Francisco Aboitiz

Anatomy, Evolutionary Biology, Neuroscience

40.24

Publications

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    Ignacio Negrón-Oyarzo · Francisco Aboitiz · Pablo Fuentealba
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    ABSTRACT: Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.
    Full-text · Article · Jan 2016
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    Patricia Soto-Icaza · Francisco Aboitiz · Pablo Billeke
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    ABSTRACT: Social skills refer to a wide group of abilities that allow us to interact and communicate with others. Children learn how to solve social situations by predicting and understanding other's behaviors. The way in which humans learn to interact successfully with others encompasses a complex interaction between neural, behavioral, and environmental elements. These have a role in the accomplishment of positive developmental outcomes, including peer acceptance, academic achievement, and mental health. All these social abilities depend on widespread brain networks that are recently being studied by neuroscience. In this paper, we will first review the studies on this topic, aiming to clarify the behavioral and neural mechanisms related to the acquisition of social skills during infancy and their appearance in time. Second, we will briefly describe how developmental diseases like Autism Spectrum Disorders (ASD) can inform about the neurobiological mechanisms of social skills. We finally sketch a general framework for the elaboration of cognitive models in order to facilitate the comprehension of human social development.
    Full-text · Article · Oct 2015 · Frontiers in Neuroscience
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    Francisco Aboitiz · Juan F. Montiel
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    ABSTRACT: There are remarkable similarities between the brains of mammals and birds in terms of microcircuit architecture, despite obvious differences in gross morphology and development. While in reptiles and birds the most expanding component (the dorsal ventricular ridge) displays an overall nuclear shape and derives from the lateral and ventral pallium, in mammals a dorsal pallial, six-layered isocortex shows the most remarkable elaboration. Regardless of discussions about possible homologies between mammalian and avian brains, a main question remains in explaining the emergence of the mammalian isocortex, because it represents a unique phenotype across amniotes. In this article, we propose that the origin of the isocortex was driven by behavioral adaptations involving olfactory driven goal-directed and navigating behaviors. These adaptations were linked with increasing sensory development, which provided selective pressure for the expansion of the dorsal pallium. The latter appeared as an interface in olfactory-hippocampal networks, contributing somatosensory information for navigating behavior. Sensory input from other modalities like vision and audition were subsequently recruited into this expanding region, contributing to multimodal associative networks.
    Full-text · Article · Oct 2015 · Frontiers in Neuroscience
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    ABSTRACT: While earlier Brain-Computer Interface (BCI) studies have mostly focused on modulating specific brain regions or signals, new developments in pattern classification of brain states are enabling real-time decoding and modulation of an entire functional network. The present study proposes a new method for real-time pattern classification and neurofeedback of brain states from electroencephalographic (EEG) signals. It involves the creation of a fused classification model based on the method of Common Spatial Patterns (CSPs) from data of several healthy individuals. The subject-independent model is then used to classify EEG data in real-time and provide feedback to new individuals. In a series of offline experiments involving training and testing of the classifier with individual data from 27 healthy subjects, a mean classification accuracy of 75.30% was achieved, demonstrating that the classification system at hand can reliably decode two types of imagery used in our experiments, i.e., happy emotional imagery and motor imagery. In a subsequent experiment it is shown that the classifier can be used to provide neurofeedback to new subjects, and that these subjects learn to " match " their brain pattern to that of the fused classification model in a few days of neurofeedback training. This finding can have important implications for future studies on neurofeedback and its clinical applications on neuropsychiatric disorders.
    Full-text · Article · Oct 2015 · Frontiers in Behavioral Neuroscience
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    Juan F Montiel · Francisco Aboitiz
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    ABSTRACT: Together with a complex variety of behavioral, physiological, morphological, and neurobiological innovations, mammals are characterized by the development of an extensive isocortex (also called neocortex) that is both laminated and radially organized, as opposed to the brain of birds and reptiles. In this article, we will advance a developmental hypothesis in which the mechanisms of evolutionary brain growth remain partly conserved across amniotes (mammals, reptiles and birds), all based on Pax6 signaling or related morphogens. Despite this conservatism, only in mammals there is an additional upregulation of dorsal and anterior signaling centers (the cortical hem and the anterior forebrain, respectively) that promoted a laminar and a columnar structure into the neocortex. It is possible that independently, some birds also developed an upregulated dorsal pallium.
