. Here, we paired images with unique, meaningless sounds during a continuous recognition task to determine if purely episodic, single-trial multisensory experiences can incidentally impact subsequent visual object discrimination. Psychophysics and electrical neuroimaging analyses of visual evoked potentials (VEPs) compared responses to repeated images either paired or not with a meaningless sound during initial encounters. Recognition accuracy was significantly impaired for images initially presented as multisensory pairs and could not be explained in terms of differential attention or transfer of effects from encoding to retrieval. VEP modulations occurred at 100-130ms and 270-310ms and stemmed from topographic differences indicative of network configuration changes within the brain. Distributed source estimations localized the earlier effect to regions of the right posterior temporal gyrus (STG) and the later effect to regions of the middle temporal gyrus (MTG). Responses in these regions were stronger for images previously encountered as multisensory pairs. Only the later effect correlated with performance such that greater MTG activity in response to repeated visual stimuli was linked with greater performance decrements. The present findings suggest that brain networks involved in this discrimination may critically depend on whether multisensory events facilitate or impair later visual memory performance. More generally, the data support models whereby effects of multisensory interactions persist to incidentally affect subsequent behavior as well as visual processing during its initial stages.

Verbal learning in mild cognitive impairment and alzheimer's disease : behavioural and neural approaches

The main focus of the present thesis was at verbal episodic memory processes that are particularly vulnerable to preclinical and clinical Alzheimer’s disease (AD). Here these processes were studied by a word learning paradigm, cutting across the domains of memory and language learning studies. Moreover, the differentiation between normal aging, mild cognitive impairment (MCI) and AD was studied by the cognitive screening test CERAD. In study I, the aim was to examine how patients with amnestic MCI differ from healthy controls in the different CERAD subtests. Also, the sensitivity and specificity of the CERAD screening test to MCI and AD was examined, as previous studies on the sensitivity and specificity of the CERAD have not included MCI patients. The results indicated that MCI is characterized by an encoding deficit, as shown by the overall worse performance on the CERAD Wordlist learning test compared with controls. As a screening test, CERAD was not very sensitive to MCI. In study II, verbal learning and forgetting in amnestic MCI, AD and healthy elderly controls was investigated with an experimental word learning paradigm, where names of 40 unfamiliar objects (mainly archaic tools) were trained with or without semantic support. The object names were trained during a 4-day long period and a follow-up was conducted one week, 4 weeks and 8 weeks after the training period. Manipulation of semantic support was included in the paradigm because it was hypothesized that semantic support might have some beneficial effects in the present learning task especially for the MCI group, as semantic memory is quite well preserved in MCI in contrast to episodic memory. We found that word learning was significantly impaired in MCI and AD patients, whereas forgetting patterns were similar across groups. Semantic support showed a beneficial effect on object name retrieval in the MCI group 8 weeks after training, indicating that the MCI patients’ preserved semantic memory abilities compensated for their impaired episodic memory. The MCI group performed equally well as the controls in the tasks tapping incidental learning and recognition memory, whereas the AD group showed impairment. Both the MCI and the AD group benefited less from phonological cueing than the controls. Our findings indicate that acquisition is compromised in both MCI and AD, whereas long13 term retention is not affected to the same extent. Incidental learning and recognition memory seem to be well preserved in MCI. In studies III and IV, the neural correlates of naming newly learned objects were examined in healthy elderly subjects and in amnestic MCI patients by means of positron emission tomography (PET) right after the training period. The naming of newly learned objects by healthy elderly subjects recruited a left-lateralized network, including frontotemporal regions and the cerebellum, which was more extensive than the one related to the naming of familiar objects (study III). Semantic support showed no effects on the PET results for the healthy subjects. The observed activation increases may reflect lexicalsemantic and lexical-phonological retrieval, as well as more general associative memory mechanisms. In study IV, compared to the controls, the MCI patients showed increased anterior cingulate activation when naming newly learned objects that had been learned without semantic support. This suggests a recruitment of additional executive and attentional resources in the MCI group.

Novel word learning ability in chronic post-stroke aphasia : variability and modality effects

