On the comparison of a novel serious game and electroencephalography biomarkers for early dementia screening

Patients with amnestic mild cognitive impairment are at high risk for developing Alzheimer's disease. Besides episodic memory dysfunction they show deficits in accessing contextual knowledge that further specifies a general spatial navigation task or an executive function (EF) virtual action planning. Virtual reality (VR) environments have already been successfully used in cognitive rehabilitation and show increased potential for use in neuropsychological evaluation allowing for greater ecological validity while being more engaging and user friendly. In our study we employed the in-house platform of virtual action planning museum (VAP-M) and a sample of 25 MCI and 25 controls, in order to investigate deficits in spatial navigation, prospective memory, and executive function. In addition, we used the morphology of late components in event-related potential (ERP) responses, as a marker for cognitive dysfunction. The related measurements were fed to a common classification scheme facilitating the direct comparison of both approaches. Our results indicate that both the VAP-M and ERP averages were able to differentiate between healthy elders and patients with amnestic mild cognitive impairment and agree with the findings of the virtual action planning supermarket (VAP-S). The sensitivity (specificity) was 100% (98%) for the VAP-M data and 87% (90%) for the ERP responses. Considering that ERPs have proven to advance the early detection and diagnosis of "presymptomatic AD," the suggested VAP-M platform appears as an appealing alternative.

Hippocampus Is Place of Interaction between Unconscious and Conscious Memories.

Recent evidence suggests that humans can form and later retrieve new semantic relations unconsciously by way of hippocampus-the key structure also recruited for conscious relational (episodic) memory. If the hippocampus subserves both conscious and unconscious relational encoding/retrieval, one would expect the hippocampus to be place of unconscious-conscious interactions during memory retrieval. We tested this hypothesis in an fMRI experiment probing the interaction between the unconscious and conscious retrieval of face-associated information. For the establishment of unconscious relational memories, we presented subliminal (masked) combinations of unfamiliar faces and written occupations ("actor" or "politician"). At test, we presented the former subliminal faces, but now supraliminally, as cues for the reactivation of the unconsciously associated occupations. We hypothesized that unconscious reactivation of the associated occupation-actor or politician-would facilitate or inhibit the subsequent conscious retrieval of a celebrity's occupation, which was also actor or politician. Depending on whether the reactivated unconscious occupation was congruent or incongruent to the celebrity's occupation, we expected either quicker or delayed conscious retrieval process. Conscious retrieval was quicker in the congruent relative to a neutral baseline condition but not delayed in the incongruent condition. fMRI data collected during subliminal face-occupation encoding confirmed previous evidence that the hippocampus was interacting with neocortical storage sites of semantic knowledge to support relational encoding. fMRI data collected at test revealed that the facilitated conscious retrieval was paralleled by deactivations in the hippocampus and neocortical storage sites of semantic knowledge. We assume that the unconscious reactivation has pre-activated overlapping relational representations in the hippocampus reducing the neural effort for conscious retrieval. This finding supports the notion of synergistic interactions between conscious and unconscious relational memories in a common, cohesive hippocampal-neocortical memory space.

Acute and Chronic Altitude-Induced Cognitive Dysfunction in Children and Adolescents.

OBJECTIVE To assess whether exposure to high altitude induces cognitive dysfunction in young healthy European children and adolescents during acute, short-term exposure to an altitude of 3450 m and in an age-matched European population permanently living at this altitude. STUDY DESIGN We tested executive function (inhibition, shifting, and working memory), memory (verbal, short-term visuospatial, and verbal episodic memory), and speed processing ability in: (1) 48 healthy nonacclimatized European children and adolescents, 24 hours after arrival at high altitude and 3 months after return to low altitude; (2) 21 matched European subjects permanently living at high altitude; and (3) a matched control group tested twice at low altitude. RESULTS Short-term hypoxia significantly impaired all but 2 (visuospatial memory and processing speed) of the neuropsychological abilities that were tested. These impairments were even more severe in the children permanently living at high altitude. Three months after return to low altitude, the neuropsychological performances significantly improved and were comparable with those observed in the control group tested only at low altitude. CONCLUSIONS Acute short-term exposure to an altitude at which major tourist destinations are located induces marked executive and memory deficits in healthy children. These deficits are equally marked or more severe in children permanently living at high altitude and are expected to impair their learning abilities.