    Full-text · Article · Oct 2015 · Frontiers in Neuroscience
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    Conrado A Bosman · Francisco Aboitiz
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    ABSTRACT: Regardless of major anatomical and neurodevelopmental differences, the vertebrate isocortex shows a remarkably well-conserved organization. In the isocortex, reciprocal connections between excitatory and inhibitory neurons are distributed across multiple layers, encompassing modular, dynamical and recurrent functional networks during information processing. These dynamical brain networks are often organized in neuronal assemblies interacting through rhythmic phase relationships. Accordingly, these oscillatory interactions are observed across multiple brain scale levels, and they are associated with several sensory, motor, and cognitive processes. Most notably, oscillatory interactions are also found in the complete spectrum of vertebrates. Yet, it is unknown why this functional organization is so well conserved in evolution. In this perspective, we propose some ideas about how functional requirements of the isocortex can account for the evolutionary stability observed in microcircuits across vertebrates. We argue that isocortex architectures represent canonical microcircuits resulting from: (i) the early selection of neuronal architectures based on the oscillatory excitatory-inhibitory balance, which lead to the implementation of compartmentalized oscillations and (ii) the subsequent emergence of inferential coding strategies (predictive coding), which are able to expand computational capacities. We also argue that these functional constraints may be the result of several advantages that oscillatory activity contributes to brain network processes, such as information transmission and code reliability. In this manner, similarities in mesoscale brain circuitry and input-output organization between different vertebrate groups may reflect evolutionary constraints imposed by these functional requirements, which may or may not be traceable to a common ancestor.
    Full-text · Article · Oct 2015 · Frontiers in Neuroscience
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    Full-text · Conference Paper · Jun 2015
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    ABSTRACT: People with schizophrenia show social impairments that are related to functional outcomes. We tested the hypothesis that social interaction impairments in people with schizophrenia are related to alterations in the predictions of others' behavior and explored their underlying neurobiological mechanisms. Electroencephalography was performed in 20 patients with schizophrenia and 25 well-matched control subjects. Participants played as proposers in the repeated version of the Ultimatum Game believing that they were playing with another human or with a computer. The power of oscillatory brain activity was obtained by means of the wavelet transform. We performed a trial-by-trial correlation between the oscillatory activity and the risk of the offer. Control subjects adapted their offers when playing with computers and tended to maintain their offers when playing with humans, as such revealing learning and bargaining strategies, respectively. People with schizophrenia presented the opposite pattern of behavior in both games. During the anticipation of others' responses, the power of alpha oscillations correlated with the risk of the offers made, in a different way in both games. Patients with schizophrenia presented a greater correlation in computer games than in human games; control subjects showed the opposite pattern. The alpha activity correlated with positive symptoms. Our results reveal an alteration in social interaction in patients with schizophrenia that is related to oscillatory brain activity, suggesting maladjustment of expectation when patients face social and nonsocial agents. This alteration is related to psychotic symptoms and could guide further therapies for improving social functioning in patients with schizophrenia. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Feb 2015 · Biological psychiatry
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    ABSTRACT: Prenatal stress causes predisposition to cognitive and emotional disturbances and is a risk factor towards the development of neuropsychiatric conditions like depression, bipolar disorders and schizophrenia. The extracellular protein Reelin, expressed by Cajal-Retzius cells during cortical development, plays critical roles on cortical lamination and synaptic maturation, and its deregulation has been associated with maladaptive conditions. In the present study, we address the effect of prenatal restraint stress (PNS) upon Reelin expression and signaling in pregnant rats during the last 10 days of pregnancy. Animals from one group, including control and PNS exposed fetuses, were sacrificed and analyzed using immunohistochemical, biochemical, cell biology and molecular biology approaches. We scored changes in the expression of Reelin, its signaling pathway and in the methylation of its promoter. A second group included control and PNS exposed animals maintained until young adulthood for behavioral studies. Using the optical dissector, we show decreased numbers of Reelin-positive neurons in cortical layer I of PNS exposed animals. In addition, neurons from PNS exposed animals display decreased Reelin expression that is paralleled by changes in components of the Reelin-signaling cascade, both in vivo and in vitro. Furthermore, PNS induced changes in the DNA methylation levels of the Reelin promoter in culture and in histological samples. PNS adult rats display excessive spontaneous locomotor activity, high anxiety levels and problems of learning and memory consolidation. No significant visuo-spatial memory impairment was detected on the Morris water maze. These results highlight the effects of prenatal stress on the Cajal-Retzius neuronal population, and the persistence of behavioral consequences using this treatment in adults, thereby supporting a relevant role of PNS in the genesis of neuropsychiatric diseases. We also propose an in vitro model that can yield new insights on the molecular mechanisms behind the effects of prenatal stress.