Novel word learning has been rarely studied in people with aphasia (PWA), although it can provide a relatively pure measure of their learning potential, and thereby contribute to the development of effective aphasia treatment methods. The main aim of the present thesis was to explore the capacity of PWA for associative learning of word–referent pairings and cognitive-linguistic factors related to it. More specifically, the thesis examined learning and long-term maintenance of the learned pairings, the role of lexical-semantic abilities in learning as well as acquisition of phonological versus semantic information in associative novel word learning. Furthermore, the effect of modality on associative novel word learning and the neural underpinnings of successful learning were explored. The learning experiments utilized the Ancient Farming Equipment (AFE) paradigm that employs drawings of unfamiliar referents and their unfamiliar names. Case studies of Finnishand English-speaking people with chronic aphasia (n = 6) were conducted in the investigation. The learning results of PWA were compared to those of healthy control participants, and active production of the novel words and their semantic definitions was used as learning outcome measures. PWA learned novel word–novel referent pairings, but the variation between individuals was very wide, from more modest outcomes (Studies I–II) up to levels on a par with healthy individuals (Studies III–IV). In incidental learning of semantic definitions, none of the PWA reached the performance level of the healthy control participants. Some PWA maintained part of the learning outcomes up to months post-training, and one individual showed full maintenance of the novel words at six months post-training (Study IV). Intact lexical-semantic processing skills promoted learning in PWA (Studies I–II) but poor phonological short-term memory capacities did not rule out novel word learning. In two PWA with successful learning and long-term maintenance of novel word–novel referent pairings, learning relied on orthographic input while auditory input led to significantly inferior learning outcomes (Studies III–IV). In one of these individuals, this previously undetected modalityspecific learning ability was successfully translated into training with familiar but inaccessible everyday words (Study IV). Functional magnetic resonance imaging revealed that this individual had a disconnected dorsal speech processing pathway in the left hemisphere, but a right-hemispheric neural network mediated successful novel word learning via reading. Finally, the results of Study III suggested that the cognitive-linguistic profile may not always predict the optimal learning channel for an individual with aphasia. Small-scale learning probes seem therefore useful in revealing functional learning channels in post-stroke aphasia.

Visual word learning in good and poor readers

Forty students from regular, grade five classes were divided into two groups of twenty, a good reader group and a' poor reader group, on the basis. of their reading scores on Canadian Achievement Tests. .The subjects took. part in four experimental conditions iM which they .learned lists of pronounceable and unprono~nceable pseudowords, some with semantic referents, and responded to questions designed tci test visual perceptu~l learning and lexical ·and semantic association learning. It' was hypothesized "that the good reade~ group would be able to make use of graphemic and phonemic redundancy patterns in order to improv~·visuSl perceptual learning and lexical and semantic association lea~ningto a greater extent. than would .the poor reader gr6up. The data supported this hypothesis, and also indicated that, although the poor readers were less adept at using familiar sound and letter patterns, they were more dependent on· such pa~terns as an aid to visual recognition memory and semantic recall than were the good readers. It wa.s postulated that poor readers are in a double- ~ . bind situatio~ of having to choose between using weak graphemic-semantic associations or gr~pheme-phoneme associations which are also weak and which have hindered them in developing automaticity in. reading.

Learning Commonsense Categorical Knowledge in a Thread Memory System

If we are to understand how we can build machines capable of broad purpose learning and reasoning, we must first aim to build systems that can represent, acquire, and reason about the kinds of commonsense knowledge that we humans have about the world. This endeavor suggests steps such as identifying the kinds of knowledge people commonly have about the world, constructing suitable knowledge representations, and exploring the mechanisms that people use to make judgments about the everyday world. In this work, I contribute to these goals by proposing an architecture for a system that can learn commonsense knowledge about the properties and behavior of objects in the world. The architecture described here augments previous machine learning systems in four ways: (1) it relies on a seven dimensional notion of context, built from information recently given to the system, to learn and reason about objects' properties; (2) it has multiple methods that it can use to reason about objects, so that when one method fails, it can fall back on others; (3) it illustrates the usefulness of reasoning about objects by thinking about their similarity to other, better known objects, and by inferring properties of objects from the categories that they belong to; and (4) it represents an attempt to build an autonomous learner and reasoner, that sets its own goals for learning about the world and deduces new facts by reflecting on its acquired knowledge. This thesis describes this architecture, as well as a first implementation, that can learn from sentences such as ``A blue bird flew to the tree'' and ``The small bird flew to the cage'' that birds can fly. One of the main contributions of this work lies in suggesting a further set of salient ideas about how we can build broader purpose commonsense artificial learners and reasoners.

A Mismatch-Based Model for Memory Reconsolidation and Extinction in Attractor Networks

OSAN, R. , TORT, A. B. L. , AMARAL, O. B. . A mismatch-based model for memory reconsolidation and extinction in attractor networks. Plos One, v. 6, p. e23113, 2011.

The Dorsolateral Periaqueductal Gray and Its Role in Mediating Fear Learning to Life Threatening Events

The dorsolateral column of the periaqueductal gray (dlPAG) integrates aversive emotional experiences and represents an important site responding to life threatening situations, such as hypoxia, cardiac pain and predator threats. Previous studies have shown that the dorsal PAG also supports fear learning; and we have currently explored how the dlPAG influences associative learning. We have first shown that N-methyl-D-aspartate (NMDA) 100 pmol injection in the dlPAG works as a valuable unconditioned stimulus (US) for the acquisition of olfactory fear conditioning (OFC) using amyl acetate odor as conditioned stimulus (CS). Next, we revisited the ascending projections of the dlPAG to the thalamus and hypothalamus to reveal potential paths that could mediate associative learning during OFC. Accordingly, the most important ascending target of the dlPAG is the hypothalamic defensive circuit, and we were able to show that pharmacological inactivation using beta-adrenoceptor blockade of the dorsal premammillary nucleus, the main exit way for the hypothalamic defensive circuit to thalamo-cortical circuits involved in fear learning, impaired the acquisition of the OFC promoted by NMDA stimulation of the dlPAG. Moreover, our tracing study revealed multiple parallel paths from the dlPAG to several thalamic targets linked to cortical-hippocampal-amygdalar circuits involved in fear learning. Overall, the results point to a major role of the dlPAG in the mediation of aversive associative learning via ascending projections to the medial hypothalamic defensive circuit, and perhaps, to other thalamic targets, as well. These results provide interesting perspectives to understand how life threatening events impact on fear learning, and should be useful to understand pathological fear memory encoding in anxiety disorders.