Análisis de conceptos básicos de memoria y aprendizaje : ¿Hasta qué punto los "dogmas" cognitivos son realmente "dogmas"?

El aprendizaje como proceso se puede considerar un avance evolutivo importante para todos los sistemas vivientes que lo adquirieron en las tempranas épocas del desarrollo de la vida. La percepción de un entorno que tiene “pasado" y “presente" permitió a los animales primitivos adquirir una visión más completa del mundo que los rodeaba. El uso cognitivo de la información que está disponible en un sistema viviente se le reconoce ahora como “aprendizaje". A pesar que han pasado muchos años y muchos investigadores han estado muy comprometidos en el estudio de la memoria y el aprendizaje, su intrincada naturaleza todavía no se comprende bien. En este trabajo se amplían muchos términos comunes en la investigación de este tema, como memoria, aprendizaje y ensayo redefiniéndose en un contexto más acotado con la intención de uniformar su comprensión. Se vuelve a discutir el modelo de aprendizaje en términos de un “circuito de aprendizaje". También se amplía el concepto unificador de “engrama de la unidad vectorial de la memoria" para el proceso de aprendizaje y el almacenamiento de la información, descrito con anterioridad. Finalmente, las implicaciones del modelo propuesto se consideran en el contexto de patologías que producen déficit de memoria, evaluándose las predicciones del modelo con la evidencia comportamental de pacientes con lesiones localizadas en ciertas partes del cerebro.

Changes in the Papez Circuit in early stages of Alzheimer's Disease

Alzheimer's disease (AD) is the most common cause of demenMa. Neuronal and synapMc losses occur iniMally and predominantly in the medial temporal lobe structures including hippocampus, amygdala and thalamus, structures that belong to the Papez circuit. The integrity of the connecMons amongst them is essenMal for episodic memory, which is specifically impaired in AD. For this reason we have invesMgated the degeneraMon paRern of subcorMcal structures and its relaMon to early stages of AD, i.e. Mild CogniMve Impairment (MCI), both in the amnesic and mulMdomain types using structural magneMc resonance imaging (using a 3T GE scanner) and VBM‐DARTEL.

Segregating the functions of human hippocampus

It is now accepted that hippocampal lesions impair episodic memory. However, the precise functional role of the hippocampus in episodic memory remains elusive. Recent functional imaging data implicate the hippocampus in processing novelty, a finding supported by human in vivo recordings and event-related potential studies. Here we measure hippocampal responses to novelty, using functional MRI (fMRI), during an item-learning paradigm generated from an artificial grammar system. During learning, two distinct types of novelty were periodically introduced: perceptual novelty, pertaining to the physical characteristics of stimuli (in this case visual characteristics), and exemplar novelty, reflecting semantic characteristics of stimuli (in this case grammatical status within a rule system). We demonstrate a left anterior hippocampal response to both types of novelty and adaptation of these responses with stimulus familiarity. By contrast to these novelty effects, we also show bilateral posterior hippocampal responses with increasing exemplar familiarity. These results suggest a functional dissociation within the hippocampus with respect to the relative familiarity of study items. Neural responses in anterior hippocampus index generic novelty, whereas posterior hippocampal responses index familiarity to stimuli that have behavioral relevance (i.e., only exemplar familiarity). These findings add to recent evidence for functional segregation within the human hippocampus during learning.

Brain activity evidence for recognition without recollection after early hippocampal damage

Amnesic patients with early and seemingly isolated hippocampal injury show relatively normal recognition memory scores. The cognitive profile of these patients raises the possibility that this recognition performance is maintained mainly by stimulus familiarity in the absence of recollection of contextual information. Here we report electrophysiological data on the status of recognition memory in one of the patients, Jon. Jon's recognition of studied words lacks the event-related potential (ERP) index of recollection, viz., an increase in the late positive component (500–700 ms), under conditions that elicit it reliably in normal subjects. On the other hand, a decrease of the ERP amplitude between 300 and 500 ms, also reliably found in normal subjects, is well preserved. This so-called N400 effect has been linked to stimulus familiarity in previous ERP studies of recognition memory. In Jon, this link is supported by the finding that his recognized and unrecognized studied words evoked topographically distinct ERP effects in the N400 time window. These data suggest that recollection is more dependent on the hippocampal formation than is familiarity, consistent with the view that the hippocampal formation plays a special role in episodic memory, for which recollection is so critical.