    Full-text · Article · Feb 2015 · PLoS ONE

  • No preview · Conference Paper · Feb 2015
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    ABSTRACT: Intra-individual variability of response times (RTisv) is considered as potential endophe-notype for attentional deficit/hyperactivity disorder (ADHD). Traditional methods for esti-mating RTisv lose information regarding response times (RTs) distribution along the task, with eventual effects on statistical power. Ex-Gaussian analysis captures the dynamic nature of RTisv, estimating normal and exponential components for RT distribution, with specific phenomenological correlates. Here, we applied ex-Gaussian analysis to explore whether intra-individual variability of RTs agrees with criteria proposed by Gottesman and Gould for endophenotypes. Specifically, we evaluated if normal and/or exponential com-ponents of RTs may (a) present the stair-like distribution expected for endophenotypes (ADHD > siblings > typically developing children (TD) without familiar history of ADHD) and (b) represent a phenotypic correlate for previously described genetic risk variants. This is a pilot study including 55 subjects (20 ADHD-discordant sibling-pairs and 15 TD children), all aged between 8 and 13 years. Participants resolved a visual Go/Nogo with 10% Nogo probability. Ex-Gaussian distributions were fitted to individual RT data and compared among the three samples. In order to test whether intra-individual variability may represent a cor-relate for previously described genetic risk variants, VNTRs at DRD4 and SLC6A3 were identified in all sibling-pairs following standard protocols. Groups were compared adjust-ing independent general linear models for the exponential and normal components from the ex-Gaussian analysis. Identified trends were confirmed by the non-parametric Jonckheere– Terpstra test. Stair-like distributions were observed for µ (p = 0.036) and σ (p = 0.009). An additional "DRD4-genotype" × "clinical status" interaction was present for τ (p = 0.014) reflecting a possible severity factor. Thus, normal and exponential RTisv components are suitable as ADHD endophenotypes.
    Full-text · Article · Jan 2015 · Frontiers in Psychiatry
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    ABSTRACT: Solving demanding tasks requires fast and flexible coordination among different brain areas. Everyday examples of this are the social dilemmas in which goals tend to clash, requiring one to weigh alternative courses of action in limited time. In spite of this fact, there are few studies that directly address the dynamics of flexible brain network integration during social interaction. To study the preceding, we carried out EEG recordings while subjects played a repeated version of the Ultimatum Game in both human (social) and computer (non-social) conditions. We found phase synchrony (inter-site-phase-clustering) modulation in alpha band that was specific to the human condition and independent of power modulation. The strength and patterns of the inter-site-phase-clustering of the cortical networks were also modulated, and these modulations were mainly in frontal and parietal regions. Moreover, changes in the individuals' alpha network structure correlated with the risk of the offers made only in social conditions. This correlation was independent of changes in power and inter-site-phase-clustering strength. Our results indicate that, when subjects believe they are participating in a social interaction, a specific modulation of functional cortical networks in alpha band takes place, suggesting that phase synchrony of alpha oscillations could serve as a mechanism by which different brain areas flexibly interact in order to adapt ongoing behavior in socially demanding contexts.
    Full-text · Article · Oct 2014 · PLoS ONE
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    Ricardo R García · Francisco Zamorano · Francisco Aboitiz
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    ABSTRACT: The capacity for language is arguably the most remarkable innovation of the human brain. A relatively recent interpretation prescribes that part of the language-related circuits were co-opted from circuitry involved in hand control-the mirror neuron system (MNS), involved both in the perception and in the execution of voluntary grasping actions. A less radical view is that in early humans, communication was opportunistic and multimodal, using signs, vocalizations or whatever means available to transmit social information. However, one point that is not yet clear under either perspective is how learned communication acquired a semantic property thereby allowing us to name objects and eventually describe our surrounding environment. Here we suggest a scenario involving both manual gestures and learned vocalizations that led to the development of a primitive form of conventionalized reference. This proposal is based on comparative evidence gathered from other species and on neurolinguistic evidence in humans, which points to a crucial role for vocal learning in the early development of language. Firstly, the capacity to direct the attention of others to a common object may have been crucial for developing a consensual referential system. Pointing, which is a ritualized grasping gesture, may have been crucial to this end. Vocalizations also served to generate joint attention among conversants, especially when combined with gaze direction. Another contributing element was the development of pantomimic actions resembling events or animals. In conjunction with this mimicry, the development of plastic neural circuits that support complex, learned vocalizations was probably a significant factor in the evolution of conventionalized semantics in our species. Thus, vocal imitations of sounds, as in onomatopoeias (words whose sound resembles their meaning), are possibly supported by mirror system circuits, and may have been relevant in the acquisition of early meanings.