Motor learning, retention and transfer after virtual-reality-based training in Parkinson's disease - effect of motor and cognitive demands of games: a longitudinal, controlled clinical study

Objectives To evaluate the learning, retention and transfer of performance improvements after Nintendo Wii Fit (TM) training in patients with Parkinson's disease and healthy elderly people. Design Longitudinal, controlled clinical study. Participants Sixteen patients with early-stage Parkinson's disease and 11 healthy elderly people. Interventions Warm-up exercises and Wii Fit training that involved training motor (shifts centre of gravity and step alternation) and cognitive skills. A follow-up evaluative Wii Fit session was held 60 days after the end of training. Participants performed a functional reach test before and after training as a measure of learning transfer. Main outcome measures Learning and retention were determined based on the scores of 10 Wii Fit games over eight sessions. Transfer of learning was assessed after training using the functional reach test. Results Patients with Parkinson's disease showed no deficit in learning or retention on seven of the 10 games, despite showing poorer performance on five games compared with the healthy elderly group. Patients with Parkinson's disease showed marked learning deficits on three other games, independent of poorer initial performance. This deficit appears to be associated with cognitive demands of the games which require decision-making, response inhibition, divided attention and working memory. Finally, patients with Parkinson's disease were able to transfer motor ability trained on the games to a similar untrained task. Conclusions The ability of patients with Parkinson's disease to learn, retain and transfer performance improvements after training on the Nintendo Wii Fit depends largely on the demands, particularly cognitive demands, of the games involved, reiterating the importance of game selection for rehabilitation purposes. (C) 2012 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Deep learning for computer vision: a comparison between convolutional neural networks and hierarchical temporal memories on object recognition tasks

In recent years, Deep Learning techniques have shown to perform well on a large variety of problems both in Computer Vision and Natural Language Processing, reaching and often surpassing the state of the art on many tasks. The rise of deep learning is also revolutionizing the entire field of Machine Learning and Pattern Recognition pushing forward the concepts of automatic feature extraction and unsupervised learning in general. However, despite the strong success both in science and business, deep learning has its own limitations. It is often questioned if such techniques are only some kind of brute-force statistical approaches and if they can only work in the context of High Performance Computing with tons of data. Another important question is whether they are really biologically inspired, as claimed in certain cases, and if they can scale well in terms of "intelligence". The dissertation is focused on trying to answer these key questions in the context of Computer Vision and, in particular, Object Recognition, a task that has been heavily revolutionized by recent advances in the field. Practically speaking, these answers are based on an exhaustive comparison between two, very different, deep learning techniques on the aforementioned task: Convolutional Neural Network (CNN) and Hierarchical Temporal memory (HTM). They stand for two different approaches and points of view within the big hat of deep learning and are the best choices to understand and point out strengths and weaknesses of each of them. CNN is considered one of the most classic and powerful supervised methods used today in machine learning and pattern recognition, especially in object recognition. CNNs are well received and accepted by the scientific community and are already deployed in large corporation like Google and Facebook for solving face recognition and image auto-tagging problems. HTM, on the other hand, is known as a new emerging paradigm and a new meanly-unsupervised method, that is more biologically inspired. It tries to gain more insights from the computational neuroscience community in order to incorporate concepts like time, context and attention during the learning process which are typical of the human brain. In the end, the thesis is supposed to prove that in certain cases, with a lower quantity of data, HTM can outperform CNN.

Better Memory and Neural Efficiency in Young Apolipoprotein E 4 Carriers

The apolipoprotein E (APOE) epsilon4 allele is the major genetic risk factor for Alzheimer's disease, but an APOE effect on memory performance and memory-related neurophysiology in young, healthy subjects is unknown. We found an association of APOE epsilon4 with better episodic memory compared with APOE epsilon2 and epsilon3 in 340 young, healthy persons. Neuroimaging was performed in a subset of 34 memory-matched individuals to study genetic effects on memory-related brain activity independently of differential performance. E4 carriers decreased brain activity over 3 learning runs, whereas epsilon2 and epsilon3 carriers increased activity. This smaller neural investment of epsilon4 carriers into learning reappeared during retrieval: epsilon4 carriers exhibited reduced retrieval-related activity with equal retrieval performance. APOE isoforms had no differential effects on cognitive measures other than memory, brain volumes, and brain activity related to working memory. We suggest that APOE epsilon4 is associated with good episodic memory and an economic use of memory-related neural resources in young, healthy humans.