General and specific brain regions involved in encoding and retrieval of events: what, where, and when.

Remembering an event involves not only what happened, but also where and when it occurred. We measured regional cerebral blood flow by positron emission tomography during initial encoding and subsequent retrieval of item, location, and time information. Multivariate image analysis showed that left frontal brain regions were always activated during encoding, and right superior frontal regions were always activated at retrieval. Pairwise image subtraction analyses revealed information-specific activations at (i) encoding, item information in left hippocampal, location information in right parietal, and time information in left fusiform regions; and (ii) retrieval, item in right inferior frontal and temporal, location in left frontal, and time in anterior cingulate cortices. These results point to the existence of general encoding and retrieval networks of episodic memory whose operations are augmented by unique brain areas recruited for processing specific aspects of remembered events.

The effects of different review opportunities on schematisation of knowledge

Recent research suggests that early in learning, students primarily use episodic memory when recalling information, but as learning develops and schematisation occurs, students' knowledge is likely to be dominated by semantic memory. This shift has been examined through student's memory awareness; 'remembering' is linked to episodic memory and 'knowing' is linked to semantic memory. This paper explores the effect of different review opportunities on students' memory awareness and schematisation, and reports on findings that indicate students are more likely to shift from 'remembering' to 'knowing' if they have the opportunity to review the learning material, but regularly and in different formats. (C) 2002 Elsevier Science Ltd. All rights reserved.

Recalling yesterday and predicting tomorrow

Three-, 4- and 5-year-old children were asked to report something that they did do yesterday and something that they were going to do tomorrow. They were also asked to recall events that had not occurred yesterday, and predict events that would not occur tomorrow. In two studies these simple questions revealed striking age differences in the ability to report personal events from the past and the future. Only a minority of 3-year-olds but a majority of the older children were able to appropriately answer these questions. These findings substantiate the proposal that the ability to recall past events and the ability to predict future events (i.e., mental time travel), emerge in tandem between the ages of 3 and 5 years. (c) 2005 Elsevier Inc. All rights reserved.

Making decisions with the future in mind: Developmental and comparative identification of mental time travel

Mechanisms that produce behavior which increase future survival chances provide an adaptive advantage. The flexibility of human behavior is at least partly the result of one such mechanism, our ability to travel mentally in time and entertain potential future scenarios. We can study mental time travel in children using language. Current results suggest that key developments occur between the ages of three to five. However, linguistic performance can be misleading as language itself is developing. We therefore advocate the use of methodologies that focus on future-oriented action. Mental time travel required profound changes in humans' motivational system, so that current behavior could be directed to secure not just present, but individually anticipated future needs. Such behavior should be distinguishable from behavior based on current drives, or on other mechanisms. We propose an experimental paradigm that provides subjects with an opportunity to act now to satisfy a need not currently experienced. This approach may be used to assess mental time travel in nonhuman animals. We conclude by describing a preliminary study employing an adaptation of this paradigm for children. (c) 2005 Elsevier Inc. All rights reserved.

Cognitive neuroimaging: Cognitive science out of the armchair

Cognitive scientists were not quick to embrace the functional neuroimaging technologies that emerged during the late 20th century. In this new century, cognitive scientists continue to question, not unreasonably, the relevance of functional neuroimaging investigations that fail to address questions of interest to cognitive science. However, some ultra-cognitive scientists assert that these experiments can never be of relevance to the Study of cognition. Their reasoning reflects an adherence to a functionalist philosophy that arbitrarily and purposefully distinguishes mental information-processing systems from brain or brain-like operations. This article addresses whether data from properly conducted functional neuroimaging studies can inform and Subsequently constrain the assumptions of theoretical cognitive models. The article commences with a focus upon the functionalist philosophy espoused by the ultra-cognitive scientists, contrasting it with the materialist philosophy that motivates both cognitive neuromiaging investigations and connectionist modelling of cognitive systems. Connectionism and cognitive neuroimaging share many features, including an emphasis on unified cognitive and neural models of systems that combine localist and distributed representations. The utility of designing cognitive neuroimaging studies to test (primarily) connectionist models of cognitive phenomena is illustrated using data from functional magnetic resonance imaging (fMRI) investigations of language production and episodic memory. (C) 2005 Elsevier Inc. All rights reserved.