    Full-text · Article · Aug 2014 · Frontiers in Human Neuroscience
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    ABSTRACT: Prenatal stress is a risk factor for the development of neuropsychiatric disorders, many of which are commonly characterized by an increased persistence of aversive remote memory. Here, we addressed the effect of prenatal stress on both memory consolidation and functional connectivity in the hippocampal-prefrontal cortex axis, a dynamical interplay that is critical for mnemonic processing. Pregnant mice of the C57BL6 strain were subjected to restraint stressed during the last week of pregnancy, and male offspring were behaviorally tested at adulthood for recent and remote spatial memory performance in the Barnes Maze test under an aversive context. Prenatal stress did not affect the acquisition or recall of recent memory. In contrast, it produced the persistence of remote spatial memory. Memory persistence was not associated with alterations in major network rhythms, such as hippocampal sharp-wave ripples (SWRs) or neocortical spindles. Instead, it was associated with a large decrease in the basal discharge activity of identified principal neurons in the medial prefrontal cortex (mPFC) as measured in urethane anesthetized mice. Furthermore, functional connectivity was disrupted, as the temporal coupling between neuronal discharge in the mPFC and hippocampal SWRs was decreased by prenatal stress. These results could be relevant to understand the biological basis of the persistence of aversive remote memories in stress-related disorders.
    No preview · Article · May 2014 · Cerebral Cortex
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    ABSTRACT: A cardinal symptom of attention deficit and hyperactivity disorder (ADHD) is a general distractibility where children and adults shift their attentional focus to stimuli that are irrelevant to the ongoing behavior. This has been attributed to a deficit in dopaminergic signaling in cortico-striatal networks that regulate goal-directed behavior. Furthermore, recent imaging evidence points to an impairment of large scale, antagonistic brain networks that normally contribute to attentional engagement and disengagement, such as the task-positive networks and the default mode network (DMN). Related networks are the ventral attentional network (VAN) involved in attentional shifting, and the salience network (SN) related to task expectancy. Here we discuss the tonic-phasic dynamics of catecholaminergic signaling in the brain, and attempt to provide a link between this and the activities of the large-scale cortical networks that regulate behavior. More specifically, we propose that a disbalance of tonic catecholamine levels during task performance produces an emphasis of phasic signaling and increased excitability of the VAN, yielding distractibility symptoms. Likewise, immaturity of the SN may relate to abnormal tonic signaling and an incapacity to build up a proper executive system during task performance. We discuss different lines of evidence including pharmacology, brain imaging and electrophysiology, that are consistent with our proposal. Finally, restoring the pharmacodynamics of catecholaminergic signaling seems crucial to alleviate ADHD symptoms; however, the possibility is open to explore cognitive rehabilitation strategies to top-down modulate network dynamics compensating the pharmacological deficits.
    Full-text · Article · Mar 2014 · Frontiers in Psychology
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    ABSTRACT: During social bargain, one has to both figure out the others' intentions and behave strategically in such a way that the others' behaviors will be consistent with one's expectations. To understand the neurobiological mechanisms underlying these behaviors, we used electroencephalography while subjects played as proposers in a repeated Ultimatum Game. We found that subjects adapted their offers in order to obtain more acceptances in the last round and that this adaptation correlated negatively with prefrontal theta oscillations. People with higher prefrontal theta activity related to a rejection did not adapt their offers along the game to maximize their earning. Moreover, between-subject variation in posterior theta oscillations correlated positively with how individual theta activity influenced the change of offer after a rejection, reflecting a process of behavioral adaptation to the others' demands. Interestingly, people adapted better their offers when they knew that they where playing against a computer, although the behavioral adaptation did not correlate with prefrontal theta oscillation. Behavioral changes between human and computer games correlated with prefrontal theta activity, suggesting that low adaptation in human games could be a strategy. Taken together, these results provide evidence for specific roles of prefrontal and posterior theta oscillations in social bargaining.
    Full-text · Article · Feb 2014 · Social Cognitive and Affective Neuroscience
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    ABSTRACT: The capacity to inhibit prepotent and automatic responses is crucial for proper cognitive and social development, and inhibitory impairments have been considered to be key for some neuropsychiatric conditions. One of the most used paradigms to analyze inhibitory processes is the Go-Nogo task (GNG). This task has been widely used in psychophysical and cognitive EEG studies, and more recently in paradigms using fMRI. However, a technical limitation is that the time resolution of fMRI is poorer than that of the EEG technique. In order to compensate for these temporal constraints, it has become common practice in the fMRI field to use longer inter-stimulus intervals (ISI) than those used in EEG protocols. Despite the noticeable temporal differences between these two techniques, it is currently assumed that both approaches assess similar inhibitory processes. We performed an EEG study using a GNG task with both short ISI (fast-condition, FC, as in EEG protocols) and long ISI (slow-condition, SC, as in fMRI protocols). We found that in the FC there was a stronger Nogo-N2 effect than in the SC. Moreover, in the FC, but not in the SC, the number of preceding Go trials correlated positively with the Nogo-P3 amplitude and with the Go trial reaction time; and negatively with commission errors. In addition, we found significant topographical differences for the Go-P3 elicited in FC and SC, which is interpreted in terms of different neurotransmitter dynamics. Taken together, our results provide evidence that frequency of stimulus presentation in the GNG task strongly modulates the behavioral response and the evoked EEG activity. Therefore, it is likely that short-ISI EEG protocols and long-ISI fMRI protocols do not assess equivalent inhibitory processes.
    Full-text · Article · Jan 2014 · PLoS ONE
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    Francisco Aboitiz · Francisco Zamorano
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    ABSTRACT: The anatomical organization of the mammalian neocortex stands out among vertebrates for its laminar and columnar arrangement, featuring vertically oriented, excitatory pyramidal neurons. The evolutionary origin of this structure is discussed here in relation to the brain organization of other amniotes, i.e., the sauropsids (reptiles and birds). Specifically, we address the developmental modifications that had to take place to generate the neocortex, and to what extent these modifications were shared by other amniote lineages or can be considered unique to mammals. In this article, we propose a hypothesis that combines the control of proliferation in neural progenitor pools with the specification of regional morphogenetic gradients, yielding different anatomical results by virtue of the differential modulation of these processes in each lineage. Thus, there is a highly conserved genetic and developmental battery that becomes modulated in different directions according to specific selective pressures. In the case of early mammals, ecological conditions like nocturnal habits and reproductive strategies are considered to have played a key role in the selection of the particular brain patterning mechanisms that led to the origin of the neocortex.
    Full-text · Article · Nov 2013 · Frontiers in Neuroanatomy
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    Enzo Brunetti · Pedro E Maldonado · Francisco Aboitiz
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    ABSTRACT: During monitoring of the discourse, the detection of the relevance of incoming lexical information could be critical for its incorporation to update mental representations in memory. Because, in these situations, the relevance for lexical information is defined by abstract rules that are maintained in memory, a central aspect to elucidate is how an abstract level of knowledge maintained in mind mediates the detection of the lower-level semantic information. In the present study, we propose that neuronal oscillations participate in the detection of relevant lexical information, based on "kept in mind" rules deriving from more abstract semantic information. We tested our hypothesis using an experimental paradigm that restricted the detection of relevance to inferences based on explicit information, thus controlling for ambiguities derived from implicit aspects. We used a categorization task, in which the semantic relevance was previously defined based on the congruency between a kept in mind category (abstract knowledge), and the lexical semantic information presented. Our results show that during the detection of the relevant lexical information, phase synchronization of neuronal oscillations selectively increases in delta and theta frequency bands during the interval of semantic analysis. These increments occurred irrespective of the semantic category maintained in memory, had a temporal profile specific for each subject, and were mainly induced, as they had no effect on the evoked mean global field power. Also, recruitment of an increased number of pairs of electrodes was a robust observation during the detection of semantic contingent words. These results are consistent with the notion that the detection of relevant lexical information based on a particular semantic rule, could be mediated by increasing the global phase synchronization of neuronal oscillations, which may contribute to the recruitment of an extended number of cortical regions.
    Full-text · Article · Jun 2013 · Frontiers in Psychology
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    ABSTRACT: Converging neuroscientific evidence suggests the existence of close links between language and sensorimotor cognition. Accordingly, during the comprehension of meaningful actions, our brain would recruit semantic-related operations similar to those associated with the processing of language information. Consistent with this view, electrophysiological findings show that the N400 component, traditionally linked to the semantic processing of linguistic material, can also be elicited by action-related material. This review outlines recent data from N400 studies that examine the understanding of action events. We focus on three specific domains, including everyday action comprehension, co-speech gesture integration, and the semantics involved in motor planning and execution. Based on the reviewed findings, we suggest that both negativities (the N400 and the action-N400) reflect a common neurocognitive mechanism involved in the construction of meaning through the expectancies created by previous experiences and current contextual information. To shed light on how this process is instantiated in the brain, a testable contextual fronto-temporo-parietal model is proposed.
    Full-text · Article · Mar 2013 · Frontiers in Human Neuroscience

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