Event related potential (ERP) evidence for selective impairment of verbal recollection in abstinent recreational methylenedioxymethamphetamine (“Ecstasy”)/polydrug users

Objectives Ecstasy is a recreational drug whose active ingredient, 3,4-methylenedioxymethamphetamine (MDMA), acts predominantly on the serotonergic system. Although MDMA is known to be neurotoxic in animals, the long-term effects of recreational Ecstasy use in humans remain controversial but one commonly reported consequence is mild cognitive impairment particularly affecting verbal episodic memory. Although event-related potentials (ERPs) have made significant contributions to our understanding of human memory processes, until now they have not been applied to study the long-term effects of Ecstasy. The aim of this study was to examine the effects of past Ecstasy use on recognition memory for both verbal and non-verbal stimuli using ERPs. Methods We compared the ERPs of 15 Ecstasy/polydrug users with those of 14 cannabis users and 13 non-illicit drug users as controls. Results Despite equivalent memory performance, Ecstasy/polydrug users showed an attenuated late positivity over left parietal scalp sites, a component associated with the specific memory process of recollection. Conlusions This effect was only found in the word recognition task which is consistent with evidence that left hemisphere cognitive functions are disproportionately affected by Ecstasy, probably because the serotonergic system is laterally asymmetrical. Experimentally, decreasing central serotonergic activity through acute tryptophan depletion also selectively impairs recollection, and this too suggests the importance of the serotonergic system. Overall, our results suggest that Ecstasy users, who also use a wide range of other drugs, show a durable abnormality in a specific ERP component thought to be associated with recollection.

The impact of the CACNA1C gene polymorphism on frontolimbic function in bipolar disorder

Genome-wide association studies in bipolar disorder (BD)1 have implicated a single-nucleotide polymorphism (rs1006737, G right arrow A) in the CACNA1C gene, which encodes for the alpha 1c (CAV1.2) subunit of the voltage-gated, L-type calcium channel. Neuroimaging studies of healthy individuals report that this risk allele modulates brain function within limbic (amygdala, anterior cingulate gyrus) and hippocampal regions during tasks of reward processing2, 3 and episodic memory. Moreover, animal studies suggest that the CaV1.2 L-type calcium channels influence emotional behaviour through enhanced neurotransmission via the lateral amygdala pathway. On the basis of this evidence, we tested the hypotheses that the CACNA1C rs1006737 risk allele will modulate neural responses within predefined prefrontal and subcortical regions of interest during emotional face processing and that this effect would be amplified in BD patients.

Conversational interaction in the scanner:mentalizing during language processing as revealed by MEG

Humans are especially good at taking another's perspective-representing what others might be thinking or experiencing. This "mentalizing" capacity is apparent in everyday human interactions and conversations. We investigated its neural basis using magnetoencephalography. We focused on whether mentalizing was engaged spontaneously and routinely to understand an utterance's meaning or largely on-demand, to restore "common ground" when expectations were violated. Participants conversed with 1 of 2 confederate speakers and established tacit agreements about objects' names. In a subsequent "test" phase, some of these agreements were violated by either the same or a different speaker. Our analysis of the neural processing of test phase utterances revealed recruitment of neural circuits associated with language (temporal cortex), episodic memory (e.g., medial temporal lobe), and mentalizing (temporo-parietal junction and ventromedial prefrontal cortex). Theta oscillations (3-7 Hz) were modulated most prominently, and we observed phase coupling between functionally distinct neural circuits. The episodic memory and language circuits were recruited in anticipation of upcoming referring expressions, suggesting that context-sensitive predictions were spontaneously generated. In contrast, the mentalizing areas were recruited on-demand, as a means for detecting and resolving perceived pragmatic anomalies, with little evidence they were activated to make partner-specific predictions about upcoming linguistic utterances.